Abstract
Background
Bojungikki-tang (Buzhongyiqi decoction, Hochuekkito, BIT) has been used in East Asian medicine for conditions with fatigue, reduced appetite, and functional decline. In recent years, research on this preparation has expanded across diverse disease areas, yet its contemporary evidence landscape has not been systematically mapped. This scoping review aimed to characterize the scope, methodological features, outcome domains, botanical drug reporting, and safety reporting of studies published since 2015.
Methods
A comprehensive search of PubMed, Embase, CENTRAL, and OASIS was conducted to identify studies evaluating BIT. Eligible studies included randomized controlled trials non-randomized trials, observational studies, and case-based reports published from 2015 onward. Data were charted on study design, disease system, intervention characteristics, botanical composition, formulation reporting, outcome domains, and adverse-event reporting, and synthesized descriptively.
Results
Forty-seven studies involving 2,568 participants were included. RCTs accounted for 48.9%, while case-based studies comprised 27.7%. Oncology represented the largest disease cluster (27.7%), followed by urogenital (17.0%), neurologic (14.9%), and respiratory conditions (12.8%). BIT was used as monotherapy in 55.3% of studies and as an adjunct in 44.7%. Granule and decoction forms accounted for 89.4% of interventions. Outcomes assessed fatigue, appetite, quality of life, functional recovery, inflammatory and nutritional biomarkers, and treatment tolerance. Heterogeneity in formulation, comparators, outcomes, and safety reporting limited comparability.
Conclusion
Recent studies suggest that BIT is investigated as a recovery-oriented intervention in conditions with immune–inflammatory stress and functional vulnerability. Greater standardization in botanical drug nomenclature, formulation definition, outcome frameworks, and harms reporting is needed for evidence-based botanical drug research.
Keywords: Bojungikki-tang, botanical drug, Buzhongyiqi decoction, clinical evidence, Hochuekkito
1. Background
Bojungikki-tang (also known as Hochu-ekki-to or Buzhong Yiqi Decoction, BIT) is a classical East Asian multi-botanical preparation traditionally prescribed for states of reduced vitality characterized by fatigue, diminished appetite, and impaired recovery capacity. It is a multi-botanical preparation traditionally composed of Astragali Radix, Ginseng Radix, and other supporting botanical drugs, and is used to strengthen digestive function and promote systemic restoration during deficiency conditions (Hu et al., 2024). Its continued use across Korean Medicine, Chinese medicine, and Japanese Kampo medicine makes BIT a representative traditional East Asian multi-botanical preparation for examining how long-standing clinical use is being translated into contemporary human research. Because the preparation is commonly chosen to improve functional status rather than target a single disease entity, it has been applied across a wide range of clinical settings, including postoperative recovery, frailty-related syndromes, and supportive management of chronic illnesses (Hu et al., 2024; Kim et al., 2017; Guo et al., 2022). While this broad applicability has contributed to its sustained clinical relevance, it has also blurred the boundaries of its most evidence-supported indications, creating challenges for both clinical interpretation and research synthesis.
Despite widespread clinical use, routine decision-making surrounding BIT continues to depend largely on traditional indications and practitioner experience rather than clearly defined, evidence-based clinical contexts. Studies in older or frail populations have reported improvements in patient-centered outcomes such as quality of life and immune-related parameters, supporting a potential role in deficiency-related conditions (Satoh et al., 2005; Kuroiwa et al., 2004). More recent controlled studies have explored recovery, appetite, and activity outcomes in postoperative settings, again pointing toward functional benefits that matter to patients and caregivers (Watanabe and Maeda, 2022; Okugawa et al., 2024). Nevertheless, much of the existing evidence remains condition-specific, limited in scale, or confined to single healthcare systems, leaving clinicians without an integrated understanding of studied populations, BIT formulation variations, comparators, and outcome priorities.
An additional challenge arises from the fragmented and condition-specific nature of the existing clinical literature, much of which is limited by small sample sizes, heterogeneous designs, variable methodological quality, and a relative lack of rigorously conducted randomized controlled trials (RCTs), resulting in an insufficient body of high-quality integrated evidence. Evidence syntheses in selected disease areas demonstrate both therapeutic promise and methodological limitations. Meta-analytic findings in stable chronic obstructive pulmonary disease (COPD) indicate potential improvements in respiratory function, exercise tolerance, and quality of life, while consistently highlighting the need for more rigorous RCTs (Chen et al., 2016; Kwon et al., 2021). Similarly, pooled analyses in functional constipation suggest symptomatic benefit but are constrained by heterogeneity and variable study quality (Gong et al., 2018). Together, these findings reflect sustained clinical interest in BIT while underscoring the absence of a comprehensive, clinically oriented synthesis of human research evidence.
This scoping review aims to assemble an up-to-date, clinically oriented picture of how BIT has been studied in humans and where research activity is most concentrated. The goal is to summarize current clinical applications across diseases and age groups, identify which study designs dominate the landscape, and clarify how botanical drug composition, formulation types, comparators, safety reporting, and outcome measures vary in practice. This approach is particularly relevant because BIT is not a single standardized product, but a traditional multi-botanical preparation used in fixed commercial granules, decoctions, powders, pills, and modified prescriptions. By highlighting areas with repeated controlled testing alongside areas still supported mainly by exploratory clinical studies, the review will help clinicians interpret existing findings with appropriate caution and help researchers pinpoint feasible, high-impact questions for future controlled trials.
2. Methods
2.1. Study design and framework
This scoping review was designed based on the methodological framework originally proposed by Arksey and O’Malley (Arksey and O’Malley, 2005; Tricco et al., 2018), with additional guidance drawn from the Joanna Briggs Institute approach to strengthen methodological rigor (Peters et al., 2020). The reporting of the review followed the PRISMA Extension for Scoping Reviews (PRISMA-ScR) to ensure transparent and systematic presentation of the evidence identification and selection process. The protocol was prospectively registered on the Open Science Framework (OSF; https://osf.io/vphtm/overview; registered 23 September 2025). The review seeks to comprehensively map the clinical research landscape of BIT by summarizing study characteristics, populations, interventions, comparators, and outcome measures, thereby supporting future evidence synthesis and targeted clinical research planning. Consistent with scoping review methodology, formal risk-of-bias assessment was not conducted, as the purpose was to map the evidence rather than synthesize effect estimates.
2.2. Definition of preparations and taxonomic validation
BIT and its modified formulations evaluated in this review were defined as oral traditional East Asian multi-botanical preparations rather than a single standardized product. Botanical drug names were extracted as reported in the original studies, and full species names, author citations, family names, medicinal parts, and pharmacopeial drug names were standardized where identifiable in accordance with ConPhyMP recommendations and best-practice guidance for ethnopharmacological research (Heinrich et al., 2022; Rivera et al., 2014). Taxonomic validation was conducted using Plants of the World Online (Kew, https://powo.science.kew.org/) and Medicinal Plant Names Services (MPNS, https://mpns.kew.org). Because this study is a scoping review of published clinical studies, extraction methods, processing procedures, manufacturing conditions, batch information, certificates of analysis, and regulatory status were recorded only when reported in the original studies. The taxonomically validated botanical drug composition and other medicinal materials included in modified formulations are summarized in Supplementary Table S2.
2.3. Research questions
The review addresses the following questions: (1) To what extent has BIT been investigated in clinical research published since 2015, and across what populations (including disease categories, age groups, and geographic regions) and research designs (including case series, non-RCTs, and RCTs)? (2) What BIT formulations, comparators, and outcome measures have been used, and what recurring clinical clusters and intervention–outcome patterns can be identified to inform future evidence synthesis and clinical trial planning?
2.4. Eligibility criteria
Studies were included if they met the following criteria: (1) involved human participants without restrictions on age, disease category, or geographic location; (2) evaluated BIT as the primary intervention regardless of formulation type, preparation method, or modification; and (3) were published in peer-reviewed journals from January 2015 through December 2025. This time window was selected a priori to capture recent clinical use of BIT and contemporary standards in clinical trial design, intervention reporting, and safety reporting. All clinical study designs involving human subjects were considered eligible, including observational studies and controlled clinical trials. Studies were excluded if they met any of the following conditions: (1) non-human experimental research, including in vitro or animal studies; (2) study protocols, review articles, conference abstracts without full-text availability, or other non-original research; or (3) publications released prior to 2015.
2.5. Information sources and search strategy
A systematic search was conducted across PubMed, Embase, CENTRAL, and OASIS to capture both international biomedical literature and traditional medicine–focused publications relevant to BIT. The database search was performed on 16 December 2025. Search strategies incorporated a combination of controlled vocabulary terms and free-text keywords reflecting the formula and its commonly used variants. Representative search terms included “Bojungikki-tang,” “Bojungikgi-tang,” “Bu Zhong Yi Qi Tang,” “Buzhong Yiqi,” “Hochu-ekki-to,” “Hochuekkito,” and “TJ-41,” among others. These terms were adapted to the syntax of each database and combined using appropriate Boolean operators. No language restrictions were applied during the database search. Full-text articles were assessed when accessible, regardless of publication language. No additional manual reference screening was conducted beyond the predefined database search. The complete database-specific search strategies and full search strings are provided in Supplementary Table S1.
2.6. Study selection
All records retrieved from the database searches were imported into EndNote for reference management and duplicate removal. Two independent reviewers screened titles and abstracts according to the predefined eligibility criteria, followed by full-text assessment of potentially relevant studies. Discrepancies between reviewers were resolved through discussion, and when necessary, by consulting a third reviewer. The study selection process is presented using a PRISMA flow diagram, detailing the number of records identified, screened, included, and excluded, along with reasons for exclusion at each stage.
2.7. Data extraction and synthesis
Data extraction was independently performed by two reviewers using a standardized form developed a priori to ensure methodological consistency. Extracted information included author and publication year, country of study, study design, disease or condition investigated, mean or median participant age, formulation of BIT including dosage form and modifications, botanical drug composition, preparation or extraction information where available, commercial product information where available, concomitant medications or co-interventions, adverse-event reporting, interaction-related safety information, comparator type (if applicable), outcome measures, and key findings. Any disagreements during data extraction were resolved through discussion or, if required, by consultation with a third reviewer. For descriptive synthesis, BIT interventions were categorized by formulation type, modification status, and treatment role. Standardized BIT formulations were defined as fixed commercial products or fixed-dose preparations without patient-specific modification, whereas modified BIT formulations were defined as prescriptions in which botanical drugs were added, removed, or adjusted according to disease characteristics or patient presentation. BIT was also classified as monotherapy or adjunctive therapy according to whether it was used alone or in combination with conventional treatment, rehabilitation, acupuncture, pharmacopuncture, or other co-interventions. Outcome measures were grouped into patient-reported outcomes, functional measures, laboratory or biomarker outcomes, microbiologic or microbiome-related outcomes, treatment response outcomes, and safety outcomes. Frequency analyses were conducted to summarize the distribution of study designs, clinical indications, formulation types, comparator categories, and outcome domains. Narrative summaries complemented the descriptive findings to identify recurring research patterns and gaps within the clinical literature, thereby enabling systematic mapping of the evidence landscape.
3. Results
3.1. Study selection
The database search yielded 667 records, including 222 from PubMed, 302 from Embase, 127 from CENTRAL, and 16 from OASIS. After removal of 229 duplicates, 438 records remained for title and abstract screening. Among these, 388 studies were excluded, including those not related to BIT (n = 73), non-clinical research (n = 139), duplicate publications (n = 32), review articles or study protocols (n = 130), and studies without available full text (n = 14). Fifty full-text articles were assessed for eligibility, of which three were excluded due to pharmacokinetic focus without clinical outcome evaluation. Ultimately, 47 clinical studies were included in the scoping review (Figure 1).
FIGURE 1.
PRISMA study flow chart.
3.2. Characteristics of included studies
3.2.1. Study design and geographic distribution
The 47 included studies involved a total of 2,568 participants. RCTs comprised 23 studies (48.9%) (Akita et al., 2019; Chen et al., 2024; Chen et al., 2018; Edahiro et al., 2022; Hamada et al., 2018; Hamada et al., 2022; Huang, 2015; Ko et al., 2025; Lee et al., 2025; Lee et al., 2024; Li et al., 2016; Lu et al., 2021; Okabe et al., 2019; Qian et al., 2024; Teng et al., 2016; Terai et al., 2020; Wang, 2016; Wang et al., 2021; Watanabe and Maeda, 2022; Wu et al., 2017; Xu et al., 2023; Yang, 2016; Zhang and Zhu, 2015), followed by case-based studies including case reports and case series (13 studies, 27.7%) (Kim et al., 2023; Kim and Keum, 2015; Lee et al., 2021; Lee et al., 2015; Lee et al., 2018; Lee, 2017; Lee et al., 2019; Li et al., 2021a; Minagawa et al., 2019; Park et al., 2025; Qiu et al., 2024; Seo et al., 2019; Takeuchi et al., 2017). Observational studies accounted for 9 studies (19.1%), consisting of 3 prospective and 6 retrospective designs (Hu et al., 2024; Huang et al., 2025; Kitahara et al., 2021; Kohno et al., 2021; Li et al., 2021b; Ni et al., 2021; Oh et al., 2023; Okugawa et al., 2024; Tokumasu et al., 2025). Only 2 studies (4.3%) employed non-RCT designs (Kim et al., 2024; Zhou et al., 2022). Geographically, China contributed 20 studies (42.6%), South Korea 13 studies (27.7%), Japan 13 studies (27.7%), and Taiwan 1 study (2.1%). RCTs were predominantly conducted in China and Japan, whereas case-based studies were more frequently reported in South Korea. Most studies were conducted in hospital-based settings, including 25 single-center hospital studies (53.2%) and 14 multicenter hospital studies (29.8%), while 7 studies (14.9%) were conducted in single-center clinic or community clinic settings and 1 study (2.1%) involved a mixed multicenter clinic/hospital setting. Funding sources were variably reported, with 21 studies (44.7%) reporting government or public funding, 2 studies (4.3%) reporting combined government/public and company funding, 4 studies (8.5%) reporting company funding, 2 studies (4.3%) reporting no funding, and 18 studies (38.3%) not reporting funding sources (Table 1).
TABLE 1.
Characteristics of included clinical studies on Bojungikki-tang.
| Study ID | Country | Study setting | Study design | Disease/Condition | Disease system | Sample size | Age (year) | Funding source |
|---|---|---|---|---|---|---|---|---|
| Akita et al. (2019) | Japan | Multicenter hospital | RCT | Chronic refractory wounds | Surgery | TG: 9/CG: 9 | TG: 50/CG: 54 | NR |
| Chen et al. (2024) | China | Single-center hospital | RCT | Postartum stress urinary incontinence (PSUI) | Urogenital | TG: 128/CG: 128 | TG 27.83 ± 5.52/CG 27.81 ± 5.46 | Government/public funding |
| Chen et al. (2018) | China | Single-center hospital | RCT | Early postpartum pelvic floor dysfunction (PFD) | Urogenital | TG: 93/CG: 93 | TG 24.63 ± 2.05/CG 24.18 ± 2.12 | NR |
| Edahiro et al. (2022) | Japan | Multicenter hospital | RCT | Myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, myelofibrosis) | Cancer | TG: 21/CG: 21 | TG: 65 (IQR 50–71)/CG: 62 (IQR 56–65) | NR |
| Hamada et al. (2018) | Japan | Multicenter hospital | RCT | Chronic obstructive pulmonary disease (COPD) | Respiratory | TG: 18/CG: 15 | TG: 75.3 ± 6.1/CG: 74.7 ± 7.1 | Government/public + company |
| Hamada et al. (2022) | Japan | Multicenter hospital | RCT | COPD with apathy (mild depression excluded) | Respiratory | TG: 11/CG: 12 | TG 72.5 ± 5.7/CG 76.4 ± 7.1 | Government/public + company |
| Hu et al. (2024) | China | Single-center hospital | Retrospective observational study | Colorectal cancer after neoadjuvant chemotherapy and laparoscopic radical surgery with spleen-stomach qi deficiency | Cancer | TG: 50/CG: 50 | TG 46.97 ± 14.21/CG 47.12 ± 13.37 | NR |
| Huang (2015) | China | Single-center hospital | RCT | Type 2 diabetes mellitus | Metabolic | TG: 63/CG: 63 | 53.4 ± 3.2 | NR |
| Huang et al. (2025) | China | Single-center hospital | Prospective observational study | Obstructive sleep apnea (OSA) with lung-spleen Qi deficiency | Respiratory | 11 | 40.5 ± 10.2 | Government/public funding |
| Kim et al. (2023) | South Korea | Single-center hospital | Case report | Postherpetic neuralgia | Neurologic | 1 | 77 | NR |
| Kim et al. (2024) | South Korea | Single-center hospital | Non-RCT | Long COVID (fatigue/Cognitive dysfunction) | Respiratory | BIT: 15/KOG: 15/CBD: 15 | BIT: 43.80 ± 14.31/KOG: 45.33 ± 12.57/CBD: 51.33 ± 15.71 | Government/public funding |
| Kim and Keum (2015) | South Korea | Single-center clinic | Case series | Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) | Urogenital | 11 | 48.9 ± 10.1 (34–63) | NR |
| Kitahara et al. (2021) | Japan | Single-center hospital | Retrospective observational study | MRSA colonization in acute stroke patients | Neurologic | TG: 41/CG: 32 | BIT: 83.0 ± 9.2/Control: 82.2 ± 10.2 | Company funding |
| Ko et al. (2025) | South Korea | Multicenter hospital | RCT | Advanced non-small-cell lung cancer (NSCLC) patients receiving atezolizumab | Cancer | TG: 14/CG: 14 | TG: 73.36 ± 8.14/CG: 71.71 ± 7.98 | Government/public funding |
| Kohno et al. (2021) | Japan | Multicenter hospital | Retrospective observational study | Vancomycin-resistant enterococci (VRE) colonization | Immune | TG: 16/CG: 106 | TG: 69.9 ± 17.5/CG: 72.6 ± 12.2 | Government/public funding |
| Lee et al. (2025) | South Korea | Single-center hospital | RCT | Anorexia in adults with atopic dermatitis | Immune | TG: 12/CG: 12 | TG: 28.83 (95% CI: 25.43–32.24)/CG: 32.58 (95% CI: 23.37–41.80) | Government/public funding |
| Lee et al. (2021) | South Korea | Single-center clinic | Case report | Advanced NSCLC with brain & bone metastasis | Cancer | 1 | 83 | Government/public funding |
| Lee et al. (2015) | South Korea | Single-center hospital | Case report | Cervical cancer-related fatigue after concurrent chemoradiation therapy | Cancer | 1 | 68 | Government/public funding |
| Lee et al. (2018) | Taiwan | Single-center hospital | Case report | Multiple sclerosis with IFNβ-1a–induced flu-like symptoms | Neurologic | 1 | 30 | Government/public funding |
| Lee (2017) | South Korea | Single-center clinic | Case report | Chemotherapy-induced alopecia and general weakness in cholangiocarcinoma with liver metastasis | Cancer | 1 | 70 | NR |
| Lee et al. (2019) | South Korea | Single-center hospital | Case report | Sweating and palpitation after chemotherapy for primary central nervous system lymphoma | Cancer | 1 | 41 | Government/public funding |
| Lee et al. (2024) | South Korea | Single-center hospital | RCT | Persistent allergic rhinitis (PAR) | Immune | High-dose: 35/Standard-dose: 35/Placebo: 35 | High: 36.74 ± 12.78/Std: 34.74 ± 11.93/Placebo: 33.03 ± 11.47 | Government/public funding |
| Li et al. (2021a) | China | Multicenter hospital | Case report | Facioscapulohumeral muscular dystrophy (FSHD1) | Neurologic | 1 | 15 | NR |
| Li et al. (2021b) | China | Single-center hospital | Retrospective observational study | Juvenile ocular myasthenia gravis (JOMG) | Neurologic | BIT-only: 73/BIT + Pred: 33/BIT-instead: 29 | BIT-only: 4.3 ± 3.6/BIT + Pred: 4.8 ± 3.5/BIT-instead: 5.8 ± 3.3 | NR |
| Li et al. (2016) | China | Multicenter hospital | RCT | Postoperative NSCLC receiving radiochemotherapy | Cancer | TG: 40/CG: 40 | TG 55.4 ± 9.6/CG 55.2 ± 9.8 | Government/public funding |
| Lu et al. (2021) | China | Single-center hospital | RCT | Circumferential mixed hemorrhoids after PPH surgery | Surgery | TG: 60/CG: 60 | TG: 42.8 ± 2.4/CG: 43.4 ± 2.7 | NR |
| Minagawa et al. (2019) | Japan | Multicenter hospital | Case series | Cancer-related fatigue after starting enzalutamide in castration-resistant prostate cancer (CRPC) | Cancer | 3 | 72, 69, 88 (mean: 76.3) | NR |
| Ni et al. (2021) | China | Single-center hospital | Prospective observational study | Obesity with polycystic ovary syndrome (PCOS) | Metabolic | 15 | 27.6 (24–32) | Government/public funding |
| Oh et al. (2023) | South Korea | Single-center hospital | Retrospective observational study | Type 2 diabetes mellitus | Metabolic | 15 | 81.53 ± 8.06 | Government/public funding |
| Okabe et al. (2019) | Japan | Multicenter hospital | RCT | Stage II/III gastric cancer after curative resection | Cancer | TG: 55/CG: 55 | TG: 65 (49–76)/CG: 64 (35–77) | Company funding |
| Okugawa et al. (2024) | Japan | Multicenter hospital | Retrospective observational study | Gastrointestinal cancer (majority metastatic) | Cancer | TG: 56 | TG: 72.5 (66.5-81) | Company funding |
| Park et al. (2025) | South Korea | Single Korean medicine clinic | Case report | Adenomyosis | Urogenital | 1 | 40 | No funding |
| Qian et al. (2024) | China | Single-center hospital | RCT | Colorectal cancer | Cancer | BIT-placebo: 33/Placebo-BIT: 29 | TG: 59.55 ± 8.98/CG: 61.79 ± 8.99 | Government/public funding |
| Qiu et al. (2024) | China | Single-center hospital | Case report | Moderate generalized myasthenia gravis | Neurologic | 1 | 50 | Government/public funding |
| Seo et al. (2019) | South Korea | Single-center hospital | Case report | Urinary retention and dysuria after stroke | Neurologic | 1 | 89 | NR |
| Takeuchi et al. (2017) | Japan | Multicenter hospital | Case report | Late-onset hypogonadism syndrome | Urogenital | 1 | 54 | No funding |
| Teng et al. (2016) | China | Single-center clinic | RCT | Perimenopausal uterine bleeding | Urogenital | TG: 38/CG: 33 | 40–50 | NR |
| Terai et al. (2020) | Japan | Multicenter clinic/hospital | RCT | Idiopathic male infertility | Urogenital | TG: 16/CG: 15 | TG: 39.8 ± 5.8/CG: 39.4 ± 6.8 | NR |
| Tokumasu et al. (2025) | Japan | Single-center hospital | Prospective observational study | Long COVID/Post-COVID-19 condition with general fatigue | Respiratory | 20 | 42.9 ± 15.8 | Government/public funding |
| Wang (2016) | China | Single-center community clinic | RCT | Postprandial fullness/dyspepsia-like symptoms | Gastrointestinal | TG: 35/CG: 35 | NR | NR |
| Wang et al. (2021) | China | Multicenter hospital | RCT | Non–muscle-invasive bladder cancer after transurethral resection of bladder tumor (TURBT) | Cancer | TG: 35/CG: 35 | TG: NR/CG: NR | NR |
| Watanabe and Maeda (2022) | Japan | Single-center hospital | RCT | Postoperative hip fracture (elderly) | Surgery | TG: 20/CG: 18 | TG: 84.4 ± 8.9/CG: 85.1 ± 8.8 | Company funding |
| Wu et al. (2017) | China | Single-center hospital | RCT | Postoperative anal fistula with food allergy | Immune | BIT: 6/Positive control: 6/Negative control: 6 | 22–65 | Government/public funding |
| Xu et al. (2023) | China | Multicenter hospital | RCT | Hospital-acquired pneumonia with MDR bacteria | Respiratory | TG: 83/CG: 85 | TG: 75.9 ± 12.3/CG: 76.5 ± 10.2 | Government/public funding |
| Yang (2016) | China | Single-center community clinic | RCT | Geriatric reflux esophagitis | Gastrointestinal | TG: 64/CG: 58 | TG: 67.1 (61-73)/CG: 65.2 (60-74) | NR |
| Zhang and Zhu (2015) | China | Single-center hospital | RCT | Cervical lesions post-, loop electrosurgical excision procedure (LEEP) | Surgery | TG: 30/CG: 30 | TG: 38.29 ± 6.28/CG: 37.86 ± 7.86 | Government/public funding |
| Zhou et al. (2022) | China | Single-center hospital | Non-RCT | Female stress urinary incontinence | Urogenital | 90 | 50.0 ± 13.6 | Government/public funding |
BIT, Bojungikki-tang; CBD, Cheonwangbosim-dan; CG, control group; IQR, interquartile range; KOG, Kyungok-go; NR, not reported; RCT, randomized controlled trial; TG, treatment group.
3.2.2. Disease system distribution and clinical focus
For descriptive synthesis, indications were organized using a system-based clinical grouping approach according to the primary organ system or clinical domain involved. Cancer-related conditions represented the largest proportion of included studies, accounting for 13 studies (27.7%) (Edahiro et al., 2022; Hu et al., 2024; Ko et al., 2025; Lee et al., 2021; Lee et al., 2015; Lee, 2017; Lee et al., 2019; Li et al., 2016; Minagawa et al., 2019; Okabe et al., 2019; Okugawa et al., 2024; Qian et al., 2024; Wang et al., 2021). These investigations encompassed a broad spectrum of malignancies, including lung cancer, gastrointestinal cancers, cervical cancer, bladder cancer, and hematologic malignancies, reflecting a strong concentration of clinical research within oncology settings. Urogenital disorders comprised 8 studies (17.0%) (Chen et al., 2024; Chen et al., 2018; Kim and Keum, 2015; Park et al., 2025; Takeuchi et al., 2017; Teng et al., 2016; Terai et al., 2020; Zhou et al., 2022), followed by neurologic disorders with 7 studies (14.9%) (Kim et al., 2023; Kitahara et al., 2021; Lee et al., 2018; Li et al., 2021a; Li et al., 2021b; Qiu et al., 2024; Seo et al., 2019). Respiratory diseases were investigated in 6 studies (12.8%) (Hamada et al., 2018; Hamada et al., 2022; Huang et al., 2025; Kim et al., 2024; Tokumasu et al., 2025, Xu et al., 2023). Surgery-related conditions (Akita et al., 2019; Lu et al., 2021; Watanabe and Maeda, 2022; Zhang and Zhu, 2015) and immune-related conditions (Kohno et al., 2021; Lee et al., 2025; Lee et al., 2024; Wu et al., 2017) were each represented by 4 studies (8.5%). Metabolic disorders were examined in 3 studies (6.4%) (Huang, 2015; Ni et al., 2021; Oh et al., 2023), while gastrointestinal disorders were the least frequently studied category, comprising 2 studies (4.3%) (Wang, 2016; Yang, 2016) (Table 1; Figure 2).
FIGURE 2.
System-based mapping of clinical studies on Bojungikki-tang. RCT, randomized controlled trial.
3.3. Details in intervention characteristics
3.3.1. Mode of administration and formulation
BIT was administered either as monotherapy or in combination with other therapeutic approaches. Monotherapy was employed in 26 studies (55.3%), whereas 21 studies (44.7%) evaluated BIT as an adjunct to conventional treatments, rehabilitation programs, pharmacological therapy, or other integrative interventions. Regarding formulation, granule preparations were most frequently used, appearing in 22 studies (46.8%) (Akita et al., 2019; Edahiro et al., 2022; Hamada et al., 2018; Hamada et al., 2022; Huang et al., 2025; Kim et al., 2024; Kitahara et al., 2021; Ko et al., 2025; Kohno et al., 2021; Lee et al., 2025; Lee et al., 2015; Lee, 2017; Lee et al., 2024; Minagawa et al., 2019; Oh et al., 2023; Okabe et al., 2019; Okugawa et al., 2024; Takeuchi et al., 2017; Terai et al., 2020; Tokumasu et al., 2025; Watanabe and Maeda, 2022; Wu et al., 2017), followed closely by decoction-based prescriptions in 20 studies (42.6%) (Chen et al., 2024; Chen et al., 2018; Hu et al., 2024; Huang, 2015; Kim et al., 2023; Lee et al., 2021; Li et al., 2021a; Li et al., 2021b; Li et al., 2016; Lu et al., 2021; Ni et al., 2021; Park et al., 2025; Qiu et al., 2024; Seo et al., 2019; Teng et al., 2016; Wang, 2016; Wang et al., 2021; Xu et al., 2023; Zhang and Zhu, 2015; Zhou et al., 2022). Powder and pill formulations were less common, each reported in 2 studies (4.3%) (Kim and Keum, 2015; Lee et al., 2018; Qian et al., 2024; Yang, 2016), while one study (2.1%) utilized a mixed formulation approach combining granules and decoctions (Lee et al., 2019) (Table 2).
TABLE 2.
Characteristics of Bojungikki-tang interventions across included clinical studies.
| Study ID | Intervention | Formulation | Composition | Dosage | Frequency | Treatment duration | Comparator |
|---|---|---|---|---|---|---|---|
| Akita et al. (2019) | Bojungikki-tang | Granules | Ginseng radix, atractylodis rhizoma, astragali radix, angelicae radix, zizyphi fructus, bupleuri radix, glycyrrhizae radix, zingiberis rhizoma, cimicifugae rhizoma, aurantii nobilis pericarpium | 7.5 g/day | TID | 12 weeks | Standard care only |
| Chen et al. (2024) | Bojungikki-tang + biofeedback electrical stimulation | Decoction | Astragali radix 18 g, angelicae radix 18 g, leonuri herba 18 g, codonopsis radix 16 g, dipsaci radix 15 g, atractylodis rhizoma 12 g, cimicifugae rhizoma 12 g, bupleuri radix 12 g, aurantii nobilis pericarpium 12 g, ligustici rhizoma 12 g, amomi fructus 10 g, chebulae fructus 10 g, corni fructus 10 g, glycyrrhizae radix praeparata 8 g | 200 mL/day | BID | 8 weeks | Pelvic floor muscle rehabilitation training only |
| Chen et al. (2018) | Modified bojungikki-tang + pelvic floor muscle exercise + biofeedback + electrical stimulation | Decoction | Codonopsis pilosula 16 g, atractylodes macrocephala 12 g, cimicifuga heracleifolia 12 g, astragalus membranaceus 18 g, angelica sinensis 18 g, citrus reticulata 12 g, glycyrrhiza uralensis (honey-fried) 8 g, leonurus japonicus 18 g, ligusticum chuanxiong 12 g, dipsacus asper 15 g, cornus officinalis 10 g, terminalia chebula 10 g, alpinia oxyphylla 10 g | 150 mL/day | BID | 6 weeks | Pelvic floor muscle exercise + biofeedback + electrical stimulation only |
| Edahiro et al. (2022) | Bojungikki-tang | Granules | Astragalus membranaceus, atractylodes lancea, panax ginseng, angelica acutiloba, bupleurum falcatum, zizyphus jujuba, citrus unshiu, glycyrrhiza uralensis, cimicifuga heracleifolia, zingiber officinale | 7.5 g/day | TID | 8 weeks | Standard care (no kampo) |
| Hamada et al. (2018) | Bojungikki-tang + pulmonary rehabilitation | Granules | Astragali radix (16.7%), atractylodis lanceae rhizome (16.7%), ginseng radix (16.7%), angelicae radix (12.5%), bupleuri radix (8.3%), zizyphi fructus (8.3%), aurantii nobilis pericarpium (8.3%), glycyrrhizae radix (6.3%), cimicifugae rhizome (4.2%), zingiberis rhizoma (2.0%) | 7.5 g/day | TID | 12 weeks | Pulmonary rehabilitation only |
| Hamada et al. (2022) | Bojungikki-tang + pulmonary rehabilitation | Granules | Astragali radix, atractylodis lanceae rhizoma, ginseng radix, angelicae radix, bupleuri radix, zizyphi fructus, aurantii nobilis pericarpium, glycyrrhizae radix, cimicifugae rhizoma, zingiberis rhizoma | 7.5 g/day | TID | 12 weeks | Pulmonary rehabilitation only |
| Hu et al. (2024) | Bojungikki-tang + conventional rehabilitation after laparoscopic surgery | Decoction | Angelica sinensis 15 g, dioscorea opposita 15 g, aurantii nobilis pericarpium 6 g, bupleurum chinense 6 g, glycyrrhiza uralensis 6 g, panax ginseng 9 g, cimicifuga heracleifolia 9 g, atractylodes macrocephala 9 g, amomi fructus 9 g, poria cocos 9 g, astragalus membranaceus 18 g | NR | BID | 14 days | Conventional rehabilitation surgery only |
| Huang (2015) | Modified bojungikki-tang + metformin + acarbose | Decoction | Base formula: Angelica sinensis 12 g, atractylodes macrocephala 15 g, lycium barbarum 15 g, panax ginseng 10 g, rehmannia glutinosa 15 g, poria cocos 15 g, astragalus membranaceus 30 g, bupleurum chinense 12 g, cimicifuga heracleifolia 6 g, citrus reticulata 10 g. | NR | BID | 8 weeks (2 cycles × 4 weeks) | Metformin + acarbose |
| Huang et al. (2025) | Bojungikki-tang | Granules | NR | NR | TID | 3 months | Not applicable |
| Kim et al. (2023) | Modified bojungikki-tang + acupuncture + pharmacopuncture | Decoction | Base formula (per dose): Ginseng radix 12 g, astragali radix 12 g, atractylodis rhizoma alba 4 g, angelicae radix 4 g, aurantii nobilis pericarpium 4 g, glycyrrhizae radix 4 g, perillae herba 2 g, agastachis herba 2 g, zingiberis rhizoma 4 g, ziziphi fructus 4 g. modifications: Initially added ephedrae herba 2 g, aconiti lateralis radix 2 g, asiasari radix 1 g, later removed, astragali radix +4 g added | NR | TID | 22 days (inpatient) | Not applicable |
| Kim et al. (2024) | Bojungikki-tang | Granules | Panax ginseng, atractylodes japonica, astragalus membranaceus, angelica gigas, zizyphus jujuba, bupleurum falcatum, citrus unshiu, glycyrrhiza uralensis, cimicifuga heracleifolia, zingiber officinale | 7.5 g/day | BID | 12 weeks + 24-week follow-up | Kyungok-go (KOG), cheonwangbosim-dan (CBD) |
| Kim and Keum (2015) | Modified bojungikki-tang | Powder | Astragalus membranaceus (astragali radix, 6 g), panax ginseng (ginseng radix, 4 g), glycyrrhiza uralensis (glycyrrhizae radix, 4 g), atractylodes macrocephala (atractylodis macrocephalae rhizoma, 4 g), fraxinus rhynchophylla (fraxini cortex, 2 g), angelica gigas (angelicae gigantis radix, 2 g), actaea/Cimicifuga spp. (cimicifugae rhizoma, 1.2 g), bupleurum falcatum (bupleuri radix, 1.2 g), plus massa medicata fermentata (amount NR), hordeum vulgare (hordei fructus germinatus, amount NR), crataegus pinnatifida (crataegi fructus, amount NR), proprietary “supp. A” (amount NR) | 6 g/day | TID | Mean 5.7 ± 2.7 months (range 3–11 months) | Not applicable |
| Kitahara et al. (2021) | Bojungikki-tang | Granules | Astragalus membranaceus (JP astragalus root), atractylodes japonica (JP atractylodes rhizome), panax ginseng (JP ginseng), angelica acutiloba (JP Japanese angelica root), bupleurum falcatum (JP bupleurum root), zizyphus jujuba (JP jujube), citrus unshiu (JP citrus unshiu peel), glycyrrhiza uralensis (JP glycyrrhiza), cimicifuga simplex (JP cimicifuga rhizome), zingiber officinale (JP processed ginger) | 7.5 g/day | TID | 3 months | Standard care only |
| Ko et al. (2025) | Bojungikki-tang + atezolizumab | Granules | Ginseng radix 1.33 g, atractylodis rhizoma alba 1.33 g, astragali radix 1.33 g, angelicae gigantis radix 1.0 g, zizyphi fructus 0.67 g, bupleuri radix 0.67 g, citri unshius pericarpium 0.67 g, cimicifugae rhizoma 0.33 g, zingiberis rhizoma recens 0.17 g, glycyrrhizae radix et rhizoma 0.5 g (daily dose) | 4 g/day | QD | 9 weeks (3 cycles) | Placebo + atezolizumab |
| Kohno et al. (2021) | Bojungikki-tang | Granules | Astragalus membranaceus (JP astragalus root), atractylodes lancea (JP atractylodes rhizome), panax ginseng (JP ginseng), angelica acutiloba (JP Japanese angelica root), bupleurum falcatum (JP bupleurum root), zizyphus jujuba (JP jujube), citrus unshiu (JP citrus unshiu peel), glycyrrhiza uralensis (JP glycyrrhiza), cimicifuga simplex (JP cimicifuga rhizome), zingiber officinale (JP ginger) | 7.5 g/day | TID | NR (administered until VRE-negative) | Probiotics ± standard care |
| Lee et al. (2025) | Bojungikki-tang | Granules | Panax ginseng 4.0 g, atractylodes japonica 4.0 g, astragalus membranaceus 4.0 g, angelica gigas 3.0 g, zizyphus jujuba 2.0 g, bupleurum falcatum 2.0 g, citrus unshiu 2.0 g, glycyrrhiza uralensis 1.5 g, cimicifuga heracleifolia 1.0 g, zingiber officinale 0.5 g (daily extract equivalent) | 7.5 g/day | BID | 8 weeks + 4-week follow-up | Waiting-list control (no active treatment) |
| Lee et al. (2021) | Gefitinib + modified bojungikki-tang | Decoction | Panax ginseng 24 g, astragalus membranaceus 24 g, liriope platyphylla 24 g, magnolia obovata 16 g, zingiber officinale 12 g, atractylodes japonica 8 g, angelica gigas 8 g, citrus reticulata 8 g, glycyrrhiza uralensis 8 g, pinellia ternata 8 g, ziziphus jujuba 8 g, cervus nippon 5 g, agastache rugosa 4 g, perilla frutescens 4 g | NR | TID | >78 months | Not applicable |
| Lee et al. (2015) | Bojungikki-tang | Granules | NR | 7.5 g/day | TID | 8 weeks | Not applicable |
| Lee et al. (2018) | Modified bojungikki-tang combined with salvia miltiorrhiza, ligusticum chuanxiong, angelica dahurica, and polygonum multiflorum thunb. | Powder | Astragali radix, atractylodis rhizoma, panacis ginseng radix, angelicae radix, bupleuri radix, zizyphi fructus, aurantii nobilis pericarpium, glycyrrhizae radix, cimicifugae rhizoma, zingiberis rhizoma, + salvia miltiorrhiza, ligusticum chuanxiong, angelica dahurica, polygonum multiflorum thunb. | 9 g/day | TID | 2 months | Not applicable |
| Lee (2017) | Bojungikki-tang + allergen-removed rhus verniciflua extract | Granules | Astragali radix 1.0 g, atractylodis rhizoma 1.0 g, ginseng radix 1.0 g, angelicae radix 0.75 g, bupleuri radix 0.5 g, zizyphi fructus 0.5 g, aurantii nobilis pericarpium 0.5 g, glycyrrhizae radix 0.375 g, cimicifugae rhizoma 0.25 g, zingiberis rhizoma 0.125 g | 3.75g/day | TID | 5 months | Not applicable |
| Lee et al. (2019) | Modified bojungikki-tang + Acupuncture | Decoction + Granules (hamsoapharm) | Ginseng radix 12 g, astragali radix 12 g, zingiberis rhizoma crudus 6 g, glycyrrhizae radix 4 g, atractylodis rhizoma alba 4 g, angelicae gigantis radix 4 g, citri pericarpium 4 g, jujubae fructus 4 g, amomi fructus 4 g, amomi rotundus fructus 4 g, alpiniae oxyphyllae fructus 4 g, agastachis herba 2 g, mori folium 2 g, bupleuri radix 0.14 g, cimicifugae rhizoma 0.08 g | NR | BID (decoction), TID (extract granule) | Decoction for 6 weeks), followed by extract granule for 2 weeks | Not applicable |
| Lee et al. (2024) | Bojungikki-tang | Granules | Atractylodis rhizoma alba 0.665 g, ginseng radix 0.665 g, astragali radix 0.665 g, angelicae gigantis radix 0.500 g, citri unshius pericarpium 0.335 g, bupleuri radix 0.335 g, zizyphi fructus 0.335 g, glycyrrhizae radix et rhizoma 0.250 g, cimicifugae rhizoma 0.165 g, zingiberis rhizoma 0.085 g | High-dose: 15 g/day; standard-dose: 7.5 g/day | TID | 4 weeks | Placebo |
| Li et al. (2021a) | Modified bojungikki-tang | Decoction | Radix astragalus membranaceus 60 g, radix panax ginseng 10 g, rhizoma atractylodes macrocephala 30 g, radix angelica sinensis 10 g, pericarpium citrus reticulata 5 g, radix polygalae tenuifolia 5 g, rhizoma cimicifuga heracleifolia 5 g, radix bupleurum chinense 5 g, fructus lycium barbarum 10 g, semen cuscuta chinensis 15 g, fructus schisandra chinensis 5 g, poria cocos with hostwood 10 g, rhizoma zingiber officinale 10 g, fructus ziziphus jujube 10 g, radix glycyrrhiza uralensis 5 g | NR | QD | 20 days (continued 6 months post-discharge) | Not applicable |
| Li et al. (2021b) | Bojungikki-tang | Decoction | NR | NR | NR | Mean: 1.3 years | Not applicable |
| Li et al. (2016) | Modified bojungikki-tang added to standard radio-/chemotherapy | Decoction | Astragalus membranaceus 60 g, hordeum vulgare germinated 25 g, Triticum aestivum germinated 25 g, atractylodes macrocephala 15 g, panax ginseng 15 g, citrus reticulata 10 g, bupleurum chinense 10 g, ligustrum lucidum 10 g, glycyrrhiza uralensis honey-fried 10 g, cimicifuga heracleifolia 10 g, eclipta prostrata 10 g, angelica sinensis 10 g, amomum villosum 6 g (+headache: Ligusticum chuanxiong & vitex trifolia 10 g, abdominal pain: Paeonia lactiflora 10 g, cough: Ophiopogon japonicus & schisandra chinensis 10 g) | NR | BID | From start of chemotherapy to 2 weeks post-chemotherapy (≈6 months total treatment course) | Standard radio-/chemotherapy only |
| Lu et al. (2021) | Modified bojungikki-tang + kangtai ointment (external) | Decoction | Paeonia lactiflora root 10 g, atractylodes macrocephala rhizome 10 g, angelica sinensis root 10 g, panax ginseng root 10 g, Bupleurum spp. root 9 g, actaea (cimicifuga) spp. rhizome 9 g, citrus reticulata pericarpium 6 g, glycyrrhiza uralensis (honey-fried) 5 g, astragalus membranaceus root 20 g | NR | BID | 14 days | Topical chitosan gel (once daily) |
| Minagawa et al. (2019) | Bojungikki-tang | Granules | Astragalus membranaceus, atractylodes japonica, panax ginseng, angelica acutiloba, bupleurum falcatum, zizyphus jujuba, citrus unshiu, glycyrrhiza uralensis, cimicifuga japonica, zingiber officinale | 7.5 g/day | TID | NR (follow-up until change in fatigue) | Not applicable |
| Ni et al. (2021) | Bojungikki-tang | Decoction | Astragalus membranaceus 30 g, poria cocos 15 g, codonopsis pilosula 15 g, atractylodes macrocephala 12 g, cimicifuga heracleifolia 9 g, bupleurum chinense 6 g, citrus reticulata 9 g, angelica sinensis 15 g, acorus tatarinowii 15 g, salvia miltiorrhiza 15 g, epimedium brevicornum 18 g, rehmannia glutinosa (prepared) 18 g | NR | BID | 3 months | Not applicable |
| Oh et al. (2023) | Bojungikki-tang + glucose-lowering drugs | Granules | Bigwa BIT: Astragalus membranaceus 2.84 g, atractylodes macrocephala 1.90 g, gardenia jasminoides 1.90 g, angelica gigas 1.90 g, glycyrrhiza uralensis 1.90 g, citrus reticulata 1.90 g, liriope platyphylla 1.90 g, magnolia biondii 1.90 g, panax ginseng 1.90 g, cimicifuga heracleifolia 0.95 g, asarum sieboldii 0.95 g, bupleurum falcatum 0.95 g Hanshin BIT: Atractylodes macrocephala 1.25 g, panax ginseng 1.25 g, glycyrrhiza uralensis 1.25 g, astragalus membranaceus 1.88 g, angelica gigas 0.63 g, citrus reticulata 0.63 g, cimicifuga heracleifolia 0.63 g, bupleurum falcatum 0.38 g Kracie BIT: Atractylodes macrocephala 2.0 g, panax ginseng 2.0 g, glycyrrhiza uralensis 0.75 g, astragalus membranaceus 2.0 g, angelica gigas 1.5 g, citrus reticulata 1.0 g, cimicifuga heracleifolia 0.5 g, bupleurum falcatum 1.0 g, zingiber officinale 0.25 g, ziziphus jujuba 1.0 g |
7.5-10 g/day | BID or TID | 1–324 days (mean: 30.9 days) | Not applicable |
| Okabe et al. (2019) | Bojungikki-tang + S-1 adjuvant chemotherapy | Granules | 10-Herb formula: Astragalus membranaceus, atractylodes macrocephala, panax ginseng, angelica acutiloba, bupleurum chinense, ziziphus jujuba, citrus unshiu, glycyrrhiza uralensis, cimicifuga heracleifolia, zingiber officinale (dosage not reported) | 7.5 g/day | QD | 1 year | S-1 alone |
| Okugawa et al. (2024) | Bojungikki-tang | Granules | Astragalus membranaceus 4.0 g, atractylodes lancea 4.0 g, panax ginseng 4.0 g, angelica acutiloba 3.0 g, bupleurum chinense 2.0 g, ziziphus jujuba 2.0 g, citrus unshiu 2.0 g, glycyrrhiza uralensis 1.5 g, cimicifuga heracleifolia 1.0 g, zingiber officinale 0.5 g | 7.5 g/day | TID | ≥3 months | Not applicable |
| Park et al. (2025) | Modified bojungikki-tang | Decoction | Astragalus membranaceus 4 g, angelica gigas 4 g, Cervus elaphus (cervi cornus colla) 1.67 g, panax ginseng 1.33 g, atractylodes macrocephala 1.33 g, glycyrrhiza uralensis 1.33 g, Equus asinus (asini corii colla) 1.33 g, rehmannia glutinosa 1.33 g, cimicifuga heracleifolia 0.67 g, bupleurum falcatum 0.67 g, citrus unshiu 0.67 g, poria cocos 0.67 g, alisma orientale 0.67 g, zingiber officinale 0.27 g | NR | TID (first 24 weeks), then BID | 12 months +12-month follow-up | Not applicable |
| Qian et al. (2024) | Bojungikki-tang | Pills | Astragalus membranaceus, codonopsis pilosula, atractylodes macrocephala, angelica sinensis, cimicifuga foetida, bupleurum chinense, citrus reticulata (pericarpium citri reticulatae), glycyrrhiza uralensis | 30 pills/day | TID | 6 chemotherapy cycles with 7-day washout after 3 cycles | Placebo |
| Qiu et al. (2024) | Modified bojungikki-tang | Decoction | Astragalus membranaceus 80 g, angelica sinensis (stir-fried) 12 g, atractylodes macrocephala (stir-fried) 30 g, codonopsis pilosula 30 g, citrus reticulata 6 g, glycyrrhiza uralensis 9 g, panax ginseng 15 g, cimicifuga foetida 9 g, bupleurum chinense 6 g, dioscorea opposita (stir-fried) 6 g, epimedium brevicornum 30 g, coix lacryma-jobi (stir-fried) 30 g, lablab purpureus (stir-fried) 15 g, euryale ferox (stir-fried) 15 g, bombyx batryticatus 9 g, scolopendra subspinipes 2 g | NR | Initially BID → then QD | 30 months | Not applicable |
| Seo et al. (2019) | Bojungikki-tang | Decoction | Astragali radix 12 g, ginseng radix 12 g, atractylodis rhizoma alba 12 g, glycyrrhizae radix 12 g, angelicae gigantis radix 8 g, aurantii nobilis pericarpium 4 g, cimicifugae rhizoma 4 g, bupleuri radix 4 g | 150 mL/day | TID | 10 days | Not applicable |
| Takeuchi et al. (2017) | Bojungikki-tang | Granules | NR | 7.5 g/day | NR | NR | Not applicable |
| Teng et al. (2016) | Modified bojungikki-tang + norethindrone | Decoction | Astragalus membranaceus 40 g, atractylodes macrocephala (bran-fried) 15 g, citrus reticulata 10 g, cimicifuga foetida 15 g, bupleurum chinense 10 g, codonopsis pilosula 20 g, glycyrrhiza uralensis (honey-fried) 10 g, pueraria lobata 20 g, dipsacus asper 15 g | NR | BID | 3 months | Norethindrone tablets |
| Terai et al. (2020) | Bojungikki-tang | Granules | NR | 7.5 g/day | TID | 12 weeks | Antioxidant supplement |
| Tokumasu et al. (2025) | Bojungikki-tang | Granules | JUNKOU formulation: Ginseng 4.0 g, jujube 2.0 g, atractylodis rhizoma 4.0 g, bupleuri radix 2.0 g, astragali radix 4.0 g, glycyrrhizae radix 1.5 g, angelicae gigantis radix 3.0 g, zingiberis rhizoma 0.5 g, aurantii nobilis pericarpium 2.0 g, cimicifugae rhizoma 1.0 g. TSUMURA formulation: Astragali radix 4.0 g, atractylodis lanceae rhizoma 4.0 g, ginseng radix 4.0 g, angelicae gigantis radix 3.0 g, bupleuri radix 2.0 g, jujubae fructus 2.0 g, aurantii nobilis pericarpium 2.0 g, glycyrrhizae radix 1.5 g, cimicifugae rhizoma 1.0 g | 7.5 g/day | BID or TID | 8 weeks | Not applicable |
| Wang (2016) | Modified bojungikki-tang | Decoction | Codonopsis pilosula 24 g; astragalus membranaceus 24 g; atractylodes macrocephala (fried) 24 g; angelica sinensis 12 g; citrus reticulata pericarp 12 g; bupleurum chinense 6 g; Cimicifuga spp. 6 g; glycyrrhiza uralensis (honey-fried) 9 g | 400 mL | BID | 1 month | Domperidone (oral), TID, 1 month |
| Wang et al. (2021) | Bojungikki-tang + THP bladder perfusion | Decoction | Astragalus membranaceus (root) 25 g, panax ginseng (root) 10 g, angelica gigas (root) 10 g, glycyrrhiza uralensis (root) 6 g, atractylodes macrocephala (rhizome) 10 g, cimicifuga foetida (rhizome) 10 g, citrus reticulata (pericarp) 10 g, bupleurum chinense (root) 10 g | NR | BID | 12 months | THP (pirarubicin) bladder perfusion alone |
| Watanabe and Maeda (2022) | Bojungikki-tang | Granules | Astragalus membranaceus 2.5 g, atractylodes lancea 2.5 g, panax ginseng 2.5 g, angelica acutiloba 1.88 g, bupleurum falcatum 1.25 g, zizyphus jujuba 1.25 g, citrus unshiu peel 1.25 g, glycyrrhiza uralensis 0.94 g, cimicifuga simplex 0.63 g, zingiber officinale 0.30 g (per 7.5 g extract) | 7.5 g/day | TID | From postoperative day 3 until discharge (∼6–10 weeks) | Usual postoperative rehabilitation only (no BIT) |
| Wu et al. (2017) | Bojungikki-tang | Granules | Astragalus membranaceus 15 g, codonopsis pilosula 15 g, atractylodes macrocephala 10 g, angelica sinensis 6 g, citrus tangerina peel 6 g, bupleurum chinense 5 g, cimicifuga foetida 5 g, glycyrrhiza uralensis (prepared) 5 g | 200 mL/day | BID | 2 weeks | Positive control: No BIT (food allergy only); Negative control: No food allergy, no BIT |
| Xu et al. (2023) | Bojungikki-tang + conventional western medicine | Decoction | Astragali radix, ginseng radix, glycyrrhizae radix, atractylodis macrocephalae rhizoma, angelicae sinensis radix, citri reticulatae pericarpium, cimicifugae rhizoma, bupleuri radix | 200 mL/day | QD | 28 days | Conventional western medicine |
| Yang (2016) | Mosapride + bojungikki-tang | Pills | NR | 9 g/day | TID | 30 days | Mosapride alone |
| Zhang and Zhu (2015) | Modified bojungikki-tang + topical powder (Xueping capsule content) | Decoction | Astragalus membranaceus 50 g, codonopsis pilosula 20 g, atractylodes macrocephala 15 g, glycyrrhiza uralensis 6 g, angelica sinensis 8 g, citrus reticulata 12 g, poria cocos 15 g, bupleurum chinense 6 g, cimicifuga foetida 6 g, sanguisorba officinalis 12 g, rubia cordifolia 12 g | 400 mL/day | BID | 7 days | Metronidazole topical powder only |
| Zhou et al. (2022) | Modified bojungikki-tang | Decoction | Astragalus membranaceus 15 g, atractylodes macrocephala (fried) 15 g, citrus reticulata 6 g, cimicifuga foetida 6 g, bupleurum chinense 9 g, ginseng radix 15 g, glycyrrhiza uralensis 3 g, angelica sinensis 12 g, alpinia oxyphylla 15 g, mantidis ootheca 9 g, eucommia ulmoides 15 g, lindera aggregata 6 g, rosa laevigata michx 15 g (modifications allowed) | NR | BID | 4 weeks | Not applicable |
BID, twice daily; BIT, Bojungikki-tang; NR, not reported; QD, once daily; TID, three times daily.
3.3.2. Treatment duration and exposure patterns
Treatment duration varied substantially across studies, ranging from short-term courses of 1 week to extended interventions lasting up to 30 months. Most clinical trials implemented treatment periods between 4 and 12 weeks, reflecting a common timeframe for evaluating functional and symptomatic outcomes. Several studies reported long treatment or observation periods of 6 months or more, but explicit follow-up beyond the active treatment period was reported in only 3 studies (6.4%), limiting assessment of whether functional or symptomatic improvements were sustained after discontinuation of BIT (Table 2).
3.3.3. Composition of Bojungikki-tang and modified formulations
Across the included studies, a consistent core composition corresponding to the classical ten-botanical drug BIT preparation was repeatedly employed, particularly in standardized granule-based preparations. This canonical structure, typically consisting of Astragali Radix, Ginseng Radix, Atractylodis Rhizoma, Angelicae Radix, Bupleuri Radix, Zizyphi Fructus, Aurantii Nobilis Pericarpium, Glycyrrhizae Radix, Cimicifugae Rhizoma, and Zingiberis Rhizoma, was used with minimal or no variation in multiple studies, largely those using commercial formulations in South Korea and Japan (Akita et al., 2019; Edahiro et al., 2022; Hamada et al., 2018; Hamada et al., 2022; Kitahara et al., 2021; Kohno et al., 2021; Minagawa et al., 2019; Okabe et al., 2019; Okugawa et al., 2024; Watanabe and Maeda, 2022; Kim et al., 2024; Ko et al., 2025; Lee et al., 2025; Lee, 2017; Tokumasu et al., 2025). Beyond this standardized formulation, the majority of studies implemented modified versions that preserved the core botanical drugs while incorporating additional botanical drugs to address disease-specific pathophysiology. Frequently added botanical drugs included Codonopsis Radix and Leonuri Herba (Chen et al., 2024; Chen et al., 2018; Ni et al., 2021; Wang, 2016; Wu et al., 2017; Zhang and Zhu, 2015), Salviae Radix and Ligustici Rhizoma (Chen et al., 2024; Chen et al., 2018; Lee et al., 2018; Li et al., 2016; Ni et al., 2021), Dipsaci Radix and other gynecologic-supporting botanical drugs (Chen et al., 2024; Chen et al., 2018; Teng et al., 2016), Rehmanniae Radix and Poria cocos (Hu et al., 2024; Huang, 2015; Ni et al., 2021; Park et al., 2025; Zhang and Zhu, 2015), Epimedii Herba and Dioscoreae Rhizoma (Hu et al., 2024; Ni et al., 2021; Qiu et al., 2024), and various digestive-supporting botanical drugs such as Amomi Fructus and related adjuncts (Chen et al., 2024; Hu et al., 2024; Kim and Keum, 2015; Lee et al., 2019; Li et al., 2016). The extent of modification varied considerably, ranging from minor additions to complex prescriptions containing more than fifteen medicinal materials (Li et al., 2021a; Ni et al., 2021; Qiu et al., 2024). Several studies explicitly allowed flexible adjustment of botanical drugs based on patient presentation, reflecting individualized traditional prescribing practices (Kim et al., 2023; Li et al., 2016; Zhou et al., 2022). In contrast, a subset of studies did not report detailed compositional information (Huang et al., 2025; Lee et al., 2015; Li et al., 2021b; Takeuchi et al., 2017; Terai et al., 2020; Yang, 2016), limiting precise assessment of formulation structure and dosage characteristics in those cases (Table 2).
3.4. Outcome domains and reporting patterns
Across the included studies, outcome selection was diverse and reflected the wide range of clinical contexts in which BIT was evaluated. Symptom-focused patient-reported measures and condition-specific clinical scores were used most often, including pain and neuropathic symptom instruments (Kim et al., 2023; Kim and Keum, 2015), pelvic and urinary symptom measures for postpartum or female urinary conditions (Chen et al., 2024; Chen et al., 2018; Zhou et al., 2022), and urinary retention–related monitoring in post-stroke care (Seo et al., 2019). Several studies also applied syndrome- or symptom-based scoring approaches alongside functional indices, particularly in integrative medicine settings (Hu et al., 2024; Li et al., 2016). Symptom trajectory and supportive care outcomes were also reported, including fatigue-related measures (Minagawa et al., 2019), general weakness and hair regrowth with laboratory monitoring (Lee, 2017), and autonomic or sleep-related symptom scoring with appetite/weight tracking (Lee et al., 2019).
Quality-of-life (QOL) outcomes were commonly assessed using generic and disease-specific tools, such as EORTC QLQ-C30, SF-36, EQ-5D/EQ-VAS, dermatology-related measures, and rhinitis-specific QOL instruments (Edahiro et al., 2022; Hamada et al., 2018; Hu et al., 2024; Kim et al., 2023; Kim et al., 2024; Lee et al., 2025; Lee et al., 2015; Lee et al., 2018; Lee et al., 2024; Li et al., 2016; Park et al., 2025; Qian et al., 2024; Watanabe and Maeda, 2022). Functional performance and activity endpoints were also frequently reported, particularly in respiratory and postoperative populations, including 6-min walking distance, step counts, dyspnea indices, physical activity metrics, and rehabilitation-related milestones (Hamada et al., 2018; Hamada et al., 2022; Watanabe and Maeda, 2022). Disease-specific functional scales were additionally used in neuromuscular and neurologic conditions, including strength-based assessments and validated disease scores (Kitahara et al., 2021; Li et al., 2021a; Li et al., 2021b; Qiu et al., 2024).
Laboratory and biomarker outcomes were incorporated across indications and included inflammatory markers (e.g., CRP and cytokines), nutritional indices (e.g., albumin and related measures), immune-related profiles (cell subsets and immunoglobulins), and metabolic or endocrine parameters (Akita et al., 2019; Hu et al., 2024; Huang, 2015; Ko et al., 2025; Lee et al., 2025; Li et al., 2016; Oh et al., 2023; Okugawa et al., 2024; Takeuchi et al., 2017; Terai et al., 2020). Infection-related studies also used microbiologic and clinical endpoints such as colonization status, febrile infectious events, and pneumonia severity or pathogen eradication indices (Kitahara et al., 2021; Kohno et al., 2021, Xu et al., 2023). Microbiome-related endpoints were reported in several studies, including gut microbiota composition and fecal metabolomic profiling, as well as wound-flora characterization in postoperative settings (Huang et al., 2025; Lee et al., 2025; Ni et al., 2021; Wu et al., 2017). In oncology-focused studies, outcomes extended beyond symptom and QOL measures to include performance status, tumor markers, and treatment response or survival-related endpoints (Hu et al., 2024; Ko et al., 2025; Lee et al., 2021; Okabe et al., 2019; Okugawa et al., 2024; Qian et al., 2024; Wang et al., 2021). Postoperative and wound-healing studies more often prioritized recovery-oriented endpoints such as time to wound healing, duration of discharge or bleeding, and pain resolution (Akita et al., 2019; Lu et al., 2021; Wu et al., 2017; Zhang and Zhu, 2015). Several gastrointestinal and gynecologic studies reported pragmatic effectiveness outcomes, including total effective rate and recurrence during follow-up (Teng et al., 2016; Wang, 2016; Yang, 2016). Overall, outcomes clustered around symptom burden, functional recovery, and QOL, but the breadth of instruments and reporting approaches limited direct comparability across studies, even within the same disease system (Table 3).
TABLE 3.
Outcome measures, main findings, and safety reporting of included studies.
| Study ID | Outcome measures | Main findings | Safety (AE) |
|---|---|---|---|
| Akita et al. (2019) | 1. DESIGN-R score; 2. Albumin; 3. CRP; 4. IL-6 | 1.100% (8/8) vs. 33.3%; 2.4.0 g/dL vs. 3.6 g/dL; 3.0.7 mg/dL vs. 5.0 mg/dL; 4.6.8 pg/mL vs. 12.2 pg/mL | NR |
| Chen et al. (2024) | 1. ICIQ-SF score; 2. Pelvic floor muscle strength; 3. Vaginal systolic pressure (VSP), resting pressure (VRP), duration; 4. Urodynamic parameters (ALPP, MUCP, Qmax, BC); 5. Total effective rate; 6. I-QOL score | 1. ICIQ-SF: TG significantly lower vs. CG (p < 0.05); 2. Pelvic floor muscle strength: TG significantly higher vs. CG (p < 0.05); 3. VSP/VRP/duration: all significantly improved in TG vs. CG (p < 0.05); 4. Urodynamics (ALPP, MUCP, Qmax, BC): TG significantly improved vs. CG (p < 0.05); 5. Total effective rate: TG 125/128 (97.66%) vs. CG 100/128 (78.12%) (p < 0.001); 6. I-QOL: TG significantly higher vs. CG (p < 0.05) | NR |
| Chen et al. (2018) | 1. Pelvic floor muscle strength: EMG (μV), duration (s), vaginal pressure (cmH2O), EMG score; 2. Urinary incontinence improvement rate; 3. Sexual life quality improvement rate; 4. TGF-β1; 5. MMP-2; 6. TIMP-2 | 1. Pelvic floor muscle strength outcomes were significantly improved in TG (all p < 0.05); 2. Urinary incontinence improvement rate was higher in TG (p < 0.05); 3. Sexual life quality improvement rate was higher in TG (p < 0.05); 4. TGF-β1 was significantly higher in TG (p < 0.05); 5. MMP-2 was significantly lower in TG (p < 0.05); 6. TIMP-2 was significantly higher in TG (p < 0.05) | NR |
| Edahiro et al. (2022) | 1. MPN-SAF TSS; 2. ≥50% improvement in MPN-SAF TSS; 3. ≥20% improvement in MPN-SAF TSS; 4. EORTC QLQ-C30 (global health status/QOL, MID ≥10-point improvement) | 1. MPN-SAF TSS: TG 23→17→18 vs. CG 22→∼22→∼22 (p = 0.299; no significant difference); 2. ≥50% improvement: TG 19% (4w), 20% (8w) vs. CG 16% (4w), 21% (8w); 3. ≥20% improvement: TG 57% (4w), 55% (8w) vs. CG 26% (4w), 26% (8w); 4. QOL MID ≥10-point improvement: TG 52.9% (4w) vs. CG 33.3% (4w). TG 26.7% (8w) vs. CG 40% (8w) | Grade 1 liver dysfunction (1/21, 4.8%), resolved after stopping |
| Hamada et al. (2018) | 1. 6MWD; 2. Body weight; 3. %IBW; 4. mMRC dyspnea; 5. VAS-dyspnea; 6. VAS-fatigue; 7. CAT total | 1. No significant between-group difference was observed in 6MWD; 2. Body weight increased in TG (p < 0.05); 3. %IBW increased in TG (p < 0.05); 4. mMRC dyspnea improved in TG (p < 0.05); 5. VAS-dyspnea improved in TG (p < 0.05); 6. VAS-fatigue improved in TG (p < 0.05); 7. CAT total improved in TG (p < 0.005) | No AE related to TJ-41; 1 death (abdominal aneurysm, unrelated); 1 pneumonia (CG); 2 COPD exacerbations (CG) |
| Hamada et al. (2022) | 1. Apathy scale (AS); 2. Total number of steps; 3. PHQ-9; 4. VAS (dyspnea); 5. CAT (energy) | 1. Apathy scale improved in TG compared with CG (p = 0.049); 2. Total number of steps was significantly higher in TG (p = 0.013); 3. PHQ-9 improved in TG (p = 0.031); 4. VAS-dyspnea improved in TG (p = 0.021); 5. CAT-energy improved in TG (p = 0.026) | 1 mild liver dysfunction, 1 lumbar spinal canal stenosis; causal relation to TJ-41 unknown |
| Hu et al. (2024) | 1. TCM syndrome scores (abdominal bloating, fatigue, emaciation, loose stool, loss of appetite, vomiting); 2. KPS score; 3. Immune function (CD3+, CD4+, CD8+, CD4+/CD8+, NK cells, IgG, IgA, IgM); 4. Inflammatory mediators (IL-10, IL-6, TNF-α, CRP); 5. Tumor markers (CEA, CA19-9, VEGF, TSGF); 6. SF-36 QOL | 1. TCM syndrome scores were significantly improved compared with control (all p < 0.001); 2. KPS was significantly higher in the treatment group (p < 0.001); 3. Immune function indices were significantly improved (all p < 0.001); 4. Inflammatory mediators were significantly improved (all p < 0.001); 5. Tumor markers were significantly lower in the treatment group (all p < 0.001); 6. SF-36 QOL was significantly improved (p < 0.001) | TG: 6/50 (12.0%) – nausea (1), bloating (1), infection (2), fistula (1), gastric retention (1); CG: 15/50 (30.0%) – nausea (3), vomiting (3), abdominal pain (4), infection (3), fever (2) |
| Huang (2015) | 1. FPG, 2hPG, HbA1c; 2. Glycemic control rate | 1. FPG: 6.5 ± 1.5 vs. 7.5 ± 1.2 mmol/L 2hPG: 8.5 ± 2.2 vs. 10.2 ± 2.0 mmol/L. HbA1c: 6.9% ± 1.4% vs. 7.7% ± 1.3%; 2. Glycemic control rate: 93.7% (59/63) vs. 81.0% (51/63) | NR |
| Huang et al. (2025) | 1. Apnea–Hypopnea index (AHI); 2. Micro-arousal index; 3. Minimum oxygen saturation (%); 4. Average oxygen saturation (%); 5. Gut microbiota abundance (alistipes, AR/PCNA pathway) | 1. AHI: 61.2 ± 23.6 → 40.3 ± 19.2 (p = 0.0338); 2. Micro-arousal index: 56.6 ± 21.3 → 36.7 ± 21.1 (p = 0.0396); 3. Minimum SpO2: 66.3 ± 11.8 → 83.9 ± 4.4 (p = 0.0002); 4. Average SpO2: 88.9 ± 5.1 → 94.6 ± 2.0 (p = 0.0025); 5. Gut microbiota: ↑ Alistipes, activation of AR and PCNA gene pathways, improved flora balance (p < 0.05) | NR |
| Kim et al. (2023) | 1. NRS; 2. SF-MPQ; 3. EQ-5D; 4. LANSS | 1. NRS: 7 → 4; 2. SF-MPQ (sensory): 29 → 10; 3. SF-MPQ (affective): 8 → 1; 4. EQ-5D: 0.356 → 0.751 | NR |
| Kim et al. (2024) | 1. VAS (fatigue, cognitive dysfunction); 2. CIS; 3. ChFS (total, physical, mental); 4. K-MoCA; 5. CFQ; 6. EQ-5d-5l; 7. PSQI-K; 8. BDI | 1. Fatigue VAS improved within groups, with the highest success rate in the BIT group; 2. No significant between-group difference was observed for cognitive dysfunction VAS; 3. CIS improved significantly in all groups; 4. ChFS showed numerical improvement, without significant between-group difference; 5. K-MoCA improved only in the KOG group (p < 0.05); 6. CFQ improved during follow-up in all groups; 7. PSQI-K improved in the KOG group (p < 0.05); 8. BDI improved in the BIT and KOG groups (p < 0.05) | TG: BIT (33.3%), KOG (6.7%), CBD (26.7%); all mild, none drug-related |
| Kim and Keum (2015) | NIH-CPSI (total, pain, urinary, quality-of-life) | NIH-CPSI total: 37.6 ± 5.8 → 7.5 ± 3.9 (p < 0.001); pain: 17.5 ± 3.9 → 3.1 ± 2.3 (p < 0.001); urinary: 9.2 ± 1.0 → 1.5 ± 0.9 (p < 0.001); QoL: 10.9 ± 1.4 → 2.8 ± 1.3 (p < 0.001) | NR |
| Kitahara et al. (2021) | 1. MRSA colonization; 2. Febrile infectious diseases; 3. Modified rankin scale (mRS) | 1. MRSA colonization: 7.3% (3/41) vs. 25.0% (8/32) (p = 0.0497); 2. Febrile infectious diseases: 17.1% (7/41) vs. 46.9% (15/32) (p = 0.0096); 3. mRS: 4.66 ± 0.88 vs. 5.06 ± 0.44 (p = 0.0329) | NR |
| Ko et al. (2025) | 1. AE & irAE incidence; 2. Fatigue (EORTC-QLQ-c30, FACIT-F, NRS); 3. Muscle loss (SARC-F, body comp., sit-to-stand); 4. Immune markers (PBMC profiling) 5. ORR & DCR | 1. AE: 64.29% (9/14) vs. 42.86% (6/14) (p = 0.2556). irAE: 7.14% (1/14) vs. 0% (0/14); 2. Fatigue: improvement trend, Q10 at visit 5 favored BIT (p = 0.0498); 3. SARC-F trend improved vs. placebo (NS); 4. ↓ PD-1+CD8+ T cells (p = 0.0492), ↑ NK cells (p = 0.0191); 5. ORR: 16.67% vs. 8.33%; DCR: 41.67% vs. 25.0% (NS) | TG 9/14 (64.29%) vs. CG 6/14 (42.86%); Grade≥3 irAE only in TG: 1 pt (7.14%) with pneumonia; most AEs mild–moderate |
| Kohno et al. (2021) | 1. Rate of VRE negative conversion; 2. Time to negative conversion; 3. Overall survival; 4. Mortality rate | 1. VRE negative conversion: 28.2% (11/39) vs. 6.0% (5/83), (p = 0.0014); 2. Shorter time to negative conversion in NG-tube subgroup (p = 0.0485); 3. Improved overall survival with kampo treatment (p = 0.031); 4. Mortality reduced when VRE negative conversion achieved (p = 0.0003) | 1 case of hypokalemia (improved with spironolactone) |
| Lee et al. (2025) | 1. Anorexia VAS; 2. SCORAD; 3. DLQI; 4. Topical steroid use; 5. Cytokines (IL-1β, IL-4, IL-17); 6. Gut microbiome changes | 1. VAS ↓: week 8 TG 32.33 vs. CG 52.19 (p = 0.0347); 2. SCORAD ↓ only in TG: −11.59 at week 8 (p = 0.0078); 3. DLQI ↓ only in TG at week 8 (p = 0.0113); 4. Topical steroid use lower in TG at week 4 (p = 0.0308); 5. IL-1β ↓ only in TG (p = 0.0057), IL-4 & IL-17 ↓ both groups, more in TG; 6. Microbiome: ↓ gemella. ↑ gemmiger formicilis | TG 10 cases vs. CG 5 cases (NS, p = 0.7602); no serious AEs; 1 fasting glucose elevation in TG judged unrelated |
| Lee et al. (2021) | 1. Progression-free survival (PFS); 2. Tumor response (RECIST); 3. Brain metastasis response; 4. Skin toxicity | 1. PFS maintained for >78 months; 2. Tumor size reduced from 3.9 cm → 1.5 cm (61.5% reduction); 3. Brain metastasis: complete disappearance; 4. Skin toxicity: Grade 1→3 rash from gefitinib, improved after dose reduction | No AE associated with BIT reported |
| Lee et al. (2015) | 1. Fatigue (FSS); 2. Quality of life (EORTC QLQ-C30); 3. Blood chemistry & hematology | 1. FSS: 36 → 19 after treatment; 2. QOL (global): 50 → 83.3 after treatment; 3. Blood tests: No significant change | NR |
| Lee et al. (2018) | 1. CCMQ (constitution type); 2. SF-36 (quality of life); 3. Flu-like symptom frequency and severity | 1. CCMQ: Qi deficiency, blood stasis, and allergy patterns decreased markedly after 2 months; 2. SF-36: general health improved from 10 → 65 (+50%); 3. Flu-like symptoms (fever, dizziness, headache) markedly reduced. Fever subsided, improved appetite and energy | NR |
| Lee (2017) | 1. General weakness; 2. Hair loss recovery; 3. Laboratory findings (CBC, LFT) | 1. General weakness improved after 3 months; 2. New hair growth observed after 3 months, black regrowth at 5 months despite ongoing chemotherapy; 3. Hb decreased from 12.9 → 8.0 g/dL, WBC 7880 → 3,470/μL, platelets 320 K → 172 K, indicating no hematologic recovery | NR |
| Lee et al. (2019) | 1. Global assessment scale (GAS) for sweating; 2. GAS for palpitation; 3. Sleep quality; 4. Appetite/weight; 5. Bowel movement | 1. GAS for sweating: 100 → 0 after 6 weeks, slight relapse to 20 at week 15; 2. GAS for palpitation: 100 → 0 after 6 weeks; 3. Sleep improved (sleeping time ↑ from 2 to 3 h → 6–7 h); 4. Weight ↑ by 1.5–2 kg; 5. Constipation resolved | NR |
| Lee et al. (2024) | 1. TNSS (r-TNSS & i-TNSS); 2. KARQLQ; 3. Total IgE; 4. Eosinophil count; 5. Overall assessment | 1. r-TNSS: High 4.52 ± 1.99 vs. standard 3.97 ± 1.84 vs. Placebo 4.47 ± 1.90 (NS). i-TNSS: High 4.29 ± 2.03 vs. standard 3.53 ± 1.75 vs. Placebo 4.06 ± 1.85 (NS); 2. KARQLQ: All improved. No significant group difference; 3–4. IgE & eosinophils: No significant group differences; 5. Overall assessment: High 2.09 ± 0.84 vs. standard 2.21 ± 0.65 vs. Placebo 2.21 ± 0.59 (NS) | High-dose 11.4% (4/35), standard-dose 11.4% (4/35), Placebo 5.7% (2/35); all mild, none serious |
| Li et al. (2021a) | 1. FSHD evaluation scale; 2. Muscle strength; 3. Weight | 1. FSHD score improved from 9 → 6; 2. Muscle strength from 3 to 4/5 → 4–5/5; 3. Weight increased +2.5 kg | NR |
| Li et al. (2021b) | 1. JOMG clinical score (0–1); 2. Anti-AChR antibody (nmol/L) | 1. JOMG score improved from 0.9 to 0.2 (overall); 2. AChR-ab decreased from 2.33 to 1.21 nmol/L (overall) 3) each 1 nmol/L ↑ in AChR-ab increased odds of symptom presence by 40% (OR: 1.40) 4) each treatment-time interval ↓ odds of symptoms by 53% (OR: 0.47) | NR |
| Li et al. (2016) | 1. T-cell subsets (CD4, CD8, CD4/CD8); 2. TCM symptom score; 3. Quality of life (EORTC QLQ-C30 domains: function, symptom, global health); 4. AEs | 1. CD4 (%) 39.42 ± 5.21 vs. 35.21 ± 9.84. CD8 24.84 ± 5.21 vs. 28.07 ± 7.65. CD4/CD8 1.59 ± 0.23 vs. 1.26 ± 0.28 (P < 0.05); 2. TCM symptom score 5.36 ± 4.98 vs. 12.48 ± 5.21 (P < 0.001); 3. Functional QoL 29.54 ± 3.25 vs. 21.12 ± 2.94. Symptom QoL 30.32 ± 2.97 vs. 19.96 ± 2.25. Global health 28.87 ± 3.64 vs. 20.23 ± 2.45 (all P < 0.001); 4. AE 15% (6/40) vs. 40% (16/40) (P = 0.012) | Leukopenia: 10.0% vs. 20.0%; Hemoglobin↓: 7.5% vs. 15.0%; Platelet↓: 10.0% vs. 17.5%; GI adverse reactions: 15.0% vs. 40.0% (p = 0.012); bone marrow suppression: 17.5% vs. 35.0% |
| Lu et al. (2021) | 1. Total effective rate (Primary); 2. Quality-of-life score; 3. Time to wound healing; 4. Time to pain resolution; 5. Pain index (VAS); 6. Perianal edema score; 7. Anal manometry (anal canal length. Resting pressure. max diastolic. max systolic); 8. Wound exudate score (7 & 14 days) | 1. Total effective rate was higher in TG than in CG (p = 0.004); 2. Quality-of-life score was significantly higher in TG (p < 0.001); 3. Time to wound healing was shorter in TG (p < 0.001); 4. Time to pain resolution was shorter in TG (p < 0.001); 5. Pain index was significantly lower in TG (p < 0.001); 6. Perianal edema score was significantly lower in TG (p < 0.001); 7. Anal manometry outcomes were significantly improved in TG (all p ≤ 0.002); 8. Wound exudate score was significantly lower in TG (p < 0.001) | TG 3.3% (2/60) vs. CG 16.7% (10/60), p = 0.013; types included fever, wound exudate, bleeding, perianal edema |
| Minagawa et al. (2019) | 1. Cancer fatigue scale (CFS) score (total & subdomains); 2. Enzalutamide treatment continuation after HET initiation | 1. CFS: Improved in 2/3 cases (CFS score decreased). Worsened in 1/3 cases; 2. Enzalutamide continuation duration: 193.0 days (hochuekkito cases) vs. 173.2 days (general fatigue w/o hochuekkito) vs. 265.6 days (no fatigue) | NR |
| Ni et al. (2021) | 1. Sex hormones (testosterone, DHEAS); 2. Ovulation rate; 3. Quality-of-life score; 4. BMI, WHR; 5. LH, FSH, PRL; 6. FBG, FINS, HOMA-IR; 7. Cycle length; 8. Follicle count; 9. Gut microbiota (16S rRNA); 10. Fecal metabolites (metabolomics) | 1. Testosterone ↓ (p < 0.001), DHEAS ↓ (p < 0.001); 2. Ovulation ↑ from 33% → 78%; 3. QoL ↑ significantly; 4. BMI ↓, WHR ↓ (p NR); 5. LH ↓ (p < 0.001), FSH ↑ (p < 0.05), PRL ↓ (p < 0.05); 6. FBG ↓ (p < 0.05), FINS ↓ (p < 0.05), HOMA-IR ↓ (NS); 7. Cycle length ↓ (p < 0.001); 8. Follicle count ↓ (p < 0.001); 9. ↑ [Eubacterium]_rectale_group, Escherichia–Shigella, fusicatenibacter (p < 0.05), ↓ megamonas (p < 0.05); 10.106 metabolites changed, 14 KEGG pathways significantly enriched | NR |
| Oh et al. (2023) | 1. Fasting blood sugar (FBS); 2.2-h postprandial glucose (PP2); 3. HbA1c; 4. Liver function (AST, ALT, ALP, GGT); 5. Renal function (BUN, cr, eGFR) | 1. FBS: 112.07 ± 18.10 → 108.79 ± 18.47 mg/dL (p = 0.556); 2. PP2: 210.00 ± 60.83 → 165.47 ± 43.90 mg/dL (p = 0.038); 3. HbA1c: 7.92 ± 0.63 → 6.50 ± 1.14 (p = 0.062); 4. AST, ALT, ALP, GGT: No significant change (p > 0.05); 5. BUN, cr, eGFR: No significant change (p > 0.05) | NR |
| Okabe et al. (2019) | 1. Completion rate of 1-year S-1 therapy; 2. Relative dose intensity; 3. AEs; 4. Recurrence-free survival (RFS); 5. Overall survival (OS) | 1. Completion rate: TG 54.5% vs. CG 50.9% (p = 0.35); 2. Relative dose intensity: TG 89.2% vs. CG 71.9% (p = 0.33); 3. Grade ≥3 AE: TG 45.5% vs. CG 54.5% (NS); 4. RFS: TG 59.9% vs. CG 70.6% (HR 1.44, p = 0.27); 5. OS: TG 63.9% vs. CG 78.1% (HR 1.68, p = 0.14) | TG 45.5% vs. CG 54.5% Grade ≥3; most common: leukopenia, neutropenia, appetite loss, diarrhea |
| Okugawa et al. (2024) | 1. C-reactive protein (CRP); 2. Albumin; 3. Prognostic Nutritional index (PNI); 4. Body composition by CT (PMI, IMAC, mIMAC); 5. Tumor markers (CEA, CA19-9) | 1. CRP: 0.36 → 0.15 mg/dL at 3 months (p < 0.001). metastatic group: 0.49 → 0.28 mg/dL (p = 0.0012); 2. Albumin: No significant change; 3. PNI: No significant change; 4. PMI preserved in CRP-decreased group vs. CRP-increased group (p = 0.028). IMAC & mIMAC NR; 5. Tumor markers: No improvement. CEA and CA19-9 increased | NR |
| Park et al. (2025) | 1. Menstrual pain (NRS); 2. PBAC; 3. EQ-5d-5l; 4. Hemoglobin; 5. Ultrasound (uterine size & MUSA findings) | 1. NRS: 7–8 → 1–2; 2. PBAC: >400 → 55; 3. EQ-5d-5l: 0.288 → 0.877; 4. Hemoglobin: 6–8 g/dL → 11 g/dL; 5. Uterine AP length: 8.7 cm → 7.28 cm ultrasound showed decreased adenomyosis area and restoration of normal myometrial tissue | NR |
| Qian et al. (2024) | 1. SNAQ score; 2. EORTC QLQ-C30 domains; 3. CTCAE | 1. SNAQ: improved significantly vs. placebo (15.2 ± 1.4 vs. 11.9 ± 1.8, p < 0.001); 2. QoL: multiple EORTC QLQ-C30 domains improved (p < 0.05); 3. CTCAE: Reduced chemotherapy-induced nausea/vomiting, diarrhea, anemia, neutropenia, leukopenia (all p < 0.05). Appetite benefit sustained longer when BIT administered first | Nausea/vomiting 9.1% vs. 62.1% (p < 0.001), diarrhea 12.1% vs. 44.8% (p = 0.004), anemia 15.2% vs. 41.4% (p = 0.021) |
| Qiu et al. (2024) | 1. QMG score; 2. MG-ADL score; 3. Symptom resolution 4. Pyridostigmine withdrawa | 1. QMG: 15 → 0; 2. MG-ADL: 11 → 0; 3. Complete clinical remission achieved by month 2, no relapse for 30 months; 4. Pyridostigmine successfully tapered and discontinued | NR |
| Seo et al. (2019) | 1. Daily urine output; 2. Self-voiding urine output; 3. Nelaton catheterization urine volume; 4. CRP level | 1. Daily urine output increased after treatment (exact value NR, described as “marked increase”); 2. Self-voiding urine output increased from almost none at baseline to majority of daily urine volume by day 10; 3. Nelaton catheterization volume decreased from daily requirement to near-zero by day 10; 4. CRP decreased from elevated level at admission to normal range (exact value NR) | NR |
| Takeuchi et al. (2017) | 1. AMS (aging males’ symptoms) score; 2. Serum total testosterone (TT) level | 1. AMS score improved 55 → 35 after treatment; 2. Serum TT remained unchanged at ∼349.7 ng/dL (baseline vs. post-treatment similar) | NR |
| Teng et al. (2016) | 1. Total effective rate | 1. Total effective rate during treatment: TG 97.36% (37/38) vs. CG 96.96% (32/33) (p > 0.05). After follow-up: TG 94.73% (36/38) vs. CG 78.78% (26/33) (p < 0.05) | NR |
| Terai et al. (2020) | 1. Semen volume (mL); 2. Sperm concentration (×106/mL); 3. Sperm motility (%); 4. Total motile sperm count (×106); 5. LH (mIU/mL); 6. FSH (mIU/mL); 7. Testosterone (ng/mL) | 1. Semen volume: TG 2.8 ± 1.2 vs. CG 2.7 ± 1.6; 2. Sperm concentration: TG 35.2 ± 35.4 vs. CG 49.1 ± 37.7; 3. Motility: TG 34.0 ± 17.6 vs. CG 31.4 ± 18.3; 4. Total motile sperm count: TG 27.1 ± 29.1 vs. CG 24.1 ± 21.9; 5. LH: TG 4.0 ± 1.8 vs. CG 3.8 ± 1.3; 6. FSH: TG 6.3 ± 3.4 vs. CG 5.4 ± 2.7; 7. Testosterone: TG 4.4 ± 1.0 vs. CG 4.6 ± 1.0 | NR |
| Tokumasu et al. (2025) | 1. Fatigue assessment scale (FAS) | 1. FAS: 35.9 ± 5.9 → 31.2 ± 9.4 (mean change −4.7.95% CI: 0.5–8.9) | NR |
| Wang (2016) | 1. Total effective rate | 1. TG 97.1% (34/35) vs. CG 74.2% (26/35) (p = 0.019) | NR |
| Wang et al. (2021) | 1. KPS score; 2. Serum VEGF (pg/mL); 3. Urine white blood cells (cells/µL); 4. Recurrence rate (6 and 12 months); 5. Adverse reactions | 1. KPS: 3 mo TG 83.54 ± 6.37 vs. CG 78.15 ± 10.31 (p = 0.028). 6 mo TG 90.92 ± 9.38 vs. CG 82.47 ± 6.26 (p = 0.034). 12 mo TG 92.23 ± 7.26 vs. CG 88.61 ± 11.32 (p = 0.421); 2. VEGF: 6 mo TG 329.5 ± 121.4 vs. CG 353.7 ± 125.6 (p = 0.042). 12 mo TG 290.3 ± 142.8 vs. CG 331.4 ± 135.2 (p = 0.027). 3 mo NS; 3. Urine WBC: 3 mo TG 20.14 ± 2.09 vs. CG 25.26 ± 4.27 (p = 0.037). 6 and 12 mo NS; 4. Recurrence: 6 mo TG 12.12% (4/33) vs. CG 18.75% (6/32) (p = 0.459). 12 mo TG 18.18% (6/33) vs. CG 25.00% (8/32) (p = 0.504); 5. See safety | Urgent urination: TG 36.36% vs. CG 78.13% (p = 0.043); Nausea/loss of appetite: TG 24.24% vs. CG 50.00% (p = 0.031); low fever: TG 15.15% vs. CG 25.00% (p = 0.321); hematuria: TG 18.18% vs. CG 34.38% (p = 0.137); abnormal urine routine: TG 21.21% vs. CG 46.88% (p = 0.029) |
| Watanabe and Maeda (2022) | 1. Physical activity (walking ex, vigorous activity time); 2. Dietary calorie intake; 3. EQ-VAS; 4. Days to walking milestones | 1. Walking ex at 10 weeks: TG 0.03 ± 0.01 vs. CG 0.02 ± 0.01 ex (p = 0.036). Vigorous activity at 8 weeks: TG 1.2 ± 0.7 vs. CG 0.6 ± 0.4 min (p = 0.026); 2. Dietary calories ↑: 10 wks TG 1374 ± 152 vs. CG 1165 ± 233 kcal/day (p = 0.016). Discharge TG 1352 ± 175 vs. CG 1204 ± 253 kcal/day (p = 0.035;. 3. EQ-VAS at 6 weeks: TG 80.4 ± 15.0 vs. CG 64.7 ± 23.9 (p = 0.038); 4. Days to walking with cane shorter in TG (p = 0.042) | TG: 10 AEs in 7 pts; 5 ADRs: Hypokalemia (2), dysuria (1), constipation (1), dry mouth (1). CG: 5 AEs in 5 pts |
| Wu et al. (2017) | 1. Wound healing time (days); 2. Wound flora composition (16S rRNA sequencing) | 1. Healing time: BYD 37.50 ± 2.34 vs. positive control 42.60 ± 5.27 (p < 0.05) vs. Negative control 32.16 ± 4.26 (p < 0.05); 2. Flora: BYD ↓ fusobacteria (0.04% vs. 5.29%, p < 0.05) & ↓ cyanobacteria (0.46% vs. 11.88%, p < 0.05) vs. positive control. BYD ↑ bacteroidetes (20.25% vs. 14.15%, p < 0.05) & ↑ proteobacteria (12.98% vs. 11.44%, p < 0.05) | NR |
| Xu et al. (2023) | 1. Clinical success rate; 2. Pathogen eradication rate; 3. CPIS; 4. Mechanical ventilation duration (days); 5.28-day mortality | 1. Clinical success: TG 40/83 (48.2%) vs. CG 28/85 (32.9%) (p = 0.044); 2. Pathogen eradication: TG 49/83 (59.0%) vs. CG 33/85 (38.9%) (p = 0.009); 3. CPIS: TG 8.9 ± 1.7 vs. CG 9.6 ± 2.5 (p = 0.003); 4. MV duration: TG 13.7 ± 6.4 days vs. CG 17.2 ± 7.2 days (p = 0.038); 5.28-day mortality: TG 11/83 (13.3%) vs. CG 18/85 (21.2%) (p > 0.05) | Hypoproteinemia: TG 17/83 (20.5%) vs. CG 18/85 (21.2%); no SAE; none related to BIT |
| Yang (2016) | 1. Clinical effective rate; 2. Endoscopic mucosal healing; 3.3-month recurrence rate | 1. Clinical effectiveness: Reflux symptoms 43/60 (71.67%) vs. 32/54 (59.26%) (p = 0.007). Esophageal symptoms 40/52 (76.92%) vs. 25/41 (60.98%) (p = 0.036). Extra-esophageal symptoms 21/38 (55.26) vs. 15/30 (50.00) (p = 0.419); 2. Endoscopic mucosal healing: TG showed significantly greater mucosal healing vs. CG (p = 0.031); 3. Recurrence after 3 months: TG 26/64 (40.63%) vs. CG 38/58 (65.52%) (p = 0.026) | TG: Nausea 3, appetite loss3 CG: Nausea 5, vomiting 2, constipation 1 |
| Zhang and Zhu (2015) | 1. Vaginal discharge duration (days); 2. Bleeding during scab-shedding (n/N); 3. Complete wound healing time (days) | 1. Vaginal discharge: TG 6.4 ± 3.46 days vs. CG 10.8 ± 6.14 days (p < 0.01); 2. Bleeding during scab-shedding: TG 1/30 (3.3%) more-than-menses, 4/30 (13.3%) equal, 25/30 (83.3%) less vs. CG 3/30 (10.0%) more, 8/30 (26.7%) equal, 19/30 (63.3%) less (p < 0.01); 3. Complete wound healing: TG 42 ± 7.75 days vs. CG 63 ± 5.29 days (p < 0.01) | NR |
| Zhou et al. (2022) | 1. Patient global impression of improvement (PGI-I); 2. ICIQ-SF score; 3.72-h urine leakage frequency | 1. PGI-I “very much better”: 68.89% at 1 month → 40.00% at 1 year. “no change”: 8.89% → 30.00%; 2. ICIQ-SF: 12.08 ± 5.10 → 2.82 ± 4.53 (1 month) → 4.90 ± 6.21 (1 year) (p < 0.05 vs. baseline. 1-year worse vs. 1-month, p < 0.05); 3.72-h urine leakage: 6.72 ± 6.61 → 1.32 ± 3.72 (1 month) → 3.00 ± 6.16 (1 year) (p < 0.05 vs. baseline. 1-year worse vs. 1-month, p < 0.05) | NR |
AE, adverse event; ADR, adverse drug reaction; BIT, Bojungikki-tang; CAT, COPD, assessment test; CBD, Cheonwangbosim-dan; CG, control group; CPIS, clinical pulmonary infection score; CRP, C-reactive protein; CTCAE, common terminology criteria for adverse events; DCR, disease control rate; DLQI, dermatology life quality index; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; EQ-5D, EuroQol 5-Dimension; EQ-VAS, EuroQol visual analogue scale; ICIQ-SF, International Consultation on Incontinence Questionnaire–Short Form; KOG, Kyungok-go; KPS, karnofsky performance status; mMRC, modified Medical Research Council; NR, not reported; NS, not significant; ORR, objective response rate; QOL, quality of life; RECIST, response evaluation criteria in solid tumors; RFS, recurrence-free survival; TG, treatment group; TNSS, total nasal symptom score; VRE, vancomycin-resistant Enterococci.
3.5. Safety reporting and adverse events
Safety reporting was uneven across the included studies, and many did not provide detailed AE information (Akita et al., 2019; Chen et al., 2024; Chen et al., 2018; Hamada et al., 2018; Huang, 2015; Huang et al., 2025; Kim et al., 2023; Kim and Keum, 2015; Lee et al., 2021; Lee et al., 2015; Lee et al., 2018; Lee, 2017; Lee et al., 2019; Li et al., 2021a; Li et al., 2021b; Minagawa et al., 2019; Ni et al., 2021; Oh et al., 2023; Okugawa et al., 2024; Park et al., 2025; Qiu et al., 2024; Seo et al., 2019; Takeuchi et al., 2017; Teng et al., 2016; Terai et al., 2020; Tokumasu et al., 2025; Wang, 2016; Wu et al., 2017; Zhang and Zhu, 2015; Zhou et al., 2022). Among studies that reported adverse events (AEs), events were typically mild to moderate, with few reports suggestive of BIT-related toxicity. Transient liver dysfunction was described in one participant and resolved after discontinuation (Edahiro et al., 2022), and mild liver dysfunction of uncertain causality was noted in a COPD study (Hamada et al., 2022). Several controlled studies in oncology and postoperative populations reported lower overall AE rates or fewer treatment-related symptoms in the BIT groups (Hu et al., 2024; Li et al., 2016; Lu et al., 2021; Qian et al., 2024; Wang et al., 2021), while one gastric cancer trial reported comparable rates of grade ≥3 events between groups (Okabe et al., 2019). In infection-related settings, hypokalemia was reported in one case (Kohno et al., 2021), and a hospital-acquired pneumonia trial reported no serious AEs and no events judged related to treatment (Xu et al., 2023). In trials involving allergic rhinitis and atopic dermatitis–associated anorexia, mild events were reported without meaningful between-group differences (Lee et al., 2025; Lee et al., 2024), and a long COVID trial reported only mild AEs with largely stable laboratory parameters (Kim et al., 2024). In addition, a geriatric reflux esophagitis study reported mild gastrointestinal symptoms such as nausea and appetite loss, without evidence of serious treatment-related toxicity (Yang, 2016). A postoperative hip fracture trial recorded several events considered adverse drug reactions, including hypokalemia, dysuria, constipation, and dry mouth (Watanabe and Maeda, 2022). An advanced non-small-cell lung cancer (NSCLC) study conducted alongside atezolizumab reported a numerically higher AE incidence in the BIT group, including one grade ≥3 immune-related pneumonia case (Ko et al., 2025), although most events were mild to moderate and overall differences were not statistically significant (Table 3).
4. Discussion
This scoping review mapped 47 clinical studies on BIT published since 2015 and found a broad but uneven evidence landscape across clinical areas. Rather than supporting a single disease-centered indication, the literature concentrates on contexts where symptom burden and recovery are central, with oncology representing the largest cluster of clinical use. This pattern is consistent with recent oncology-focused synthesis work highlighting supportive care, symptom control, and immune-related outcomes as recurring themes in human research on BIT (Cho et al., 2024). Taken together, the evidence base appears to have expanded in scope without a parallel convergence on standardized trial models, formulations, and outcome frameworks, which has implications for both interpretability and future trial prioritization.
The predominance of oncology studies in the present review is clinically meaningful. Among the 13 cancer-related studies, BIT was typically evaluated as an adjunctive intervention across distinct oncology treatment contexts, including chemotherapy or chemoradiotherapy for solid tumors, perioperative recovery, hematologic supportive care, and immune checkpoint inhibitor combination treatment, rather than as a stand-alone antitumor intervention (Edahiro et al., 2022; Hu et al., 2024; Ko et al., 2025; Lee et al., 2021; Lee et al., 2015; Lee, 2017; Lee et al., 2019; Li et al., 2016; Minagawa et al., 2019; Okabe et al., 2019; Okugawa et al., 2024; Qian et al., 2024; Wang et al., 2021). Therefore, this oncology cluster should not be interpreted as a homogeneous clinical category. These treatment contexts imply distinct clinical rationales and outcome priorities: chemotherapy- or chemoradiotherapy-associated studies mainly emphasized appetite, fatigue, nutritional status, quality of life, inflammatory markers, and treatment-related symptoms; perioperative or postoperative studies focused more on recovery trajectories and treatment tolerance; immunotherapy-combination studies incorporated immune response and progression-related outcomes; and the hematologic supportive-care context focused mainly on quality of life and symptom burden. This pattern indicates that BIT has been positioned primarily to address treatment- and disease-associated functional decline, where patient-centered improvements may be clinically relevant even when tumor-control endpoints are not the primary focus or are inconsistently assessed. A similar emphasis is described in broader discussions of Kampo or East Asian botanical drug–based supportive cancer care, where interventions are more often evaluated for symptom burden, functional resilience, and treatment-related adverse effects than for definitive oncologic endpoints such as survival or progression measures (Motoo and Cameron, 2022; Oteki et al., 2016; Okada et al., 2020). The emergence of immune checkpoint inhibitor combination studies suggests a newer research direction, but it remains uncertain whether such approaches will generate clinically decisive evidence (Ko et al., 2025; Cho et al., 2025).
Respiratory indications provide further support for a shared immune–inflammatory axis across disease systems. Respiratory indications accounted for 6 of 47 studies (12.8%). The included studies spanned chronic inflammatory airway disease, infection-related pneumonia, and post-viral syndromes—clinical contexts typically characterized by immune dysregulation and sustained inflammatory stress rather than isolated disturbances in pulmonary mechanics (Hamada et al., 2018; Hamada et al., 2022; Huang et al., 2025; Kim et al., 2024; Tokumasu et al., 2025, Xu et al., 2023). Accordingly, several studies incorporated inflammatory markers or immune profiles alongside conventional respiratory assessments. Outcome evaluation also extended beyond spirometric indices to include broader functional measures such as dyspnea, activity, and fatigue trajectories, particularly in post-viral recovery contexts (Hamada et al., 2018; Xu et al., 2023; Tokumasu et al., 2025). Similar to oncology, this pattern suggests that BIT has been investigated less as a disease-specific pulmonary modifier and more as a regulator of host immune balance during periods of inflammatory burden and physiologic vulnerability.
Beyond oncology and respiratory disease, a comparable recovery phenotype was evident across postoperative and convalescent settings. In the hip-fracture RCT in older adults, BIT was evaluated during postoperative rehabilitation and was associated with improvements in physical activity and appetite (Watanabe and Maeda, 2022). Similarly, the 2025 exploratory pilot in post-COVID-19 condition tracked fatigue trajectories over an 8-week treatment period (Tokumasu et al., 2025). This endpoint profile aligns with broader discussions of traditional botanical preparations in supportive care, where symptom burden, nutritional intake, and functional resilience are commonly prioritized, particularly for fatigue- and anorexia-related domains (Motoo and Cameron, 2022; Zedler et al., 2024). Recent reviews of post-COVID fatigue management likewise highlight functional recovery and persistent symptom burden as central targets, mirroring the tendency of respiratory and post-viral studies in this review to converge on fatigue and activity outcomes (Chen et al., 2025). Taken together, these patterns suggest that despite diagnostic diversity, the included conditions share a common clinical expression of reduced functional reserve and delayed recovery, positioning BIT as a potential resilience-enhancing intervention across physiologic vulnerability states. This recovery-oriented framing should be interpreted as an authors’ interpretive synthesis based on recurring populations, outcomes, and clinical contexts, rather than as an empirically confirmed mechanism or treatment effect.
Despite the growth of controlled trials, the included literature showed marked heterogeneity in how BIT was delivered and evaluated, limiting cross-study interpretability. BIT was used as monotherapy in 26 of 47 studies (55.3%), while 21 studies (44.7%) assessed it as an adjunct to conventional care, rehabilitation, pharmacotherapy, or other integrative interventions. Formulation varied substantially: granule preparations were used in 22 studies (46.8%) (Akita et al., 2019; Edahiro et al., 2022; Hamada et al., 2018; Hamada et al., 2022; Huang et al., 2025; Kim et al., 2024; Kitahara et al., 2021; Ko et al., 2025; Kohno et al., 2021; Lee et al., 2025; Lee et al., 2015; Lee, 2017; Lee et al., 2024; Minagawa et al., 2019; Oh et al., 2023; Okabe et al., 2019; Okugawa et al., 2024; Takeuchi et al., 2017; Terai et al., 2020; Tokumasu et al., 2025; Watanabe and Maeda, 2022; Wu et al., 2017) and decoctions in 20 studies (42.6%) (Chen et al., 2024; Chen et al., 2018; Hu et al., 2024; Huang, 2015; Kim et al., 2023; Lee et al., 2021; Li et al., 2021a; Li et al., 2021b; Li et al., 2016; Lu et al., 2021; Ni et al., 2021; Park et al., 2025; Qiu et al., 2024; Seo et al., 2019; Teng et al., 2016; Wang, 2016; Wang et al., 2021; Xu et al., 2023; Zhang and Zhu, 2015; Zhou et al., 2022), together accounting for 89.4% of interventions. However, these categories may understate clinically important differences, because granule-based studies more often used fixed commercial products, whereas decoction-based studies frequently employed modified prescriptions with additional botanical drugs or flexible adjustment. Whereas granule-based studies more often used fixed commercial products.
This distinction is clinically relevant because standardized granules and highly modified decoctions may represent different pharmacological exposures, dose–exposure assumptions, and levels of reproducibility. In addition, formulation type appeared to overlap with country of origin and study design, as Japanese studies more often used fixed granule products whereas several Chinese studies used modified decoction-based prescriptions, and South Korean studies included a larger proportion of case-based reports. These differences may reflect distinct prescribing traditions, regulatory environments, reimbursement systems, and research infrastructures across East Asian healthcare settings, and may confound direct interpretation of outcomes across formulation categories. Therefore, geographic clustering should be considered when interpreting formulation choice, study design, outcome selection, AE reporting, and the generalizability of the mapped evidence. Comparator strategies were similarly diverse, spanning placebo-controlled designs, usual-care comparisons, active co-interventions, and uncontrolled observations. As a result, identical preparation labels often represented different compositional and dosing realities, and findings were difficult to contrast directly even within the same disease system. Under these conditions, the evidence is best interpreted as mapping where and how BIT has been studied rather than as supporting a single transferable estimate of effect across indications.
Outcome reporting varied widely across the included studies, reflecting both the broad range of indications and the lack of a shared measurement framework. Many trials relied on symptom-centered patient-reported outcomes and condition-specific clinical scores (Kim et al., 2023; Kim and Keum, 2015; Chen et al., 2024; Chen et al., 2018; Zhou et al., 2022; Seo et al., 2019), often paired with generic or disease-specific quality-of-life instruments (Edahiro et al., 2022; Hamada et al., 2018; Hu et al., 2024; Kim et al., 2023; Kim et al., 2024; Lee et al., 2025; Lee et al., 2015; Lee et al., 2018; Lee et al., 2024; Li et al., 2016; Park et al., 2025; Qian et al., 2024; Watanabe and Maeda, 2022). Functional performance endpoints were common in respiratory and postoperative settings (Hamada et al., 2018; Hamada et al., 2022; Watanabe and Maeda, 2022), whereas neurologic and neuromuscular studies more often used disease-specific functional scales (Kitahara et al., 2021; Li et al., 2021a; Li et al., 2021b; Qiu et al., 2024). Biomarkers were frequently incorporated, spanning inflammatory markers, nutritional indices, immune profiles, and metabolic or endocrine parameters (Akita et al., 2019; Hu et al., 2024; Huang, 2015; Ko et al., 2025; Lee et al., 2025; Li et al., 2016; Oh et al., 2023; Okugawa et al., 2024; Takeuchi et al., 2017; Terai et al., 2020), with a smaller subset reporting microbiome-related measures (Huang et al., 2025; Lee et al., 2025; Ni et al., 2021; Wu et al., 2017). This breadth suits a scoping review approach (Arksey and O’Malley, 2005; Tricco et al., 2018; Peters et al., 2020), but substantial within-category heterogeneity in instruments, follow-up windows, and analytic handling limits comparability. Recent reporting guidance emphasizes that outcomes should be defined explicitly with prespecified time points and transparent analytic rules to support interpretation and synthesis, yet these elements were inconsistently described in the included literature (Butcher et al., 2022). As a result, outcome themes can be mapped, but effects remain difficult to synthesize across studies.
Safety reporting was a clear weak point in the included literature. Many studies did not provide detailed adverse-event information, and structured approaches to causality assessment were rarely described (Akita et al., 2019; Chen et al., 2024; Chen et al., 2018; Hamada et al., 2018; Huang, 2015; Huang et al., 2025; Kim et al., 2023; Kim and Keum, 2015; Lee et al., 2021; Lee et al., 2015; Lee et al., 2018; Lee, 2017; Lee et al., 2019; Li et al., 2021a; Li et al., 2021b; Minagawa et al., 2019; Ni et al., 2021; Oh et al., 2023; Okugawa et al., 2024; Park et al., 2025; Qiu et al., 2024; Seo et al., 2019; Takeuchi et al., 2017; Teng et al., 2016; Terai et al., 2020; Tokumasu et al., 2025; Wang, 2016; Wu et al., 2017; Zhang and Zhu, 2015; Zhou et al., 2022). Among the 23 RCTs, 13 studies provided some structured AE information, whereas 10 studies did not provide detailed AE information. Incomplete reporting of botanical drug composition, product characteristics, processing and extraction information, concomitant medications, AEs, and interaction-related safety data limited the direct interpretation and comparability of safety findings across studies. When AEs were reported, they were usually mild to moderate and serious events appeared uncommon, but this impression is constrained by incomplete documentation rather than robust negative evidence. Therefore, the current safety evidence remains insufficient, and underreporting may have biased the apparent tolerability of BIT. Current trial standards, including CONSORT Harms 2022, increasingly expect transparent harms reporting, including how events are defined, actively collected, graded, and attributed; without those details, tolerability signals may be underestimated and potential drug–botanical preparation interaction risks can be difficult to evaluate, particularly with complex co-medication exposure (Junqueira et al., 2023). Reporting assessments in Chinese botanical drug trials similarly suggest persistent shortcomings in intervention and safety reporting despite dedicated guideline extensions (Wang et al., 2024). Future BIT trials should therefore document concomitant medications, monitoring schedules, discontinuations, adverse-event attribution, and interaction-related safety data more systematically, particularly in oncology and multimorbidity contexts.
Several implications emerge from this mapped evidence. From a methodological perspective, differences in intervention delivery, comparator selection, outcome definition, and safety reporting limit cross-study synthesis and indicate that the current literature does not yet support a single transferable estimate of effect across disease categories. Because this was a scoping review, we did not conduct a formal risk-of-bias assessment, certainty-of-evidence appraisal, or structured reporting quality assessment, which should be regarded as an important limitation, particularly because nearly half of the included studies were RCTs. In addition, the lack of explicit primary and secondary outcome designation in many studies limited the ability to construct a structured outcome hierarchy for future core outcome development. Although all included studies were published in peer-reviewed journals, variation in journal visibility and reporting standards may have influenced the completeness of methodological and safety reporting. Therefore, the findings should be interpreted as a map of the clinical evidence landscape rather than as a judgment on the reliability, effectiveness, or safety of BIT. These features are consistent with a research field that has expanded across multiple clinical areas without a parallel convergence on unified trial models (Zhong et al., 2010). Nevertheless, despite these methodological constraints, the literature reveals a set of recurring clinical patterns. Across oncology and respiratory disease in particular, studies repeatedly situate BIT within contexts characterized by immune–inflammatory burden and reduced physiologic reserve. Fatigue, appetite disturbance, and quality-of-life impairment appear consistently as dominant outcome domains, suggesting that many of the included populations share a common clinical phenotype of physiologic vulnerability and delayed recovery. In this sense, oncology supportive care, respiratory and post-viral conditions, and postoperative recovery contexts appear to converge on a similar therapeutic framing.
Taken together, these repeated patterns suggest that although the evidence base remains methodologically heterogeneous, BIT is being positioned across multiple disease systems as a recovery-oriented intervention that may modulate immune–inflammatory stress and support restoration of functional resilience. Future studies would therefore benefit from tighter specification of formulation, clearer differentiation between fixed commercial products and modified prescriptions, and adoption of shared recovery-oriented outcomes such as fatigue, appetite, physical activity, and quality of life. Standardized harms reporting, clear separation of treatment duration and post-treatment follow-up, and prespecified time points would further strengthen interpretability. Equally important, future studies should avoid treating BIT as a uniform intervention unless botanical drug composition, product characteristics, processing, extraction, and dosage are sufficiently comparable. A strategic shift toward fewer, larger, and methodologically aligned trials within these recurring clinical clusters may clarify the potential recovery-oriented role of BIT more effectively than continued expansion into rarely studied or methodologically isolated indications.
5. Conclusion
This scoping review identified 47 clinical studies on BIT published since 2015 and found that the current evidence base is concentrated in supportive-care contexts rather than in a single disease-specific indication. Cancer-related conditions were the largest clinical cluster, and nearly half of all included studies were RCTs, but substantial heterogeneity remained in formulation, comparator strategy, treatment duration, and outcome selection. Across indications, the most consistent research theme was not disease modification itself, but improvement in fatigue, appetite, functional recovery, quality of life, and treatment tolerance. These findings suggest that, based on research volume and thematic convergence rather than demonstrated efficacy, the most productive next step is not broader exploratory use across many unrelated conditions, but more rigorous and standardized trials in a limited number of recurrently studied clinical scenarios, particularly oncology supportive care and other recovery-focused settings. However, the frequency of investigation should not be interpreted as evidence of benefit, and future studies are needed to determine whether BIT provides clinically meaningful effects in these contexts.
Funding Statement
The author(s) declared that financial support was received for this work and/or its publication. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (RS-2025-02308386).
Footnotes
Edited by: Fulun Li, Shanghai University of Traditional Chinese Medicine, China
Reviewed by: Kuei-Hung Lai, Taipei Medical University, Taiwan
Picheswara Rao Polu, Lovely Professional University, India
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Author contributions
S-DK: Conceptualization, Visualization, Data curation, Writing – original draft, Formal Analysis. BL: Methodology, Validation, Formal Analysis, Writing – review and editing, Data curation. Y-CP: Writing – review and editing, Validation. YL: Funding acquisition, Writing – review and editing, Conceptualization, Methodology, Supervision.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2026.1831561/full#supplementary-material
References
- Akita S., Namiki T., Kawasaki Y., Rikihisa N., Ogata H., Tokumoto H., et al. (2019). The beneficial effect of traditional Japanese herbal (Kampo) medicine, hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang), for patients with chronic wounds refractory to conventional therapies: a prospective, randomized trial. Wound Repair Regeneration 27, 672–679. 10.1111/wrr.12753 [DOI] [PubMed] [Google Scholar]
- Arksey H., O’Malley L. (2005). Scoping studies: towards a methodological framework. Int. J. Soc. Res. Methodol. 8, 19–32. 10.1080/1364557032000119616 [DOI] [Google Scholar]
- Butcher N. J., Monsour A., Mew E. J., Chan A.-W., Moher D., Mayo-Wilson E., et al. (2022). Guidelines for reporting outcomes in trial reports: the CONSORT-Outcomes 2022 extension. JAMA 328, 2252–2264. 10.1001/jama.2022.21022 [DOI] [PubMed] [Google Scholar]
- Chen Y., Shergis J. L., Wu L., Yu X., Zeng Q., Xu Y., et al. (2016). A systematic review and meta-analysis of the herbal formula Buzhong Yiqi Tang for stable chronic obstructive pulmonary disease. Complementary Ther. Med. 29, 94–108. 10.1016/j.ctim.2016.09.017 [DOI] [PubMed] [Google Scholar]
- Chen Z., Huang H., Chen Q. Y. (2018). Effect of modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrical stimulation on early stage postpartum pelvic floor dysfunction. Zhongguo Zhong Yao Za Zhi 43, 2391–2395. 10.19540/j.cnki.cjcmm.20180305.001 [DOI] [PubMed] [Google Scholar]
- Chen L., Wang D., Cai J., Yin C., Yan X. (2024). Effects of Chinese herbal treatment and biofeedback electrical stimulation on pelvic floor muscle strength and quality of life in patients with postpartum stress urinary incontinence. Afr. J. Reproductive Health 28, 196–204. 10.29063/ajrh2024/v28i11.19 [DOI] [PubMed] [Google Scholar]
- Chen Y., Zhang C., Feng Y. (2025). Medicinal plants for the management of post-COVID-19 fatigue: a literature review on the role and mechanisms. J. Traditional Complementary Med. 15, 15–23. 10.1016/j.jtcme.2024.05.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cho E., Na S. W., Jeong M. K. (2024). Therapeutic and immunomodulatory effects of Bojungikki-tang on cancer: a scoping review. BMC Cancer 24, 1169. 10.1186/s12885-024-12924-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cho E., Yi J. M., Chun J., Jang H., Yoon S. H., Lee S. H., et al. (2025). Efficacy and safety of herbal Medicine Bojungikki-tang in combination with Pembrolizumab versus Pembrolizumab monotherapy for stage IV non-small cell lung cancer: study protocol for a randomized, open-label, double-arm, multicenter trial. Integr. Cancer Ther. 24, 15347354251319339. 10.1177/15347354251319339 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edahiro Y., Koike M., Nojiri S., Harada Y., Gotoh A., Fujibayashi K., et al. (2022). A pilot study examining the efficacy of hochuekkito for improving quality of life in patients with myeloproliferative neoplasms. Jpn. Journal Clinical Oncology 52, 880–886. 10.1093/jjco/hyac076 [DOI] [PubMed] [Google Scholar]
- Gong H., Qin F., He H. (2018). Herbal Formula modified buzhong-yiqi-tang for functional constipation in adults: a meta-analysis of randomized controlled trials. Evidence-based complementary Altern. Med. 2018, 9602525. 10.1155/2018/9602525 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guo C. Y., Ma Y. J., Liu S. T., Zhu R. R., Xu X. T., Li Z. R., et al. (2022). Traditional Chinese medicine and sarcopenia: a systematic review. Front. Aging Neurosci. 14, 872233. 10.3389/fnagi.2022.872233 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamada H., Sekikawa K., Murakami I., Aimoto K., Kagawa K., Sumigawa T., et al. (2018). Effects of Hochuekkito combined with pulmonary rehabilitation in patients with chronic obstructive pulmonary disease. Exp. Ther. Med. 16, 5236–5242. 10.3892/etm.2018.6837 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamada H., Sekikawa K., Okusaki K., Dodo T., Kagawa K., Sumigawa T., et al. (2022). Hochuekkito combined with pulmonary rehabilitation in apathetic patients with chronic obstructive pulmonary disease: a randomized controlled pilot trial. J. Clinical Medicine 11, 5673. 10.3390/jcm11195673 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heinrich M., Jalil B., Abdel-Tawab M., Echeverria J., Kulić Ž., Mcgaw L. J., et al. (2022). Best Practice in the chemical characterisation of extracts used in pharmacological and toxicological research—The ConPhyMP—Guidelines12. Front. Pharmacol. 13, 953205. 10.3389/fphar.2022.953205 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hu Q., Chen X. P., Tang Z. J., Zhu X. Y., Liu C. (2024). Therapeutic effects of Buzhong Yiqi decoction in patients with spleen and stomach qi deficiency after routine surgery and chemotherapy for colorectal cancer. World J. Gastrointest. Surg. 16, 2183–2193. 10.4240/wjgs.v16.i7.2183 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang P. (2015). Effect of modified Buzhong Yiqi Decoction on blood glucose levels of diabetic patients with different TCM constitution. Clin. Medical & Engineering [lin Chuang Yi Xue Gong Cheng] 22, 596–597. [Google Scholar]
- Huang Q., Wang F., Zhu J., Li Z. (2025). Buzhong Yiqi Granules Increase Alistipes in the Gut to Alleviate Osa Lung-Spleen Qi Deficiency Syndrome. [Google Scholar]
- Junqueira D. R., Zorzela L., Golder S., Loke Y., Gagnier J. J., Julious S. A., et al. (2023). CONSORT Harms 2022 statement, explanation, and elaboration: updated guideline for the reporting of harms in randomized trials. J. Clin. Epidemiol. 158, 149–165. 10.1016/j.jclinepi.2023.04.005 [DOI] [PubMed] [Google Scholar]
- Kim Y., Keum S. (2015). Effect of Baenong Ickki San on chronic Prostatitis/Chronic pelvic pain syndrome: a case series. J. Intern. Korean Med. 36, 391–399. [Google Scholar]
- Kim J., Kim H., Kim K. H. (2017). Effects of bu-zhong-yi-qi-tang for the treatment of functional dyspepsia: a feasibility study protocol. Integr. Med. Res. 6, 317–324. 10.1016/j.imr.2017.07.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim N., Kim T., Kwon M., Im Y., Lee D. (2023). A case of postherpetic Neuralgia treated with Korean medicine, including soeumin Bojungikgitang-gagambang. J. Intern. Korean Med. 44, 920–928. 10.22246/jikm.2023.44.5.920 [DOI] [Google Scholar]
- Kim T. H., Yoon J., Kim S., Kang B. K., Kang J. W., Kwon S. (2024). Herbal medicines for long COVID: a phase 2 pilot clinical study. Heliyon 10, e37920. 10.1016/j.heliyon.2024.e37920 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kitahara M., Takayama S., Akaishi T., Kikuchi A., Ishii T. (2021). Hochuekkito can prevent the colonization of Methicillin-Resistant Staphylococcus aureus in upper respiratory tract of acute stroke patients. Front. Pharmacol. 12, 683171. 10.3389/fphar.2021.683171 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ko M. M., Na S. W., Yi J. M., Jang H., Choi C. M., Lee S. H., et al. (2025). Effects of Bojungikki-tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors: a randomized pilot study. BMC Cancer 25, 1229. 10.1186/s12885-025-14629-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohno J., Kawamura T., Kikuchi A., Akaishi T., Takayama S., Ishii T. (2021). A Japanese traditional medicine Hochuekkito promotes negative conversion of vancomycin-resistant Enterococci. Sci. Rep. 11, 11300. 10.1038/s41598-021-90890-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuroiwa A., Liou S., Yan H., Eshita A., Naitoh S., Nagayama A. (2004). Effect of a traditional Japanese herbal medicine, hochu-ekki-to (Bu-Zhong-Yi-Qi Tang), on immunity in elderly persons. Int. Immunopharmacol. 4, 317–324. 10.1016/j.intimp.2003.12.004 [DOI] [PubMed] [Google Scholar]
- Kwon C.-Y., Lee B., Lee B.-J., Kim K.-I., Jung H.-J. (2021). Herbal medicine compared to placebo for chronic obstructive pulmonary disease: a systematic review and meta-analysis. Front. Pharmacol. 12, 717570. 10.3389/fphar.2021.717570 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee S. (2017). A case report of chemotherapy-induced alopecia treated with Bojungikki-tang. J. Intern. Korean Med. 38, 235–239. 10.22246/jikm.2017.38.2.235 [DOI] [Google Scholar]
- Lee E., Choi Y., Kwak M. (2015). Effects of Bojungikki-tang extracts on improvement of fatigue and quality of life in patient with cervical cancer after concurrent chemoradiation therapy: a case. J. EAST - WEST Med. 40, 25–34. [Google Scholar]
- Lee L. W., Lin H. J., Huang S. T. (2018). Management of IFN-beta-induced flu-like symptoms with Chinese herbal medicine in a patient with multiple sclerosis: a case report. Complementary Ther. Med. 36, 123–128. 10.1016/j.ctim.2017.12.011 [DOI] [PubMed] [Google Scholar]
- Lee S., Lee Y., Lee J. (2019). A case report of sweating and palpitation due to chemotherapy for cancer in a soeumin patient with primary central nervous System lymphoma. J. Sasang Const. Immune Med. 31, 31–40. 10.7730/JSCM.2019.31.2.31 [DOI] [Google Scholar]
- Lee B. J., Kim K. I., Choi C. W., Kim J. Y., Lee J. H. (2021). Long-term progression-free survival in a patient with advanced non-small-cell lung cancer treated with low-dose gefitinib and traditional herbal medicine: a case report. Med. Baltim. 100, e24292. 10.1097/md.0000000000024292 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee S. W., Woo S. C., Lyu Y. R., Yang W. K., Kim S. H., Kim J. H., et al. (2024). “Efficacy and safety of Bojungikgi-Tang for persistent allergic rhinitis: a randomized, Double-Blinded, Placebo-Controlled, phase II trial. Healthcare 12 1017. 10.3390/healthcare12101017 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee B., Ko M. M., Ahn Y. M., Park H. J., Jung S. Y., Jung H. A., et al. (2025). Effect of herbal medicine Bojungikgi-tang on gut microbiome and symptoms in anorexic patients with atopic dermatitis: a randomized controlled trial. Front. Pharmacology 16, 1593477. 10.3389/fphar.2025.1593477 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li X. H., Yang H., Wang J., Li Y. F. (2016). Effect of modified Buzhong Yiqi Decoction on postoperative chemotherapy of lung carcinoma. J. hunan Univ. Chin. Med. 36, 48–51. [Google Scholar]
- Li H., Huang H., Long W., Zuo J., Huang H. (2021a). Herbal medicine significantly improved muscle function in a patient with type 1 facioscapulohumeral muscular dystrophy: a case report. Explore (NY) 17, 247–251. 10.1016/j.explore.2020.05.009 [DOI] [PubMed] [Google Scholar]
- Li J., Qi G., Liu Y. (2021b). Effect of Buzhong Yiqi decoction on anti-acetylcholine receptor antibody and clinical status in juvenile ocular myasthenia gravis. Med. Baltim. 100, e27688. 10.1097/md.0000000000027688 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lu B., DU J., Wu X. (2021). The effects of modified Buzhong Yiqi decoction combined with Gangtai ointment on the wound healing and anal function in circumferential mixed hemorrhoid patients. Am. J. Transl. Res. 13, 8294–8301. [PMC free article] [PubMed] [Google Scholar]
- Minagawa T., Domen T., Suzuki T., Ueno M., Nagai T., Ogawa T., et al. (2019). Effectiveness of hochuekkito (japanese herbal medicine) for general fatigue after introduction of enzalutamide in three cases of castration-resistant prostate cancer. Nihon Hinyokika Gakkai Zasshi 110, 86–91. 10.5980/jpnjurol.110.86 [DOI] [PubMed] [Google Scholar]
- Motoo Y., Cameron S. (2022). Kampo medicines for supportive care of patients with cancer: a brief review. Integr. Med. Res. 11, 100839. 10.1016/j.imr.2022.100839 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ni Z., Cheng W., Ding J., Yao R., Zhang D., Zhai D., et al. (2021). Impact of Buzhong yiqi prescription on the gut microbiota of patients with obesity manifesting polycystic ovarian syndrome. Evidence-Based Complementary Altern. Med. 2021, 6671367. 10.1155/2021/6671367 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oh S., Jung W., Song M., Noh J., Ahn Y., Ahn S., et al. (2023). A retrospective Study of the safety and effect of Co-administration of glucose-lowering medication and Bojungikgi-tang on blood glucose level in patients with type 2 diabetes mellitus. J. Intern. Korean Med. 44, 354–365. 10.22246/jikm.2023.44.3.354 [DOI] [Google Scholar]
- Okabe H., Kinjo Y., Obama K., Hosogi H., Hata H., Asao Y., et al. (2019). A randomized phase II Study of S-1 adjuvant chemotherapy with or without hochu-ekki-to, a Japanese herbal medicine, for stage II/III gastric cancer: the KUGC07 (SHOT) trial. Front. Oncol. 9, 294. 10.3389/fonc.2019.00294 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okada K.-I., Kawai M., Hirono S., Miyazawa M., Kitahata Y., Kobayashi R., et al. (2020). Impact of Ninjin’Yoeito on fatigue in patients receiving nab-paclitaxel plus gemcitabine therapy: a prospective, Single-Arm, phase II open label, nonrandomized, historically-controlled Study. Curr. Ther. Res. 93, 100605. 10.1016/j.curtheres.2020.100605 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okugawa Y., Shirai Y., Fukumori K., Kitajima T., Shimura T., Imaoka H., et al. (2024). Effect of the Japanese herbal medicine Hochuekkito for systemic inflammation, prognostic nutrition index, and body composition status in patients with gastrointestinal cancer. Clin. Nutr. ESPEN 63, 757–767. 10.1016/j.clnesp.2024.08.004 [DOI] [PubMed] [Google Scholar]
- Oteki T., Ishikawa A., Sasaki Y., Ohara G., Kagohashi K., Kurishima K., et al. (2016). Effect of rikkunshi-to treatment on chemotherapy-induced appetite loss in patients with lung cancer: a prospective study. Exp. Ther. Med. 11, 243–246. 10.3892/etm.2015.2903 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park H., Jeong H., Kim K. H., Yang S. J., Roh S. (2025). Management of symptoms of suspected adenomyosis uteri using herbal medicine modified Bojungikgi-tang: a case report with ultrasound monitoring. Front. Med. 12, 1679449. 10.3389/fmed.2025.1679449 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peters M. D. J., Marnie C., Tricco A. C., Pollock D., Munn Z., Alexander L., et al. (2020). Updated methodological guidance for the conduct of scoping reviews. JBI Evid. Synth. 18, 2119–2126. 10.11124/JBIES-20-00167 [DOI] [PubMed] [Google Scholar]
- Qian J., Yan X. U., Hongyi H. U., Aiguang Z. (2024). Clinical efficacy and safety evaluation of Buzhongyiqi pills on appetite improvement in patients with colorectal cancer receiving chemotherapy: a pilot randomized cross-over clinical trial. J. Traditional Chin. Med. 44, 1254–1267. 10.19852/j.cnki.jtcm.20240806.005 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qiu H., Chen X., Zhang L., Zhang Q., Qiu C., Li J. (2024). Clinical remission of moderate generalized myasthenia gravis through exclusive use of Buzhong Yiqi decoction: a case report. Explore (NY) 20, 588–591. 10.1016/j.explore.2024.05.004 [DOI] [PubMed] [Google Scholar]
- Rivera D., Allkin R., ObóN C., Alcaraz F., Verpoorte R., Heinrich M. (2014). What is in a name? The need for accurate scientific nomenclature for plants. J. Ethnopharmacol. 152, 393–402. 10.1016/j.jep.2013.12.022 [DOI] [PubMed] [Google Scholar]
- Satoh N., Sakai S., Kogure T., Tahara E., Origasa H., Shimada Y., et al. (2005). A randomized double blind placebo-controlled clinical trial of Hochuekkito, a traditional herbal medicine, in the treatment of elderly patients with weakness N of one and responder restricted design. Phytomedicine 12, 549–554. 10.1016/j.phymed.2004.06.014 [DOI] [PubMed] [Google Scholar]
- Seo Y., Kim S., Kim G., Cho K., Moon S., Jung W., et al. (2019). A case of stroke patient complaining dysuria and urination pain caused by repeated urinary tract infection that do not respond to antibiotics treated with Bojungiki-tang. J. Soc. Stroke Korean Med. 20, 17–24. [Google Scholar]
- Takeuchi H., Matsusita K., Aoyagi T. (2017). One case of male late-onset hypogonadism syndrome that was benefited by middle-reinforcing and qi-benefiting decoction (Hochu-Ekki-To). J. Sex. Med. 14, S90–S91. 10.1016/j.jsxm.2016.11.205 [DOI] [Google Scholar]
- Teng H., Liu Y. L., Wang J. L. (2016). Clinical observation on therapy of integrated medicine in the treatment of perimenopausal uterine bleeding. Guangming Journal Chinese Medicine[guang Ming Zhong Yi] 31, 1626–1628. [Google Scholar]
- Terai K., Horie S., Fukuhara S., Miyagawa Y., Kobayashi K., Tsujimura A. (2020). Combination therapy with antioxidants improves total motile sperm counts: a Preliminary Study. Reproductive Med. Biol. 19, 89–94. 10.1002/rmb2.12308 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tokumasu K., Matsuki N., Otsuka Y., Sakamoto Y., Ueda K., Matsuda Y., et al. (2025). Course of general fatigue in patients with Post-COVID-19 conditions who were prescribed hochuekkito: a single-center exploratory pilot Study. J. Clin. Med. 14, 1391. 10.3390/jcm14041391 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tricco A. C., Lillie E., Zarin W., O’Brien K. K., Colquhoun H., Levac D., et al. (2018). PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann. Intern Med. 169, 467–473. 10.7326/M18-0850 [DOI] [PubMed] [Google Scholar]
- Wang S. C. (2016). Clinical observation of Buzhong Yiqi method in the treatment of distention and fullness of sinking of qi due to deficiency of the spleen type. Chin. Community Doctors [zhong Guo She Qu Yi Shi] 32 (102), 104. [Google Scholar]
- Wang Y., Zhang Y., Liu Z., Li Q., Jin H. (2021). Effects of Buzhong Yiqi decoction combined with THP bladder perfusion on postoperative efficacy in patients with bladder cancer. Evidence-based complementary Altern. Med. 2021, 3685213–3685216. 10.1155/2021/3685213 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang J., Cheng C. W., Jiao Y., Shi D., Wang Y., Li H., et al. (2024). Evaluation of compliance of CONSORT-CHM formula 2017 in randomized controlled trials of Chinese herbal medicine formulas: protocol of a five-year review. Front. Pharmacol. 15, 1287262. 10.3389/fphar.2024.1287262 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watanabe M., Maeda J. (2022). Effects of Hochuekkito on physical activity and appetite in postoperative elderly patients with hip fractures: a randomized controlled trial. Prog. Rehabil. Med. 7, 20220063. 10.2490/prm.20220063 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wu J., Lu B., Yang D. D., Wu C., Wang H., Wang Z. Y. (2017). Flora regulation of buzhongyiqi decoction in patients with food allergies after surgery for anal fistula. Int. J. Clin. Exp. Med. 10, 6029–6041. [Google Scholar]
- Xu X.R., Zhou Y., Chen G., Lei M., Zhang W., Wu X. X., et al. (2023). Clinical efficacy of Buzhong Yiqi decoction in the treatment of hospital-acquired pneumonia with multi-drug resistant bacteria: a prospective, randomized, multicenter controlled trial. Journal of Traditional Chinese Medicine 43, 1010–1018. 10.19852/j.cnki.jtcm.20230713.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang H. Y. (2016). Clinical observation effect of mosapride combined with traditional Chinese medicine Buzhong Yiqi pill in the treatment of senile reflux esophagitis. Chin. Community Doctors, 32, 120–121. [Google Scholar]
- Zedler P., BüNTZEL J., Kuchta K., Yamaoka D., Sato N., Watanabe K., et al. (2024). Traditional clinical symptoms and signs: kampo pattern diagnosis in modern gastrointestinal disease. Front. Pharmacol. 15 1426491. 10.3389/fphar.2024.1426491 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhang A. J., Zhu Z. C. (2015). Taking Buzhong Yiqi Decoction associated with applying cervix to repair wound surface after loop electrosurgical excision procedure for 30 cases. Chin. Medicine Modern Distance Education china 13, 36–37. [Google Scholar]
- Zhong Y. Q., Fu J. J., Liu X. M., Diao X., Mao B., Fan T., et al. (2010). The reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of traditional Chinese medicine compound formulations and the differences between Chinese and Non-Chinese trials. Curr. Ther. Res. Clin. Exp. 71, 30–49. 10.1016/j.curtheres.2010.02.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhou F., Chen C., Shi J., Zhou Q., Jin L., Ma X. (2022). Clinical Study on the treatment of female stress urinary Incontinence with modified Buzhong Yiqi decoction. Front. Surg. 9, 882621. 10.3389/fsurg.2022.882621 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.