ABSTRACT
Background and Aims
Chronic wounds, characterized by complex pathogenesis, prolonged healing duration, and high disability rates, pose significant therapeutic challenges. While accumulating evidence suggests that Traditional Chinese Medicine (TCM) exhibits unique advantages in managing this condition, a comprehensive systematic evaluation of its efficacy and safety remains lacking. This study aims to critically assess the therapeutic effects and adverse event profiles of TCM interventions for chronic wounds.
Methods
A systematic review and meta‐analysis of international online databases was conducted following PRISMA guidelines. PubMed, Embase, the Cochrane Library, OVID‐Medline, and the China National Knowledge Infrastructure (CNKI) database were searched using appropriate keywords from January 2013 to June 2024. RevMan 5.4 software recommended by the Cochrane Collaboration was used for meta‐analysis, was analyzed and the heterogeneity of statistical results using statamp‐64.
Results
The analysis incorporated 128 observational studies involving 9833 participants. TCM interventions demonstrated superior outcomes compared to controls across multiple endpoints: (1) Significant reduction in TCM syndrome scores (SMD = −0.84, 95% CI: −1.05 to −0.63; p < 0.00001); (2) Markedly lower visual analog scale (VAS) pain scores (SMD = −1.90, 95% CI: −2.53 to −1.27; p < 0.00001); (3) Favorable safety profile with reduced adverse reaction (RR = 0.43, 95% CI: 0.22‐0.88; p = 0.02; I² = 50%); (4) Enhanced clinical efficacy through improved total effectiveness rate (RR = 1.23, 95% CI: 1.19‐1.27; p < 0.00001) and recovery rate (RR = 2.01, 95% CI: 1.88‐2.14; p < 0.0001); (5) Accelerated wound healing evidenced by decreased wound area (SMD = −2.21, 95% CI: −2.65 to −1.76; p < 0.00001) and shortened healing time (SMD = −1.93, 95% CI: −2.22 to −1.64; p < 0.00001).
Conclusion
Our meta‐analysis demonstrates that TCM‐based therapies not only effectively alleviate clinical symptoms and improve quality of life but also accelerate wound repair in chronic wound patients without severe adverse reactions.
Keywords: chronic wound, Meta‐analysis, Traditional Chinese Medicine
1. Introduction
Chronic wounds, clinically defined as injuries failing to progress through sequential healing phases within 1 month, represent a therapeutic dilemma attributed to multifactorial pathogenesis involving vascular insufficiency, metabolic dysregulation, and microbial colonization [1]. This heterogeneous entity encompasses diabetic foot ulcers, pressure injuries, venous leg ulcers, and trauma‐related ulcers [2], collectively imposing substantial socioeconomic burdens due to prolonged treatment duration, frequent recurrences, and disability‐associated productivity losses [3]. Despite advancements in understanding the pathological mechanisms of chronic wounds, particularly the dysregulation of the inflammatory microenvironment and cellular senescence in wound beds [4], conventional western medicine therapies, such as surgical debridement, antimicrobials, and advanced dressings, have achieved unsatisfactory outcomes. These treatments face emerging challenges from biofilm persistence and antibiotic resistance [5].
In contrast to Western medical paradigms, Traditional Chinese Medicine (TCM) conceptualizes chronic wounds as “sores, stubborn sores, rotten legs” and other diseases. TCM has unique advantages and better therapeutic effects in the treatment of chronic skin ulcers [4]. Accumulating preclinical evidence highlights TCM's advantage in stimulating the formation of new blood vessels [5], improving blood circulation, activating the repair ability of the body [6], and regulating the synthesis and secretion of growth factors [7]. These advantages have drawn increasing attention from researchers and have made TCM an important means for the treatment of chronic skin ulcers. TCM employs stage‐specific symptom management and combines whole‐body treatment with local external treatment, which can accelerate wound healing, reduce scar formation, and improve the quality of wound healing [8]. Some external Chinese medicines or combined oral administrations have been proven effective in promoting the healing of diabetic foot ulcers feet, pressure sores, and lower limb vascular wounds. However, there is a lack of strict and effective evidence‐based medical evidence [9, 10, 11].
To address this issue, we screened research on the treatment of chronic wounds by external use or combined oral use of TCM over the past decade. This includes randomized controlled trials on common chronic wounds such as diabetic feet, pressure ulcers, and lower limb vascular wounds. We used Cytoscape to summarize the frequency and weight of monotherapeutic herbs in each disease. This study establishes a theoretical foundation for subsequent research on the application of TCM in the treatment of chronic wounds, offering a comprehensive framework for future investigations in this field. The present meta‐analysis evaluates the safety and efficacy of TCM in chronic wound management, aiming to substantiate its therapeutic potential and reinforce the evidence base for its clinical application.
2. Methods
This study performed a systematic review and meta‐analysis following PRISMA guidelines, spanning January 1, 2013 to June 11, 2024, to evaluate the therapeutic efficacy and safety profile of TCM in chronic wound management.
2.1. Inclusion Criteria
The following criteria were applied in selecting the studies: (1) research design: randomized controlled trial (RCT). (2) demographic: Chronic wounds, including diabetic foot ulcer, venous leg ulcer, and pressure sores. (3) intervention: TCM treatment or TCM combined with other methods of treatment.
2.2. Exclusion Criteria
Publications in the form of reviews, letters to the editor, and animal or cellular studies were excluded. In addition, retrospective studies and studies that were not original, papers reporting the same RCTs were all excluded.
2.3. Search Strategy
Online databases including PUBMED, EMBASE and COCHRANE, OVID‐Medline, China National Knowledge Infrastructure (CNKI) database, and Wanfang database were comprehensively searched. Relevant works were potentially eligible for screening irrespective of language and publication type from January 1, 2013 to October 27, 2022. The retrieval record on Pubmed is: (((“Medicine, Chinese Traditional”[Mesh]) OR (((((((((traditional Chinese medicine[Title/Abstract]) OR (Chinese herb[Title/Abstract])) OR (herbal medicine[Title/Abstract])) OR (Chinese medicine[Title/Abstract])) OR (Herbal Medicine[Title/Abstract])) OR (Medicinal herb[Title/Abstract])) OR (traditional oriental medicine[Title/Abstract])) OR (Chinese herbal medicine[Title/Abstract])) OR (Chinese medicinal herb[Title/Abstract]))) AND ((“Wounds and Injuries”[Mesh]) OR (((((((wound[Title/Abstract]) OR (diabetic foot ulcer[Title/Abstract])) OR (arterial ulcer[Title/Abstract])) OR (venous ulcer[Title/Abstract])) OR (varicose ulcer[Title/Abstract])) OR (pressure ulcer[Title/Abstract])))) AND ((“Randomized Controlled Trials as Topic”[Mesh]) OR ((((randomized controlled trial[Title/Abstract]) OR (controlled clinical trial[Title/Abstract])) OR (Randomized[Title/Abstract])) OR (controlled trial[Title/Abstract]))). At the same time, a manual search was conducted to supplement the literature, covering the period from October 27, 2022 to June 11, 2024.
2.4. Study Selection
Xia Hao and Dongzhen Zhu, both researchers on our scientific research team, independently screened the title and abstract of relevant research. In cases of discrepancies in study selection, they were promptly discussed or, when necessary, the third team researcher, Yang Wei, made the final selection. Studies were excluded if they had incorrect interventions (no TCM use), inappropriate participants, flawed study designs (non‐randomized or retrospective), or lacked meaningful results. Duplicates or secondary analyses of included randomized controlled trials were also removed (Figure 1). Finally, Tingting Liu, the fourth researcher, used Excel to compile information from the selected literature, including publication year, first author, sample size, intervention measures for b.
Figure 1.
PRISMA diagram illustrating the literature search, and study selection/exclusion process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐analyses; RCT, randomized controlled trials.
oth groups, participant characteristics, and treatment duration. In addition, primary and secondary outcomes were extracted from all included randomized controlled trials. As with the selection process, any discrepancies during data extraction were resolved through discussion. The outcome indicators extracted from the literature were: the TCM syndrome score, visual analogue scale (VAS) score, total effective rate, recovery rate, wound area, wound healing time, and adverse reactions.
2.5. Data Extraction and Management
Three researchers, Xia Hao, Dongzhen Zhu, and Wei Yang, independently extracted the following data: study characteristics, methodology of RCT, intervention plan, and control plan. Disagreements were resolved through discussions with reference sources.
2.6. Data Analysis
RevMan 5.4 software recommended by Cochrane Collaboration was used for meta‐analysis. SMD (Standardized Mean Difference) analysis is used for the measurement data, and RR (risk ratio) is used for the binary variable data. The above studies are all expressed with 95% confidence interval (CI). Meanwhile, the Cochrane Q test (p = 0.1 is the test level) is used for the assessment of heterogeneity, and I2 is used to reflect its heterogeneity. When I2 ≥ 50% or p < 0.1, it indicates substantial heterogeneity exists, and the random effect model is used to describe it. At this time, the fixed effect model is used to describe it and the publication bias is evaluated by funnel chart. At the same time, we analyzed the heterogeneity of statistical results using Stata/MP 64‐bit. If I2 ≥ 50% or p < 0.1, significant heterogeneity was considered present, and the random‐effects model was used. If I2 < 50% and p ≥ 0.1, heterogeneity was considered low, and the fixed‐effects model was applied with funnel plot assessment for publication bias. The heterogeneity of the statistical results was analyzed using Stata/MP‐64.
3. Results
3.1. Study Selection and Characteristics
The basic characteristics of the 128 included studies are summarized in Table 1 (supporting materials). These studies were conducted from 2013 to 2024, with 123 carried out in China and published in Chinese journals, and 5 in international journals. A total of 9,833 patients were enrolled, with sample sizes ranging from 26 to 440. All trials evaluated the effects of TCM combined with conventional therapy in chronic wound patients, with treatment lasting 1 to 6 months. Among them, 7 studies reported the TCM syndrome score, 104 the total effective rate, 88 the recovery rate, 10 the VAS scores, 39 the wound area, 34 the wound healing time, and only 4 studies mentioned adverse reactions. Using the Cochrane Risk of Bias Tool, no significant risk of bias was detected, and funnel plots showed no evidence of publication bias (Figure 2).
Figure 2.
Risk assessment of bias in randomized controlled trial (RCT):A. Risk of bias graph: Authors' percentage assessments of each risk of bias item across all studies. Overall quality: green—low risk of bias, yellow—unclear risk of bias, and red—high risk of bias. B. Summary of bias assessment: Authors' evaluations of each bias factor for each paper included.
3.2. The TCM Improve Patient's Syndrome and Life Quality
3.2.1. The TCM Syndrome Score
Among the included studies, seven articles reported data related to the TCM syndrome score. After conducting heterogeneity tests and sensitivity analyses, two studies (Shen Sijing 2018; Yao Zouying 2023) were identified as having a significant impact on heterogeneity and were excluded. The remaining five articles demonstrated low heterogeneity (χ² = 5.86, p = 0.21, I² = 32%). Therefore, the fixed‐effect model was used for meta‐analysis (Figure 3). The results indicated that TCM interventions showed significantly better outcomes than the control group in reducing the TCM syndrome score (SMD = −0.84; 95% CI: −1.05 to −0.63; p < 0.00001), suggesting that TCM treatment can significantly improve the symptoms of chronic wounds.
Figure 3.
Forest plot showing SMD (with 95% CI) for the the TCM syndrome score studies comparing TCM with control in a fixed‐effect model.
3.2.2. Visual Analogue Scale Score
A total of 10 studies with 40 cases compared VAS scores for chronic wounds between TCM and control treatments. Significant statistical heterogeneity was found (p < 0.00001; I² = 93%), and the funnel plot showed asymmetry, suggesting possible publication bias (Figure S1). Thus, the random‐effect model was used for meta‐analysis (Figure 4), which showed that the TCM group had a much lower VAS score than the control group (SMD = −1.90; 95% CI: −2.53 to −1.27; p < 0.00001).
Figure 4.
Forest plot showing SMD (with 95% CI) for the the Visual Analogue Scale score studies comparing TCM with control in a random‐effect model.
To explore heterogeneity reasons, regression analysis was done on publication year, disease classification, and treatment methods, none of which caused heterogeneity (p = 0.957, 0.859, 0.697). Due to limited literature, subgroup analysis wasn't conducted. Egger's test found significant publication bias (p = 0.006), which was corrected by the pruning method, with no result reversal before and after pruning.
Before pruning, there was significant heterogeneity (Q = 133.944, p < 0.001), so the random‐effects model was used (p < 0.001). After including one virtual study's data and re‐conducting meta‐analysis, the results were still heterogeneous (Q = 169.872, p < 0.001). Using the random‐effects model (p < 0.001), the combined effect indicator was IOR = 0.129, 95% CI: 0.067‐0.246. The results were not statistically significant and no reversals occurred, so combined results were credible (Figure S2–S4).
3.3. The TCM Accelerates Wound Healing
3.3.1. The Total Effective Rate
A total of 104 articles reported the relevant data of clinical total effective rate, covering 7769 patients (3906 in the test group and 3863 in the control group). Given the significantly high heterogeneity (I² = 77%, p < 0.00001), the random‐effects model was applied for meta‐analysis (Figure 5). The results demonstrated that TCM treatment can remarkably enhance the total effective rate of chronic wound healing (RR = 1.23; 95% CI: 1.19‐1.27; p < 0.00001).
Figure 5.
Forest plot showing RR (with 95% CI) for the total effective rate studies comparing TCM with control in a random‐effect model.
Regression analysis was performed on publication year, disease classification, and treatment methods to explore heterogeneity causes. None of these three covariates were found responsible for heterogeneity (p = 0.641, 0.849, 0.139). The funnel plot's asymmetry indicated potential publication bias (Figure S5), which was also detected by Egger's test (p < 0.001) and later corrected using the pruning method. Results remained stable with no reversals before and after pruning (Q = 479.318, p < 0.001), indicating robustness and reliability despite existing heterogeneity that didn't affect the overall result (Figure S6–S8).
3.3.2. The Recovery Rate
Among the included studies, 88 reported on the recovery rate. After excluding one article (Yu Mingying 2016) that significantly impacted heterogeneity through individual study exclusion and sensitivity analysis, 87 articles were ultimately included. These articles involved a total of 6887 patients, with 3572 in the test group and 3315 in the control group. The studies showed homogeneity (χ² = 156.94, p < 0.00001, I² = 45%), so a fixed‐effects model was used for statistical analysis. Results indicated that TCM can significantly improve the recovery rate of chronic wounds (RR = 2.01; 95% CI: 1.88‐2.14; p < 0.0001) (Figure 6).
Figure 6.
Forest plot showing RR (with 95% CI) for the recovery rate studies comparing TCM with control in a fixed‐effects model.
3.3.3. The Wound Area
Thirty‐nine studies reported data on the wound area of chronic wounds, covering 2778 patients (1393 in the test group and 1385 in the control group). Given the significantly high heterogeneity (I² = 96%, p < 0.00001), the random‐effect model was used for meta‐analysis (Figure 7). Results showed that TCM treatment can significantly reduce wound area (SMD = −2.21, 95% CI: −2.65 to −1.76, p < 0.00001).
Figure 7.
Forest plot showing SMD (with 95% CI) for the wound area studies comparing TCM with control in a random‐effect model.
The funnel plot's asymmetry indicated potential publication bias (Figure S9). Regression analysis on publication year, disease classification, and treatment method found none of these covariates caused heterogeneity (p = 0.846, 0.176, 0.364). Egger's test detected significant publication bias (p < 0.001), which was corrected by the trim and fill method. There was no result reversal before and after pruning (Q = 907.138, p < 0.001, using the random‐effects model, p < 0.001), The combined effect indicators were IOR = 0.078, 95% CI: 0.046‐0.133. Results were not statistically significant and no reversals occurred, so the combined results were credible (Figure S10–S12).
3.3.4. The Wound Healing Time
Thirty‐four studies evaluated the impact of TCM on chronic wound healing time, encompassing 1167 patients in the TCM group and 1139 in the control group. Due to significant heterogeneity (I² = 87%, p < 0.00001), a random‐effects model was employed for meta‐analysis (Figure 8). Results showed that TCM could markedly shorten wound healing time (SMD = −1.93; 95% CI: −2.22 to −1.64; p < 0.00001).
Figure 8.
Forest plot showing SMD (with 95% CI) for the wound healing time studies comparing TCM with control in a random‐effect model.
The funnel plot's asymmetry pointed to possible publication bias (Figure S13). Regression analysis on publication year, disease classification, treatment method, and Treatment duration found that none of these four covariates were the cause of heterogeneity (Figure S14). Egger's test detected significant publication bias (p = 0.001), which was corrected by the trim‐and‐fill analysis (Figure 9, 10).
Figure 9.
Eggers publication bias results (there was a significant publication bias on the results of different studies). CI, confidence interval.
Figure 10.
Trim and Fill Analysis, the dots represent studies, the dots enclosed in the box represent the “shadow data” that was inserted after the Trim and Fill. CI, confidence interval.
Results remained stable with no reversals before and after pruning (Q = 248.386, p < 0.001, using the random‐effects model, p < 0.001). After incorporating data from five virtual studies, meta‐analysis results were still heterogeneous (Q = 489.676, p < 0.001). The combined effect indicators were IOR = 0.098, 95% CI: 0.070‐0.138. Results were not statistically significant and no reversals occurred, so combined results were credible.
3.3.5. Adverse Reactions
Four studies assessed the adverse reactions of TCM in chronic wound patients, revealing a significantly lower incidence in the TCM group (RR = 0.43, 95% CI: 0.22‐ 0.88, p = 0.02, I² = 50%). The I² value indicates acceptable heterogeneity in the statistical results, so the random‐effects model was applied for meta‐analysis (Figure 11).
Figure 11.
Forest plot showing RR (with 95% CI) for the adverse reactions studies comparing TCM with control in a random‐effect model.
3.4. Cytoscape Software: Analysis of the Composition of TCM for Diseases
To properly investigate the potential mechanism of TCM in treating chronic wounds and provide physicians with more referential prescription formulas, Cytoscape software was employed to identify common ingredients across diverse prescriptions. Based on the degree of importance determined by the Cytoscape MCODE plugin, the central square in the generated network represents different prescriptions, while the surrounding circles represent different single TCM ingredients. The color gradient, ranging from yellow to dark green to purple, reflects the degree value of each node. The top 5 TCM ingredients are highlighted in the innermost first circle (Figure 12).
Figure 12.
Formula‐ingredient network for lower limb venous ulcer treatment. Square nodes (labeled D/P/L+number) denote different therapeutic formulas of diabetic wound, pressure ulcer and lower limb venous ulcer, respectively; colors range from yellow to purple, where darker shades signify higher weights. Elliptical nodes represent ingredients, with higher weights characterized by darker colors, larger font sizes, and positions closer to the network center.
In this meta‐analysis, apart from five articles on single TCM ingredients, the remaining included articles focused on TCM prescriptions. Most of the TCM prescriptions are custom‐formulated, but there are also some classic prescriptions, such as Buyang Huanwu Decoction, Buzhong Yiqi Decoction, and Simiao Yong'an Decoction. The dosage forms involved include ointment, decoction, powder, oral formulations, injection, semi‐fluid dosage form, and paste. The compositions of these prescriptions were summarized in Table 2 (supporting materials). MCODE plugin was used to identify key modules within the network while CytoHubba is used to filter the interaction network and select core ingredients.
4. Discussion
This systematic review and meta‐analysis was conducted to evaluate the therapeutic efficacy and safety of TCM in chronic wound management, with a focus on diabetic foot ulcers, venous leg ulcers, and pressure injuries. To our knowledge, this represents the first comprehensive synthesis of evidence comparing TCM interventions with conventional therapies across seven clinical endpoints: TCM syndrome score, total effective rate, the recovery rate, VAS score wound, the wound area, wound healing time, and the adverse reactions. This meta‐analysis includes a total of 128 clinical studies.
Notably, 80% of TCM interventions involved topical applications (lotions and plasters, powders, oils), while 20% utilized oral formulations (decoctions, proprietary Chinese medicines). Therapeutic protocols are predominantly derived from classical formulae with modifications, administered via localized wound irrigation/compression or oral delivery. We found that TCM, either alone or in combination with other treatments, was associated with a significant improvements therapeutic outcomes in the of chronic wounds.
In our meta‐analysis, heterogeneity was indicated by an I² value greater than 50%. Our statistical results showed no heterogeneity in adverse reactions, but heterogeneity was present in other indicators. Heterogeneity was assessed using a stepwise exclusion method. Through this approach, studies contributing to heterogeneity in TCM syndrome scores and recovery rates were systematically identified and removed, reducing the overall heterogeneity to below 50% and thereby confirming the reliability of the results. For the remaining four indicators the VAS score, total effective rate, wound area, and wound healing time‐heterogeneity could not be resolved by individually screening the literature. Therefore, we employed regression analysis, trim and fill method, and other verification methods. The results indicated that heterogeneity did not influence the final conclusions.
4.1. Discussion on Key Indicators
The TCM syndrome score and VAS can partially reflect the quality of life of patients with chronic wounds. The TCM syndrome score evaluates wound pain, color, pus odor, thirst level, and limb numbness/itching on a 0‐6‐point scale. Lower scores indicate milder symptoms and better recovery [12]. The VAS, a common pain assessment tool, allows clinicians and investigators to document pain progression in patients during wound healing studies and serves as a key indicator of treatment efficacy [13]. Both the TCM syndrome score and VAS showed significant improvements compared to the control group. Notably, TCM's pain‐relieving effects have garnered significant attention from scholars in the field, with many Chinese medicines used in prescriptions reported to have analgesic properties. For instance, compound Phellodendron solution is effective for post‐operative mixed hemorrhoid edema and pain [14], while Danggui Sini Decoction and its modified versions can treat dysmenorrhea‐related pain [15], and Danggui Shaoyao Powder, which promotes blood circulation and removes blood stasis, can also treat dysmenorrhea [16].
Clinical efficacy, recovery rate, wound area, and wound healing time are all important indicators for evaluating chronic wound outcomes. Multidimensional assessment of chronic wound management in this meta‐analysis consistently showed TCM's therapeutic advantages over conventional approaches.
The evaluation of drug side effects is of great significance for ensuring patient safety, optimizing treatment plan and promoting rational drug use. Studies showed a lower incidence of adverse reactions in the TCM group compared to the conventional group. It proved that Chinese medicine does have the advantages of less adverse reactions and more safety. However, due to small sample sizes and a lack of standardized adverse reaction reporting in some studies, there is still clinical heterogeneity in the current evidence. The safety characteristics of TCM need further verification through large‐scale, multi‐center clinical studies.
Furthermore, some indicators are less discussed in the literature, but they are of great significance to guide the clinical treatment of chronic wounds. Firstly, nerve conduction velocity is slowed down due to the destruction of peripheral nerve nutrition, demyelination, and axonal degeneration in diabetic foot patients. This aligns with the concept of blood stasis and collateral obstruction in traditional Chinese medicine. Zhang et al. found that TCM treatment improved motor and sensory nerve conduction velocities in the common peroneal and sural nerves, suggesting that combined TCM interventions can repair damaged nerves, enhance nerve tissue transmission, and promote diabetic recovery [17]. Secondly, bFGF and VEGF, widely distributed in the body, drive angiogenesis, granulation tissue growth, scar formation, and tissue regeneration. In diabetic patients, ischemia leads to declining bFGF and VEGF levels, reducing tissue regeneration and delaying wound healing. Research shows TCM can enhance bFGF and VEGF expression in rats with focal tissue ischemia. Increased bFGF in diabetic foot tissue boosts tissue repair growth factor receptor activity, promoting cell proliferation, granulation tissue growth, and local anti‐infection and nutrition. VEGF promotes endothelial cell proliferation and migration via paracrine effects, forming new capillaries, stimulating angiogenesis and granulation tissue growth, and improving the local nutritional status to facilitate wound repair and diabetes control [18, 19, 20, 21, 22, 23, 24]. In the future, TCM research on chronic wounds should include these indicator measurements to better evaluate therapeutic effects and explore mechanisms.
4.2. Bioinformatics Analysis
TCM's complex components and mechanisms pose challenges for understanding its clinical effects. To provide evidence for TCM's clinical application, we used Cytoscape to visually analyze the weight of single herbs in chronic wound treatment. This approach is significant for revealing the synergistic mechanisms of multi‐component and multi‐target TCM compounds.
High‐weight drugs are usually the core components of the compound, which may play a role by regulating more targets or key pathways, reflecting the compatibility of traditional Chinese medicine. It may exert a comprehensive curative effect through the characteristics of “one drug and multiple targets”. In our analysis, considering software parameters and the medicinal value of the analyzed herbs, the top five single TCMs were identified (Figure 12). They are Danggui, huangqi, huangbai, honghua, and chuanxiong. Danggui has the function of promoting blood circulation and removing blood stasis [25]. Modern pharmacological studies have found that danggui has the effects of anticoagulation, anti‐inflammatory, antioxidant, analgesic, and immune enhancement [26]. Its anti‐inflammatory component is angelica polysaccharide [27], with ferulic acid as an active ingredient that reduces blood viscosity, inhibits platelet aggregation [28], and has antidiabetic and antioxidant properties, accelerating wound healing and skin regeneration [29, 30]. Large‐dose intravenous or intravenous drip of danggui liquid can treat thrombosis and occlusive vasculitis, relieve limb pain, promote blood circulation, improve skin temperature, prevent necrosis, and promote wound healing [31, 32]. Huangqi has the effect of tonifying the middle and replenishing qi, expelling pus, and promoting tissue regeneration [33]. Studies have demonstrated that it enhances immunity, promotes protein and DNA synthesis, regulates energy metabolism and immune function, exhibits anti‐inflammatory effects, modulates angiogenesis, and reduces tissue fibrosis [34, 35, 36, 37]. Saponins, flavonoids, and trace elements in huangqi can activate various pathways, such as nuclear factor‐κB (NF‐κB), tyrosine kinase (JAK1), phosphatidylinositol 3‐kinase (PI3K), protein kinase B (Akt), vascular endothelial cell growth factor receptor (VEGFR2), etc [38, 39, 40]., all of which are conducive to the division and proliferation of fibroblasts, vascular endothelial cells, epidermal cells in the wound surface [41]. Huangbai has the effect of clearing away heat, drying dampness, purging fire, removing steam, detoxifying and curing sores [42]. Modern research confirms anti‐inflammatory, immunosuppressive, anti‐tumor, anti‐ulcer, hypoglycemic, and neuroprotective effects, with good results for skin dampness and sores [43]. It contains a variety of alkaloids, such as berberine, which has the effect of anti‐pathogenic microorganisms, such as inhibiting Staphylococcus aureus and some skin fungi [44]. In addition, it can down‐regulate the expression of IL‐6, MMP‐9, etc. by inhibiting the NF‐kB signal pathway, thus playing the role of anti‐inflammatory and promoting wound healing [45]. Honghua can promote blood circulation, remove blood stasis, and relieve pain [46]. Chuanxiong promotes blood circulation and qi, dispels wind, and relieves pain, it contains a variety of chemical components, such as ligustrazine, sodium ferulate, ligusticum chuanxiong lactone etc [47]. Ligustrazine, the main active component, dilates microvessels, lowers blood viscosity, regulates platelet function, prevents thrombosis, eliminates oxygen free radicals, improves tissue collagen metabolism, accelerates hematoma absorption, promotes scab formation, and inhibits multiple bacteria [48]. Analyzing the weight of each herb in TCM prescriptions via Cytoscape transforms the TCM experience into quantifiable network parameters. This provides a basis for understanding compound mechanisms, optimizing treatment plans, and advancing TCM modernization. This multidisciplinary method is ideal for studying complex diseases like chronic wounds.
4.3. Limitations
This study included 128 RCTs with a relatively large sample size, yielding relatively reliable conclusions. However, the research design has limitations: Firstly, the randomization method and allocation scheme were imperfect. Secondly, most of the included studies lacked blinding methods. In addition, most TCM researchers tend to focus on empirical medicine, which leads to the lack of rigorous experimental design and mixed experimental data. These issues indicate a need for further standardization in this field. Our results require further verification through large‐scale, double‐blind, and other standardized studies.
5. Conclusion and Prospect
This meta‐analysis demonstrates that TCM significantly improves chronic wound outcomes, including reductions in TCM syndrome scores (SMD = −0.84), pain (VAS: SMD = −1.90), wound area (SMD = −2.21), and healing time (SMD = −1.93), while enhancing total effectiveness (RR = 1.23) and recovery rates (RR = 2.01) versus conventional treatments (p < 0.00001 for all). TCM also exhibited fewer adverse reactions (RR = 0.43). Bioinformatics identified Danggui, Huangqi, Huangbai, Honghua, and Chuanxiong as core herbs, likely acting via anti‐inflammatory, angiogenic, and tissue‐repair mechanisms. Despite heterogeneity in some outcomes, robustness was confirmed through sensitivity analyses. These findings advocate for TCM's integration into chronic wound management, though further high‐quality RCTs are needed to standardize protocols.
While TCM's multi‐component formulations achieve therapeutic effects through herbal compatibility, their complexity poses mechanistic interpretation challenges. Deciphering individual components' contributions and compound formulation mechanisms requires integration with bioinformatics and molecular target analysis. This interdisciplinary approach is crucial for advancing TCM's global acceptance in chronic ulcer treatment.
Author Contributions
Xia Hao: writing – original draft, conceptualization, formal analysis. Dongzhen Zhu: conceptualization, writing – original draft, writing – review and editing. Jinbo Zhang: writing – review and editing. Tingting Liu: data curation, writing – review and editing. Zhimin Yao: data curation, writing – review and editing. Qingju Sun: writing – review and editing. Bin Yao: methodology, supervision, writing – review and editing. Wei Yang: data curation, writing – review and editing.
Conflicts of Interest
The authors declare no conflicts of interest.
Transparency Statement
The lead author Qingju Sun, Bin Yao affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Supporting information
Table 1: Basic characteristics of the included trials. Table 2: Components of Chinese herbal medicine used in the included trials.
Supplementary Information
Acknowledgments
This work was supported by Natural Science Foundation of Tianjin (Grant IDs: 21JCQNJC01070), National Key Research and Development Program of China (Grant IDs: 2022YFC2403100 and 2021YFF1200800), Shandong Province Natural Science Foundation Youth Project (Grant IDs: ZR2021QC085), Applied Basic Research Foundation of Tianjin (Grant IDs: 22JCQNJC00360, 22JCQNJC00980) and Tianjin Health Research Project (Grant IDs: TJWJ2023QN050), Tianjin Health Research Project (ZC20112). All authors have read and approved the final version of the manuscript Bin Yao had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.
Hao X., Zhu D., Zhang J., et al., “Efficacy and Safety of Chinese Herbal Medicine for Patients With Chronic Wound: A Systematic Review and Meta‐Analysis,” Health Science Reports 9 (2026): e71809. 10.1002/hsr2.71809.
The authors wish to state that, in their opinion, Xia Hao, Dongzhen Zhu, and Jinbo Zhang contributed equally to this work and should be regarded as joint first authors.
Contributor Information
Qingju Sun, Email: sunqingju@126.com.
Bin Yao, Email: hongyaobin_1212@tju.edu.cn.
Wei Yang, Email: yangyang_517@sina.com.
Data Availability Statement
Data available on request from the authors.
References
- 1. Falcone M., De Angelis B., Pea F., et al., “Challenges in the Management of Chronic Wound Infections,” Journal of Global Antimicrobial Resistance 26 (2021): 140–147. [DOI] [PubMed] [Google Scholar]
- 2. Jiang Y., Fu X., Lu S., Niu Y., Zhu J., “Tissue Repair and Regeneration Disorders: Repair and Regeneration of Chronic Refractory Wounds.” in Regenerative Medicine in China, eds. Fu X. (Springer Singapore, 2021), 139–178). [Google Scholar]
- 3. Las Heras K., Igartua M., Santos‐Vizcaino E., and Hernandez R. M., “Chronic Wounds: Current Status, Available Strategies and Emerging Therapeutic Solutions,” Journal of Controlled Release 328 (2020): 532–550. [DOI] [PubMed] [Google Scholar]
- 4. Dorai A. A., “Wound Care With Traditional, Complementary and Alternative Medicine,” Indian Journal of Plastic Surgery 45, no. 2 (2012): 418–424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Ai X., Yu P., Hou Y., et al., “A Review of Traditional Chinese Medicine on Treatment of Diabetic Retinopathy and Involved Mechanisms,” Biomedicine & Pharmacotherapy 132 (2020): 110852. [DOI] [PubMed] [Google Scholar]
- 6. Bu L., Dai O., Zhou F., et al., “Traditional Chinese Medicine Formulas, Extracts, and Compounds Promote Angiogenesis,” Biomedicine & Pharmacotherapy 132 (2020): 110855. [DOI] [PubMed] [Google Scholar]
- 7. Yazarlu O., Iranshahi M., Kashani H. R. K., et al., “Perspective on the Application of Medicinal Plants and Natural Products in Wound Healing: A Mechanistic Review,” Pharmacological Research 174 (2021): 105841. [DOI] [PubMed] [Google Scholar]
- 8. Que H. F., “Tcm Diagnosis and Treatment of Chronic Skin Ulcer,” Global Chinese Medicine 3, no. 02 (2010): 96–100. [Google Scholar]
- 9. Du L., Zeng D., Hu X., Ren X., and He D., “The Efficacy of Autologous Platelet‐Rich Gel and Traditional Chinese Medicine in Diabetic Foot Treatment: A Parallel Randomized Controlled Clinical Trial,” Annals of Vascular Surgery 87 (2022): 529–537. [DOI] [PubMed] [Google Scholar]
- 10. Liu J., Cai M., Yan H., et al., “Yunnan Baiyao Reduces Hospital‐Acquired Pressure Ulcers via Suppressing Virulence Gene Expression and Biofilm Formation of Staphylococcus Aureus,” International Journal of Medical Sciences 16, no. 8 (2019): 1078–1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Lu X., Xu Q., Li P., and Zhang Z., “Therapeutic Effect of a Traditional Chinese Medicine on the Treatment of Painful Leg Ulcer,” International Journal of Lower Extremity Wounds 19, no. 1 (2020): 89–98. [DOI] [PubMed] [Google Scholar]
- 12. Li B. Clinical Study on the Treatment of Venous Ulcer of Lower Extremities With Venous No. 1, 2020. Shanxi University of Traditional Chinese Medicine.
- 13. Garmi G., Parasol M., Zafran N., Rudin M., Romano S., and Salim R., “Efficacy of Single Wound Infiltration With Bupivacaine and Adrenaline During Cesarean Delivery for Reduction of Postoperative Pain: A Randomized Clinical Trial,” JAMA Network Open 5, no. 11 (2022): e2242203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Tang L. J., Yu H., and Y. Qixian., “Clinical Study of Compound Huangbai Liquid on Wound Healing After Perianal Abscess Surgery,” Chinese Journal of Clinical Pharmacology 37, no. 06 (2021): 668–670+689. [Google Scholar]
- 15. Ma C., Liang N., Gao L., and Jia C., “Danggui Sini Decoction (Herbal Medicine) for the Treatment of Primary Dysmenorrhoea: A Systematic Review and Meta‐Analysis,” Journal of Obstetrics and Gynaecology 41, no. 7 (2021): 1001–1009. [DOI] [PubMed] [Google Scholar]
- 16. Tzeng T. F., Liou S. S., and Liu I. M., “The Selected Traditional Chinese Medicinal Formulas for Treating Diabetic Nephropathy: Perspective of Modern Science,” Journal of Traditional and Complementary Medicine 3, no. 3 (2013): 152–158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Liu P., “Research Progress of Peripheral Substance P Involved in Diabetic Foot Wound Healing and Intervention of Traditional Chinese Medicine,” Chinese Journal of Integrated Traditional Chinese and Western Medicine Surgery 26, no. 06 (2020): 1206–1208. [Google Scholar]
- 18. Sha L. J., “Clinical Efficacy of Vacuum Sealing Drainage Combined With Traditional Chinese Medicine Application in the Treatment of Diabetic Foot Ulcer and Its Impact on Wound Healing, Angiogenesis Indicators, IGF‐1, Pedf,” Chinese Medicine Research 34, no. 12 (2021): 44–47. [Google Scholar]
- 19. Zhou W. X., “Effect of Tongluo Juyu Formula on Wound Healing and Vascular Endothelial Growth Factor in Elderly Patients With Type 2 Diabetic Foot Ulcer,” Guangming Traditional Chinese Medicine 36, no. 01 (2021): 90–92. [Google Scholar]
- 20. Ye Q. L., “Observation on the Efficacy of External Application of Traditional Chinese Medicine in the Treatment of Venous Ulcer of Lower Extremity,” Journal of Nurse Training 34, no. 07 (2019): 665–667. [Google Scholar]
- 21. Zhang B., “Effect of Mebo Combined With Fumigation and Washing of Traditional Chinese Medicine on Vegf, Crp and Ulcer Healing in Patients With Diabetic Foot,” Laboratory Medicine and Clinic 16, no. 23 (2019. [Google Scholar]
- 22. Bai X. H., “Effect of Traditional Chinese Medicine Fumigation Combined With Conventional Western Medicine Treatment on Diabetic Foot Ulcer Healing and Vegf, MMP‐2 and TIMP‐1 in Wound Exudate,” Journal of Traditional Chinese Medicine 59, no. 20 (2018. [Google Scholar]
- 23. Wang G., “Clinical Observation on Treating 100 Cases of Leg Sores With Traditional Chinese Medicine Ulcer Oil,” Chinese Journal of Basic Chinese Medicine 22, no. 04 (2016. [Google Scholar]
- 24. Zhang H., “Clinical Study on 59 Cases of Diabetic Foot Treated With Comprehensive Therapy of Traditional Chinese Medicine,” Chinese Journal of Experimental Formulary 21, no. 14 (2015): 161–164. [Google Scholar]
- 25. Huang Y., Ni N., Hong Y., Lin X., Feng Y., and Shen L., “Progress in Traditional Chinese Medicine for the Treatment of Migraine,” American Journal of Chinese Medicine 48, no. 8 (2020): 1731–1748. [DOI] [PubMed] [Google Scholar]
- 26. Sarker S. and Nahar L., “Natural Medicine: The Genus Angelica,” Current Medicinal Chemistry 11, no. 11 (2004): 1479–1500. [DOI] [PubMed] [Google Scholar]
- 27. Nai J., Zhang C., Shao H., et al., “Extraction, Structure, Pharmacological Activities and Drug Carrier Applications of Angelica Sinensis Polysaccharide,” International Journal of Biological Macromolecules 183 (2021): 2337–2353. [DOI] [PubMed] [Google Scholar]
- 28. Li D., Rui Y., Guo S., Luan F., Liu R., and Zeng N., “Ferulic Acid: A Review of Its Pharmacology, Pharmacokinetics and Derivatives,” Life Sciences 284 (2021): 119921. [DOI] [PubMed] [Google Scholar]
- 29. Xu X., Zhu T., Shi T., Chen J., and Jin L., “Quality Suitability Regionalization Analysis of Angelica Sinensis in Gansu, China,” PLoS One 15, no. 12 (2020): e0243750. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Anand S., Pandey P., Begum M. Y., et al., “Electrospun Biomimetic Multifunctional Nanofibers Loaded With Ferulic Acid for Enhanced Antimicrobial and Wound‐Healing Activities in Stz‐Induced Diabetic Rats,” Pharmaceuticals 15, no. 3 (2022): 302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Chen X. P., Li W., Xiao X. F., Zhang L. L., and Liu C. X., “Phytochemical and Pharmacological Studies on Radix Angelica Sinensis,” Chinese Journal of Natural Medicines 11, no. 6 (2013): 577–587. [DOI] [PubMed] [Google Scholar]
- 32. Hu Y., Lei S., Yan Z., et al., “Angelica Dahurica Regulated the Polarization of Macrophages and Accelerated Wound Healing in Diabetes: A Network Pharmacology Study and In Vivo Experimental Validation,” Frontiers in Pharmacology 12 (2021): 678713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Aamar E., Avigad Laron E., Asaad W., Harshuk‐Shabso S., and Enshell‐Seijffers D., “Hair‐Follicle Mesenchymal Stem Cell Activity During Homeostasis and Wound Healing,” Journal of Investigative Dermatology 141, no. 12 (2021): 2797–2807.e6.e6. [DOI] [PubMed] [Google Scholar]
- 34. Tan Y. Q., Chen H. W., and Li J., “Astragaloside Iv: An Effective Drug for the Treatment of Cardiovascular Diseases,” Drug Design, Development and Therapy 14 (2020): 3731–3746. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Yu W. N., Sun L. F., and Yang H., “Inhibitory Effects of Astragaloside Iv on Bleomycin‐Induced Pulmonary Fibrosis in Rats via Attenuation of Oxidative Stress and Inflammation,” Inflammation 39, no. 5 (2016): 1835–1841. [DOI] [PubMed] [Google Scholar]
- 36. Zhang Z., Wang J., Zhu Y., Zhang H., and Wang H., “Astragaloside Iv Alleviates Myocardial Damage Induced by Type 2 Diabetes via Improving Energy Metabolism,” Molecular Medicine Reports 20, no. 5 (2019): 4612–4622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Lu W., Zhang Y., Liu D., Songyang Z., and Wan M., “Telomeres‐Structure, Function, and Regulation,” Experimental Cell Research 319, no. 2 (2013): 133–141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Sheik A., Kim K., Varaprasad G. L., et al., “The Anti‐Cancerous Activity of Adaptogenic Herb Astragalus Membranaceus,” Phytomedicine 91 (2021): 153698. [DOI] [PubMed] [Google Scholar]
- 39. Chen Z., Liu L., Gao C., et al., “Astragali Radix (Huangqi): A Promising Edible Immunomodulatory Herbal Medicine,” Journal of Ethnopharmacology 258 (2020): 112895. [DOI] [PubMed] [Google Scholar]
- 40. Seto S. W., Chang D., Jenkins A., Bensoussan A., and Kiat H., “Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine,” Journal of Clinical Medicine 5, no. 6 (2016): 56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. He W., Chen P., Chen Q., Cai Z., and Zhang P., “Cytokine Storm: Behind the Scenes of the Collateral Circulation After Acute Myocardial Infarction,” Inflammation Research 71, no. 10–11 (2022): 1143–1158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Tang L., Huang L., and Lai Y., “Network Pharmacology and Bioinformatics Analyses Identify the Intersection Genes and Mechanism of Huang Bai for Recurrent Aphthous Stomatitis,” International Journal of Immunopathology and Pharmacology 36 (2022): 3946320221129134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Sun Y., Lenon G. B., and Yang A. W. H., “Phellodendri Cortex: A Phytochemical, Pharmacological, and Pharmacokinetic Review,” Evidence‐Based Complementary and Alternative Medicine 2019 (2019): 1–45. [Google Scholar]
- 44. Calvo A., Moreno E., Aldalur I., et al., “Effect of Topical Berberine in Murine Cutaneous Leishmaniasis Lesions,” Journal of Antimicrobial Chemotherapy 77, no. 4 (2022): 1072–1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Chen Y., Xian Y., Lai Z., Loo S., Chan W. Y., and Lin Z. X., “Anti‐Inflammatory and Anti‐Allergic Effects and Underlying Mechanisms of Huang‐Lian‐Jie‐Du Extract: Implication for Atopic Dermatitis Treatment,” Journal of Ethnopharmacology 185 (2016): 41–52. [DOI] [PubMed] [Google Scholar]
- 46. Zhai J., Ji Z., Jin X., Du X., Cao L., and Zheng W., “Meta‐Analysis of the Effect of Honghua Injection in the Treatment of Coronary Heart Disease Angina Pectoris,” Evidence‐Based Complementary and Alternative Medicine 2022 (2022): 1–11. [Google Scholar]
- 47. Huang S., Chen J., Liu X., et al., “Evaluation of the Pharmaceutical Activities of Chuanxiong, a Key Medicinal Material in Traditional Chinese Medicine,” Pharmaceuticals 17, no. 9 (2024): 1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48. Lin J., Wang Q., Zhou S., Xu S., and Yao K., “Tetramethylpyrazine: A Review on Its Mechanisms and Functions,” Biomedicine & Pharmacotherapy 150 (2022): 113005. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table 1: Basic characteristics of the included trials. Table 2: Components of Chinese herbal medicine used in the included trials.
Supplementary Information
Data Availability Statement
Data available on request from the authors.