Abstract
OBJECTIVE: To evaluate the effectiveness and safety of Xiangsha Liujun pills (香砂六君丸) on the decreased digestive function in patients in the recovery phase of the Coronavirus disease 2019 (COVID-19).
METHODS: A randomized, double blind, placebo controlled clinical trial was conducted. A total of 200 COVID-19 patients in the recovery phase were included in our study in Ezhou Hospital of Traditional Chinese Medicine. Totally 200 subjects were randomly divided into a treatment group (Xiangsha Liujun pills) and a control group (placebo), with 100 in each group. Subjects took Xiangsha Liujun pills or placebo orally three times a day for two weeks. Three visits were scheduled at week 0 (baseline), week 1 (the middle of the intervention) and week 2 (the end of the intervention) for each eligible patient. The total efficacy rates for improving the Traditional Chinese Medicine (TCM) symptoms (fatigue, poor appetite, abdominal distension and loose stools) and the disappearance rates of symptoms were observed and compared in the treatment and control groups. Adverse events were recorded during the study period. SAS 9.4 was used to analyze the data.
RESULTS: A total of 200 patients were included in this study, among which 4 participants withdrew because the drugs did not work. Three patients were excluded for age. Before the treatment, there was no significant difference between the TCM symptoms scores of subjects. After 1 week of treatment, the full analysis set (FAS) showed that the efficacy rates for abdominal distension and loose stools in the treatment group were significantly higher than the control group (P < 0.05). There were no significant differences in the efficacy rates for fatigue and poor appetite between the two groups (P >0.05). In addition, the disappearance rate of fatigue in the treatment group was significantly higher than the control group (P <0.05); there were no significant differences between the two groups after treatment in the rates of poor appetite, abdominal distension, and loose stools (P>0.05). After 2 weeks of treatment, the efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the treatment group were significantly higher than the control group (P <0.05). The disappearance rate of loose stools in the treatment group was significantly higher than the control group (P < 0.05). However, there were no significant differences in the disappearance rates of fatigue, poor appetite, and abdominal distension between the two groups (P > 0.05). No severe adverse events were reported by subjects during the study.
CONCLUSIONS: This clinical study confirmed that Xiangsha Liujun pills can effectively improve the symptoms related to the decreased digestive function in COVID-19 convalescent patients.
Keywords: COVID-19, digestion, symptom complex, treatment outcome, safety, recovery phase, Xiangsha Liujun pills
1. INTRODUCTION
The Coronavirus Disease 2019 (COVID-19) is an acute respiratory illness and caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is a positive-strand RNA virus that can result in a severe respiratory syndrome in humans.1,2 As of August 9, 2022, more than 580 million persons were infected with COVID-19, and over 6 million people have died of COVID-19.3
In patients with COVID-19 infection, respiratory system symptoms have been confirmed as the most typical and significant manifestation, such as fever, cough.4,⇓-6 Apart from respiratory symptoms, more studies have shown that the symptoms of the digestive system have been found in the infected COVID-19 patients.5,⇓,⇓,⇓- 9 Guan et al 4 discovered that 3.8% of patients with COVID-19 have diarrhea from a study with 1099 laboratory-confirmed COVID-19 patients. Cheung et al 10 also found that diarrhea, nausea, vomiting, and abdominal pain or discomfort were the common symptoms presented in 4243 COVID-19 patients by a meta-analysis. In addition, most studies showed that diarrhea with a prevalence of 22.1% (95% CI: 19.6%-24.7%) in 1059 patients.11 Moreover, researchers have detected SARS-CoV-2 in stool samples from the infected patients.12 Enteric manifestations of SAR-CoV-2 not only show the diagnostic challenge to doctors when facing COVID-19 patients but also signify potential faecal transmission of this virus.
As we all know, Traditional Chinese Medicine (TCM) has achieved some success in the treatment of COVID-19. Some ancient TCM prescriptions, such as Lianhua Qingwen capsules/granules (连花清瘟胶囊/颗粒) and Jinhua Qinggan granules (金花清感颗粒), have been screened out for the treatment of COVID-19 based on their clinical symptoms by clinicians.13 Xiangsha Liujun pills (香砂六君丸) is based on Si Junzi Tang (六君子汤) with the supplementation of Chinese herbal medicine such as Banxia (Rhizoma Pinelliae), Chenpi (Pericarpium Citri Reticulatae), Muxiang (Radix Aucklandiae), and Sharen (Fructus Amomi). According to the concept of TCM, Xiangsha Liujun pills have the efficacy to regulate Qi-flowing for eliminating phlegm, strengthen the spleen and stomach, replenish Qi, and eliminate cold to relieve pain. In this study, we evaluated the therapeutic effect of Xiangsha Liujun pills to improve the clinical symptoms of decreased digestive function including fatigue, poor appetite, abdominal distension and loose stools in COVID-19 convalescent patients, providing the treatment ideas for COVID-19 patients with symptoms of the digestive system.
2. MATERIALS AND METHODS
2.1. Study design
This is a random, double blind, placebo control clinical trial. All patients were in Hubei Province and during the recovery phase of COVID-19 as defined in the 7th edition of the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia.14 In accordance with randomization, eligible patients were randomly assigned to the treatment group (Xiangsha Liujun pills) or a control group (placebo) in a 1 ∶1 ratio. Xiangsha Liujun pills or placebo was administered to each group for 2 weeks. Three visits were scheduled for each eligible patient: week 0 (baseline), week 1 (the middle of the intervention) and week 2 (the end of the intervention).
2.2. Ethics approval and consent to participate
The trial protocol was approved by the Medical Ethics Committee of Ezhou Hospital of Traditional Chinese Medicine (approval No. 2020-07). According to theories guiding the appropriate use of TCM in clinical applications, the study design followed the principles set out in the GCP guidelines. All the subjects should confirm and sign the informed consent forms, which mainly involved the possible risks, the purpose of the study and the procedures of the study. When the protocol required revision, the Ethics Committee of Ezhou Hospital of Traditional Chinese Medicine must be approved before the implementation. In this trial, trained research assistants or investigators introduced and discussed the research information to eligible patients who wanted to participate. All the participants who agreed to participate were required to sign an informed consent form. Participants may withdraw from the trial at any time.
2.3. Diagnostic criteria for the recovery phase of COVID-19
The diagnostic criteria were based on Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7).14
2.3.1 General suspected cases
A systemic analysis was performed combining the following epidemiological histories and clinical presentations:
Epidemiological history: (a) history of travel or residence in Wuhan or the surrounding area or other case-reporting communities within 14 d prior to the onset of illness; (b) history of contact within 14 d prior to the onset of illness with people infected with COVID-19 (positive by nucleic acid test); (c) contact within 14 d prior to the onset of illness with patients who had a fever or respiratory symptoms and were from Wuhan or the surrounding area or from case-reporting communities; (d) clustering in outbreak.
Clinical presentation: (a) fever and/or respiratory symptoms; (b) imaging features of COVID-19 as described above; (c) normal or decreased total white blood cell count and decreased lymphocyte count early in the disease course.
People with one of the epidemiological histories and two of the clinical manifestations and those with no definite epidemiological history but had all the clinical manifestations were regarded as general suspected cases.
2.3.2 Confirmed cases
Confirmed cases were suspected cases that also had one of the following etiologic attributes: (a) positive reverse transcription-polymerase chain reaction test for SARS-CoV-2; (b) viral gene sequencing showing high homology to known SARS-CoV-2; (c) the presence of serum SARS-CoV-2-specific IgM and IgG antibodies. Serum SARS-CoV-2-specific IgG antibody turning from negative to positive, or a 4-fold or greater increase in this IgG level in the recovery phase compared with the acute phase.
2.3.3 Discharge criteria for the recovery phase of COVID-19
(a) Body temperature returning to normal for more than 3 d. (b) Significantly improved respiratory symptoms. (c) Lung imaging showing significantly reduced inflammation. (d) Two consecutive nucleic acid tests from a sputum sample, a nasopharyngeal swab, or another respiratory specimen (sampling interval of at least 24 h) were negative. Patients could be discharged when all of the above conditions were met.
2.4. Inclusion criteria
Participants who met all of the following criteria were eligible: (a) Patients who met the diagnostic criteria for COVID-19 recovery phase. (b) Patients whose main clinical manifestations were symptoms of decreased digestive function (fatigue, poor appetite, abdominal distension and loose stools), or who had three of these symptoms at the same time, or who had a visual analog scale score higher than 4 for a single symptom. (c) Patients who were cured and discharged from the hospital more than 2 weeks prior. (d) Patients aged 18-70 years. (e) Patients who signed the informed consent form.
2.5. Exclusion criteria
(a) Patients who had difficulty oral drugs due to basic diseases and other reasons. (b) Patients who had the serious basic diseases affected survival, including uncontrolled heart, lung, kidney, digestion, blood disease, mental illness, immune disease, metabolic disease, malignant tumor, severe malnutrition, etc. (c) Allergic constitution or allergic to the ingredients of this drug. (d) Pregnancy or lactating women. (e) Patients who were not able to cooperate as well as could not clearly express themselves because of a psychiatric disorder. (f) Participated in other clinical trials.
2.6. Randomization and blinding
In our study, patients were given random numbers which were generated by a block of randomization sequences using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) in a 1∶1 ratio. Subjects were randomly divided into a treatment group and a control group, with 100 patients in each group. Experimental technicians, statisticians, project sponsors, data managers and outcome analysts all were blinded of the treatment allocations. To meet the requirements of the blind-trial method, the trial medicine and placebo were provided by the Zhongjing Wanxi Pharmaceutical Co., Ltd. (Xixia, China) (batch No. 200203). The main ingredient of placebo was glutinous rice starch and sugar. The auxiliary ingredient was activated carbon, and caramel pigment. A random number table generated from fixed numbers of seeds was provided by statisticians. During this study, the patients and researchers were also blinded.
2.7. Treatment plan
The patients in experimental group were given Xiangsha Liujun pills (eight pills were equivalent to 3 grams of the original medicine) with the following prescription: taking 12 pills orally, three times per day, 30 min before each meal. The treatment course was 2 weeks in duration.
Patients in the placebo group received placebo which was given as prescribed by a physician, taken orally, one packet per dose, three times per day, 30 min before each meal. The treatment course was 2 weeks in duration.
2.8. Observation indicators
2.8.1 Primary evaluation indicators
The primary efficacy indicators were the efficacy rates and disappearance rates of TCM symptoms (fatigue, poor appetite, abdominal distension and loose stools). The symptoms were scored using a visual analog scale at weeks 0, 1, and 2. The two ends of vernier calipers were set to “0” and “10”, with “0” indicating no symptoms and “10” indicating severe symptoms. Patients were instructed to move the vernier calipers to score their symptoms severity from 0 (no symptoms) to 10 (very severe), with higher scores indicating more severe. The highest score and the average score within 24 h were recorded.
2.8.2 Evaluation criteria for the efficacy
(a) Cured: all of the TCM symptoms and signs disappeared, and the TCM symptom score gone down to 0. (b) Significantly effective: TCM symptoms were significantly relieved. Signs disappear and the TCM symptom score was reduced by more than 70%. (c) Effective: TCM symptoms were beginning to be relieved. Signs started to disappear, and TCM symptom score was reduced by more than 30%. (d) Ineffective: no TCM symptoms or signs relieved, or even worsened, and the TCM symptom score was reduced by less than 30%.
The calculation formula is (Nimodipine method): [(total score before treatment - total score after treatment) ÷ total score before treatment] × 100%.
2.8.3 Evaluation of safety
To assess the safety of Xiangsha Liujun pills, the tests of heart rate and blood pressure in patients at the baseline and the end of the intervention periods were implemented.
2.9. Statistical analysis
The data analysis was conducted by professional bio-statisticians using standardized statistical methods. The full analysis set (FAS) was used in the efficacy analysis, and the safety set (SS) was used in the safety analysis. The statistical analyses were carried out using SAS 9.4 software (SAS Institute Inc., Cary, NC, USA). The measurement data were statistically described by case number, mean, standard deviation, median, maximum, and minimum and compared using the independent Student's t test or Wilcoxon's rank sum test. The count and ordinal data were expressed as the frequency and rate and compared using the χ2 or Fisher's exact test. P value<0.05 was considered statistically significant.
3. RESULTS
A total of 200 COVID-19 patients in the recovery phase were included in our study in Ezhou Hospital of Traditional Chinese Medicine. The study design and flow diagram of this study is demonstrated in Figure 1.
Figure 1. Study design and flow chart.
3.1. Baseline data
The FAS included 200 cases for statistical analysis, which were divided into treatment group and control group, 100 cases in each group. Before the treatment, there was no significant difference between the TCM symptoms scores of subjects by FAS analysis.
3.2. Comparison of the efficacy rates for TCM symptoms
The efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the two groups were compared by FAS analysis. After 1 week of treatment, in the treatment group, the efficacy rates for abdominal distension and loose stools were significantly higher than the control group (P<0.05). However, there were no significant differences in the efficacy rates for fatigue and poor appetite between the two groups (P>0.05) (Table 2).
Table 2.
Comparison of the efficacy rates of the TCM symptoms in the two groups
| TCM Symptom | Group | Treatment time |
Total number | Effective number | Ineffective number | Effective rate (%) |
Ineffective rate (%) |
P value |
|---|---|---|---|---|---|---|---|---|
| Fatigue | Treatment | 1 week | 80 | 48 | 32 | 60.00 | 40.00 | 0.174 |
| Control | 83 | 41 | 42 | 49.40 | 50.60 | |||
| Treatment | 2 weeks | 80 | 70 | 10 | 87.50 | 12.50 | 0.006a | |
| Control | 83 | 58 | 25 | 69.88 | 30.12 | |||
| Poor appetite | Treatment | 1 week | 75 | 48 | 27 | 64.00 | 36.00 | 0.408 |
| Control | 80 | 46 | 34 | 57.50 | 42.50 | |||
| Treatment | 2 weeks | 75 | 72 | 3 | 96.00 | 4.00 | <0.001a | |
| Control | 80 | 62 | 18 | 77.50 | 22.50 | |||
| Abdominal distension | Treatment | 1 week | 90 | 61 | 29 | 67.78 | 32.22 | 0.016a |
| Control | 88 | 44 | 44 | 50.00 | 50.00 | |||
| Treatment | 2 weeks | 90 | 81 | 9 | 90.00 | 10.00 | <0.001a | |
| Control | 88 | 52 | 36 | 59.09 | 40.91 | |||
| Loose stools | Treatment | 1 week | 40 | 29 | 11 | 72.50 | 27.50 | 0.001a |
| Control | 52 | 20 | 32 | 38.46 | 61.54 | |||
| Treatment | 2 weeks | 40 | 37 | 3 | 92.50 | 7.50 | <0.001a | |
| Control | 52 | 25 | 27 | 48.08 | 51.92 |
Notes: TCM: Traditional Chinese Medicine. P value: comparison between the treatment group and the control group. aP<0.05 indicates a significant difference.
Table 1.
TCM symptoms scores before the treatment
| TCM Symptom | Group | Mean | Min-Max | Median | Mean±SD | F value | P value |
|---|---|---|---|---|---|---|---|
| Fatigue | Treatment | 3 | 0-10 | 2 | 2.7±2.2 | 0.000 | 1.000 |
| Control | 3 | 0-7 | 3 | 2.7±1.9 | |||
| Poor appetite | Treatment | 3 | 0-9 | 3.5 | 2.8±2.2 | ﹣0.745 | 0.457 |
| Control | 3 | 0-7 | 4 | 3.0±2.0 | |||
| Abdominal distension | Treatment | 4 | 0-8 | 4 | 3.8±2.0 | ﹣0.754 | 0.451 |
| Control | 4 | 0-7 | 3 | 3.6±2.0 | |||
| Loose stools | Treatment | 2 | 0-9 | 0 | 1.6±2.3 | ﹣1.518 | 0.131 |
| Control | 2 | 0-7 | 0 | 2.1±2.5 |
Notes: TCM: Traditional Chinese Medicine; SD: standard deviation. P value: comparison between the treatment group and the control group.
After 2 weeks of treatment, the efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the treatment group were significantly higher than the control group (P<0.05) (Table 2).
3.3. Comparison of the disappearance rates of the TCM symptoms
The disappearance rates of fatigue, poor appetite, abdominal distension, and loose stools were compared by FAS analysis. After 1 week of treatment, the disappearance rate of fatigue in the treatment group was significantly higher than the control group (P<0.05); there were no significant differences between the two groups in the disappearance rates of poor appetite, abdominal distension, and loose stools (P>0.05) (Table 3).
Table 3.
Comparison of the disappearance rates of the TCM symptoms in the two groups
| TCM Symptom | Group | Treatment time |
Total number | Symptom disappear number | Symptom exist number | Symptom disappear rate (%) | Symptom exist rate (%) |
P value |
|---|---|---|---|---|---|---|---|---|
| Fatigue | Treatment | 1 week | 80 | 6 | 74 | 7.50 | 92.50 | 0.047a |
| Control | 83 | 1 | 82 | 1.20 | 98.80 | |||
| Treatment | 2 weeks | 80 | 26 | 54 | 32.50 | 67.50 | 0.867 | |
| Control | 83 | 28 | 55 | 33.73 | 66.27 | |||
| Poor appetite | Treatment | 1 week | 75 | 4 | 71 | 5.33 | 94.67 | 0.150 |
| Control | 80 | 1 | 79 | 1.25 | 98.75 | |||
| Treatment | 2 weeks | 75 | 32 | 43 | 42.67 | 57.33 | 0.736 | |
| Control | 80 | 32 | 48 | 40.00 | 60.00 | |||
| Abdominal distension | Treatment | 1 week | 90 | 8 | 82 | 8.89 | 91.11 | 0.761 |
| Control | 88 | 9 | 79 | 10.23 | 89.77 | |||
| Treatment | 2 weeks | 90 | 34 | 56 | 37.78 | 62.22 | 0.608 | |
| Control | 88 | 30 | 58 | 34.09 | 65.91 | |||
| Loose stools | Treatment | 1 week | 40 | 10 | 30 | 25.00 | 75.00 | 0.835 |
| Control | 52 | 14 | 38 | 26.92 | 73.08 | |||
| Treatment | 2 weeks | 40 | 25 | 15 | 62.50 | 37.50 | 0.022a | |
| Control | 52 | 20 | 32 | 38.46 | 61.54 |
Notes: TCM: Traditional Chinese Medicine. P value: comparison between the treatment group and the control group. aP<0.05 indicates a significant difference.
After treatment for 2 weeks, the disappearance rate of loose stools in the treatment group was significantly higher than the control group (P<0.05). However, there were no significant differences in the disappearance rates of fatigue, poor appetite, and abdominal distension between the two groups (P>0.05) (Table 3).
3.4. Comparison of the TCM symptoms scores after treatment
In treatment and control groups, those patients who scored 0 for fatigue, poor appetite, abdominal distension, and loose stools before treatment were not included in the statistical analysis. The number of patients who scored 0 for each symptom before treatment was as follows: fatigue, 37; poor appetite, 45; abdominal distension, 22; and loose stools, 108.
After 1 week of treatment, symptom scores for abdominal distension and loose stools in the treatment group were lower than the control group (P<0.001). However, there were no significant differences in the fatigue and poor appetite scores between the two groups (P>0.05) (Table 4).
Table 4.
Comparison of the TCM symptoms scores after treatment in the two groups
| TCM Symptom | Group | Treatment time |
Total number | Mean ± SD | F value | P value |
|---|---|---|---|---|---|---|
| Fatigue | Treatment | 1 week | 80 | 2.3±1.7 | 0.809 | 0.491 |
| Control | 83 | 2.4±1.5 | ||||
| Treatment | 2 weeks | 80 | 1.3±1.4 | 8.235 | <0.001a | |
| Control | 83 | 1.5±1.7 | ||||
| Poor appetite | Treatment | 1 week | 75 | 2.2±1.4 | 1.361 | 0.257 |
| Control | 80 | 2.5±1.3 | ||||
| Treatment | 2 weeks | 75 | 0.9±1.1 | 16.237 | <0.001a | |
| Control | 80 | 1.4±1.6 | ||||
| Abdominal distension | Treatment | 1 week | 90 | 2.6±1.5 | 12.486 | <0.001a |
| Control | 88 | 2.8±1.7 | ||||
| Treatment | 2 weeks | 90 | 1.3±1.5 | 43.933 | <0.001a | |
| Control | 88 | 2.2±2.1 | ||||
| Loose stools | Treatment | 1 week | 40 | 2.1±1.9 | 12.655 | <0.001a |
| Control | 52 | 3.2±2.6 | ||||
| Treatment | 2 weeks | 40 | 0.8±1.5 | 21.750 | <0.001a | |
| Control | 52 | 2.8±2.7 |
Notes: TCM: Traditional Chinese Medicine; SD: standard deviation. P value: comparison between the treatment group and the control group. aP<0.05 indicates a significant difference.
After 2 week of treatment, there was a statistically difference between the two groups in symptom scores for fatigue, poor appetite, abdominal distension, and loose stools (P<0.001) (Table 4).
3.5. Safety
Heart rate and blood pressure were taken as safety indexes. During the 2-week follow-up, there were no emerging heart rate abnormalities in the two groups. Compared with baseline, the number of systolic pressure abnormalities was 3 (3.00%) and the number of diastolic pressure abnormalities was 5 (5.00%) in the treatment group (Table 5). In the control group, 3 (3.00%) and 5.00 (5%) cases were found abnormal in systolic pressure and diastolic pressure, respectively. After χ2 test, the difference between the two groups was not statistically significant (P>0.05) (Table 5).
Table 5.
Comparison of emerging abnormalities in heart rate and blood pressure during the trial
| Treatment time | Group | Total number | Number of systolic pressure abnormalities | Number of diastolic pressure abnormalities | P value |
|---|---|---|---|---|---|
| 2 weeks | Treatment | 100 | 3 | 5 | 1.000 |
| Control | 100 | 3 | 5 | 1.000 |
Note: P value: comparison between the treatment group and the control group.
4. DISCUSSION
Many sufferers have recovered from COVID-19 by treatment with TCM. Observation of the symptoms of digestive system in the recovery phase can provide more information and guide the further treatment for the COVID-19 patients. In our study, 200 patients were included and divided into the treatment group and the control group. Both the Xiangsha Liujun pills (for the treatment group) and the placebo (for the control group) were topically applied thrice daily for two weeks.
Before the treatment, there was no significant difference between the TCM symptoms scores of subjects (P>0.05). After 1 week of treatment, the FAS showed that the efficacy rates for abdominal distension and loose stools in the treatment group were significantly higher than the control group (P<0.05). The disappearance rate of fatigue in the treatment group was significantly higher than the control group (P <0.05). After 2 weeks of treatment, the efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the treatment group were significantly higher than the control group (P<0.05). And the disappearance rate of loose stools in the treatment group was significantly higher than the control group (P<0.05). Meanwhile, no severe adverse events were reported during the study. As a result, Xiangsha Liujun pills can improve the decreased digestive function-related TCM symptoms in convalescent patients with COVID-19.
In fact, the symptoms of digestive system have been found commonly in the recovery phase of patients with COVID-19. On the other hand, COVID-19 has been classified as a “cold-dampness epidemic” disease in TCM theory.15 Xiangsha Liujun pills were used to treat digestive system diseases based on holistic treatment of TCM and symptom pattern. Therefore, this study mainly evaluated the efficacy and safety of Xiangsha Liujun pills in treating the decreased digestive function in the recovery phase of COVID-19 patients and provided a treatment idea about relieving clinical symptoms of digestive system by TCM treatment.
Our study showed that Xiangsha Liujun pills can improve the fatigue, poor appetite, abdominal distension, and loose stools in COVID-19 patients in the recovery phase after two weeks of treatment. Xiao et al 15 explained the mechanism of COVID-19 by TCM theory and discovered that the epidemic caused by cold-dampness toxin which might be trap the spleen and cause spleen-Yang stagnation contributing to some symptoms of digestive system, such as poor appetite, fatigue, nausea, abdominal distension, vomiting and loose stools. In this study, we found that the cold dampness can be cleared and the clinical symptoms can be improved by Xiangsha Liujun pills.
Previous pharmacology studies have confirmed that gastric empty can be accelerated and the motilin releasing can be enhanced by Muxiang decoction (木香煎剂).16 Animal studies have suggested that different doses of the Muxiang decoction can contribute to intestinal propulsion and gastric emptying.17,18 Modern pharmacology research found some active ingredients in Baizhu, such as glycosides, lactones, amino acids and polysaccharides.19 Furthermore, several studies discovered that Baizhu can enhance the activity of salivary amylase, promote the intestinal absorption and the intestinal flora status, stimulate the smooth muscle myoelectricity and contribute to the proliferation of Lactobacillus and Bifidobacterium.20,⇓-22 It has been found that Fuling can relax intestinal muscles and reduce contraction amplitude.23,24 Studies have noted that spontaneous contraction intestinal muscles can be reduced by Gancao with glycyrrhizin and glycyrrhetinic acid.25,26 Besides, a number of studies pointed that Chenpi can contribute to the activity of pepsin, the excretion of gastric juice, and improvement of digestive function.27,28 Finally, there are several limitations existed in this study. Due to the urgency and limitations of the time, the secondary efficacy indicator did not explicitly set, and the safety indicators were not enough, so in-depth and comprehensive research is required to carry out in future.
In conclusion, our study confirmed that Xiangsha Liujun pills can effectively improve the TCM symptoms of decreased digestive function in convalescent patients infected with COVID-19. Nevertheless, further investigation with larger sample size and more safety data still required for examination of the treatment efficacy and safety of Xiangsha Liujun pills.
5. ACKNOWLEDGMENTS
We thank the patients and researchers involved in this study.
Contributor Information
Xiaolin TONG, Email: tongxiaolin@vip.163.com.
Yuanming BA, Email: 1723426138@qq.com.
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