Dataset Information

Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide.

ABSTRACT: In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still unclear. To explore this, we collected pre- and post-treatment serum samples of 85 FC patients from MZRW/Senna/placebo treatment groups for pharmacometabolomic analysis. An ultrahigh-performance liquid chromatography-mass spectrometer (UPLC-MS) was used for metabolic profiling and quantification. In vivo studies were conducted in constipated C57BL/6J mice to verify the effects and corresponding mechanism(s) of the action of MZRW. Pearson correlation analysis, paired t-test, one-way ANOVA analysis, ?2 test, and Student t-test were used to interpret the clinical and preclinical data. Changes in levels of circulating oleamide and its derivatives negatively correlate with improvement in complete spontaneous bowel movement (CSBM) in the MZRW group (Pearson r = -0.59, p = 0.00057). The same did not hold true for either Senna or placebo groups. Oleamide is a known regulator of intestinal motility. MZRW treatment resulted in reduced levels of circulating oleamide in FC patients. Experimental verification showed that MZRW attenuated oleamide-induced slow intestinal motility in mice. MZRW decreased oleamide levels in serum, ileum, and colon in normal mice, but increased expression of colonic fatty acid amide hydrolase (FAAH). In conclusion, MZRW improved bowel movement in FC by down-regulating oleamide, possibly by enhancing FAAH-mediated degradation. Our findings suggest a novel therapeutic strategy for FC.

SUBMITTER: Huang T

PROVIDER: S-EPMC6989537 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide.

Huang Tao T Zhao Ling L Lin Cheng-Yuan CY Lu Lin L Ning Zi-Wan ZW Hu Dong-Dong DD Zhong Linda L D LLD Yang Zhi-Jun ZJ Bian Zhao-Xiang ZX

Frontiers in pharmacology 20200123

In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still uncle ...[more]

PMID: 32038247

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Project description:The goal of the study was to analyze whether WJP can alleviate visceral hypersensitivity in IBS-D model rats. In this study, 36 Sprague-Dawley (SD) rats aged 4 weeks old were randomly divided into two groups: the model group (n = 27) and the control group (n = 9). The rat model of IBS-D was established by modified compound methods for 4 weeks. After the modification, IBS-D rats were randomly divided into three groups, namely, the IBS-D model group (n = 9), the positive drug group (n = 9), and the WJP group (n = 9), with different interventions, respectively. The control group was fed and allowed to drink water routinely. The Bristol stool scale scores were used to assess the severity of diarrhea. Abdominal withdrawal reflex (AWR) scores were used to assess visceral sensitivity. Expression of TNF-α was measured, and histopathological examinations were performed to assess colon inflammation in IBS-D model rats. Key factors of the MEK/ERK signal pathway in the tissue of the colon and hippocampus were measured to analyze the mechanism of WJP. Compared with the control group, the Bristol stool scale scores in the model group were significantly increased (p < 0.0001). The scores of the WJP group were significantly decreased compared with the model group (p = 0.0001). Compared with the control group, AWR scores in the model group at each pressure level were significantly increased (p = 0.0003, p < 0.0001, p = 0.0007, and p = 0.0009). AWR scores of the WJP group were significantly decreased compared with the model group (p = 0.0003, p = 0.0007, p = 0.0007, and p = 0.0009). Compared with the control group, the model group had significantly higher expression of TNF-α in the colon tissue (p < 0.0001). However, the WJP group had significantly lower level of TNF-α compared with the model group (p < 0.0001). Meanwhile, compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue was significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the colon tissue were significantly decreased in the WJP group (p < 0.0001, p = 0.0019, and p = 0.0013). Compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue were significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the hippocampus tissue were significantly decreased in the WJP group (p = 0.0126, p = 0.0291, and p = 0.0145). The results indicated that WJP can alleviate visceral hypersensitivity in IBS-D model rats, possibly mediated by downregulating the expression of TNF-α, p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue. At the same time, WJP also affects downregulating the expression of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue.

Project description:PurposeTo comprehensively evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine (CHM) in treating irritable bowel syndrome with diarrhea (IBS-D).MethodsRelevant randomized controlled trials (RCTs) were systemically retrieved from electronic databases from inception to March 2018, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biological Medical Database (CBM, SinoMed), China Science and Technology Journal Database (VIP), and Wan Fang Data. Meanwhile, pooled estimates, including the 95% confidence interval (CI), were calculated for primary and secondary outcomes of IBS-D patients. Besides, quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool, and the Review Manager 5.3 and Stata12.0 softwares were employed for analyses.ResultsA total of 21 RCTs related to IBS-D were included into this meta-analysis. Specifically, the pooled results indicated that (1) acupuncture combined with CHM might result in more favorable improvements compared with the control group (relative risk [RR] 1.29; 95% CI 1.24-1.35; P =0.03); (2) the combined method could markedly enhance the clinical efficacy in the meantime of remarkably reducing the scores of abdominal pain (standardized mean difference [SMD] -0.45; 95% CI -0.72, -0.17; P = 0.002), abdominal distention/discomfort (SMD -0.36; 95% CI -0.71, -0.01; P = 0.04), diarrhea (SMD -0.97; 95% CI -1.18, -0.75; P < 0.00001), diet condition (SMD -0.73; 95% CI -0.93, -0.52; P<0.00001), physical strength (SMD -1.25; 95% CI -2.32, -0.19; P = 0.02), and sleep quality (SMD -1.02; 95% CI -1.26, -0.77; P < 0.00001) compared with those in the matched groups treated with western medicine, or western medicine combined with CHM. Additionally, a metaregression analysis was constructed according to the name of prescription, acupuncture type, treatment course and publication year, and subgroup analyses stratified based on the names of prescriptions and acupoints location were also carried out, so as to explore the potential heterogeneities; and (3) IBS-D patients treated with the combined method only developed inconspicuous adverse events; more importantly, the combined treatment had displayed promising long-term efficacy.ConclusionsFindings in this study indicate that acupuncture combined with CHM is suggestive of an effective and safe treatment approach for IBS-D patients, which may serve as a promising method to treat IBS-D in practical application. However, more large-scale, multicenter, long-term, and high-quality RCTs are required in the future, given the small size, low quality, and high risk of the studies identified in this meta-analysis.

Dataset Information

Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide.

Publications

Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide.

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