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, c2 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.

A pilot randomized placebo-controlled study on modified MaZiRenWan: a formulated Chinese medicine to relieve constipation for palliative cancer patients

“…Our group has studied the pharmacology of MZRW and identified five representative active components, which can enhance colonic motility [ 21 ]. MZRW treatment in our previous study resulted in reduced levels of circulating oleamide, which is a known regulator of intestinal motility [ 22 ]. Further pharmacometabolomic analysis of MZRW for opioid-induced constipation can be explored when implementing a large-scale clinical trial in future.…”

Xuanhuang Runtong Tablets Relieve Slow Transit Constipation in Mice by Regulating TLR5/IL‐17A Signaling Mediated by Gut Microbes

“…Xuanhuang Runtong tablets (XHRTs) is a prescription composed of 9 Chinese herbal medicines, including Rehmannia glutinosa Libosch, Scrophulariae radix, Angelicae sinensis radix, Persicae semen, Cistanches herba, Cannabis fructus, Cassiae semen, and Aurantii fructus immaturus. The laxative effect of these Chinese herbal medicines has long been reported in the literature [ 11 – 14 ]. XHRT has a positive curative effect on functional constipation caused by yin deficiency, blood stasis, and senile functional constipation with reasonable safety and few side effects.…”

Effects of Compound Chinese Herbal Medicine Additive on Growth Performance and Gut Microbiota Diversity of Zi Goose

“…Gut microbiota is an important indicator of animal health. It was found that Chinese herb medicine mixture could up-regulate the abundance of beneficial flora in the broiler intestine ( Lactobacillus and Candida ), enhance intestinal immune mechanisms and accelerate intestinal motility [ 15 , 16 ]. In this experiment, CCHMA was added to the feed in a reasonable combination of seven herbs to improve the structure of the cecum flora, thereby improving the quality of animal products and ultimately achieving higher economic benefits.…”