Zhizhu decoction alleviates slow transit constipation by regulating aryl hydrocarbon receptor through gut microbiota

Abstract

Context Slow transit constipation (STC), the most common type of constipation, seriously affects the life of patients. Zhizhu decoction (ZZD), a traditional Chinese medicine compound, has is effective against functional constipation, but the mechanism is still unclear. Objective This research explores the mechanism of ZZD on STC from the perspective of metabolomics and gut microbiota. Materials and methods Fifty-four C57BL/6 mice were randomly divided into six groups ( n = 9): control (control); STC (model); positive control (positive); low-dose (5 g/kg; L-ZZD), medium-dose (10 g/kg; M-ZZD), and high-dose (20 g/kg; H-ZZD) ZZD treatment. Following treatment of mice with ZZD for two weeks, the changes in intestinal motility, colon histology, intestinal neurotransmitters, and aryl hydrocarbon receptor (AHR) pathway determined the effects of ZZD on the pathophysiology of STC. LC-MS targeting serum metabolomics was used to analyze the regulation of ZZD on neurotransmitters, and 16S rRNA high-throughput sequencing was used to detect the regulation of the gut microbiome. Results ZZD had the highest content of naringin (6348.1 mg/L), and could significantly increase the 24 h defecations (1.10- to 1.42-fold), fecal moisture (1.14-fold) and intestinal transport rate (1.28-fold) of STC mice, increased the thickness of the mucosal and muscular tissue (1.18- to 2.16-fold) and regulated the neurotransmitters in the colon of STC mice. Moreover, ZZD significantly activated the AHR signaling pathway, and also affected the composition of gut microbiota in STC mice. Discussion and conclusions The beneficial effect and the possible mechanism of ZZD on STC could provide a theoretical basis for the broader clinical application of ZZD.

Mechanism of Mulberry Leaves and Black Sesame in Alleviating Slow Transit Constipation Revealed by Multi-Omics Analysis

“…The pathogenesis of STC is intricate, with intestinal motility deficiency identified as a key pathological mechanism. Intestinal motility includes various physiological aspects, including contractile movement of the intestinal muscles, sensitivity of the intestinal wall, biomechanical function of the intestinal tract, and colon injury [22]. Our findings suggest a potential role for SH in mitigating constipation-induced colonic injury.…”

Yunpi Tongbian Fang alleviates slow transit constipation induced by loperamide by regulating intestinal microbiota and short-chain fatty acids in rats

“…STC is a disease characterized by delayed colonic transport, 24-hour fecal volume, and fecal water content, and ITR can be used as a representative diagnostic indicator (10). This study found that after the intervention, the fecal water content, intestinal transport function, and pathological damage to the colon mucosa of STC rats were restored, with the high-dose group having the most significant improvement effect.…”

Considering traditional Chinese medicine as adjunct therapy in the management of chronic constipation by regulating intestinal flora

“…A Zhizhu decoction, consisting of Citrus aurantium (Zhi-Shi in Chinese) and Rhizoma Atractylodis Macrocephalae (Bai-Zhu in Chinese), is widely used in the treatment of functional gastrointestinal diseases caused by a spleen deficiency and Qi stagnation syndrome. The Zhizhu decoction has been reported to have beneficial laxative action on constipation in mouse models, which may be attributed to its ability to alter the composition of intestinal flora and activate the aryl hydrocarbon receptor (AHR) signaling pathway (76). In addition, the Zhizhu decoction increases the expression of Ach, SP, and 5-HT in the colon while decreasing the expression of VIP.…”