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广藿香醇基于BMP-Smad信号通路治疗腹泻型肠易激综合征的机制

The mechanism of patchouli alcohol in treating IBS-D based on BMP-Smad pathway.

作者信息

Lu Yu-Lin, Huang Chen, Huang Shu-Yan, Li Ting, Chen Wan-Yu, Yi Shu-Lin, Pei Ying, Lu Jin-Tong, Chen Zhuo-Ying, Cao Hong-Ying, Tan Bo

机构信息

Research Centre of Basic Intergrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Biomed Pharmacother. 2025 Jun;187:118050. doi: 10.1016/j.biopha.2025.118050. Epub 2025 Apr 22.

Abstract

Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal condition, and diarrhea predominant (IBS-D) is the most common subtype.The enteric nervous system (ENS) regulates major gastrointestinal motility and function, and the intestinal neuronal BMP-SMAD signaling pathway is closely related to intestinal motility. Patchouli alcohol (PA) has been reported to modulate IBS-D, but whether its mechanism of action ameliorates IBS-D through the BMP-SMAD signaling pathway is unclear.This study preliminarily confirmed the abnormal colonic contraction of IBS-D functional bowel disease, and PA can not only improve gastrointestinal motor function, effectively inhibit the characteristic diarrhea and increased visceral sensitivity in IBS-D rats, but also regulate the neurohomeostasis of the gastrointestinal tract. In this study, in vivo and ex vivo studies confirmed that the neurohomeostatic regulation of patchouli alcohol was related to the increase of BMPRII neuronal subsets in the intestinal myenteric plexus and the regulation of BMP-SMAD signal pathway; PA increased the phosphorylation level of BMP-SMAD pathway-related proteins in IBS-D rat intestinal neurons.The findings can provide evidence for subsequent clinical research and drug development.

摘要

肠易激综合征(IBS)是一种慢性胃肠道疾病,腹泻型(IBS-D)是最常见的亚型。肠神经系统(ENS)调节主要的胃肠蠕动和功能,肠道神经元BMP-SMAD信号通路与肠道蠕动密切相关。据报道,广藿香醇(PA)可调节IBS-D,但尚不清楚其作用机制是否通过BMP-SMAD信号通路改善IBS-D。本研究初步证实了IBS-D功能性肠病的结肠收缩异常,PA不仅可以改善胃肠运动功能,有效抑制IBS-D大鼠的特征性腹泻和内脏敏感性增加,还可以调节胃肠道的神经内环境稳定。在本研究中,体内和体外研究证实,广藿香醇的神经内环境稳定调节与肠肌间神经丛中BMPRII神经元亚群的增加和BMP-SMAD信号通路的调节有关;PA增加了IBS-D大鼠肠道神经元中BMP-SMAD通路相关蛋白的磷酸化水平。这些发现可为后续的临床研究和药物开发提供证据。

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