Tongxie Anchang Decoction Relieves Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats by Regulating the NGF/TrkA Signaling Pathway

Abstract

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.

Major depressive disorder and irritable bowel syndrome risk: A Mendelian randomization study

“…These alterations can subsequently impact visceral sensation, intestinal movement, and endocrine function. Thus, this cascade of events may contribute to the onset or exacerbation of IBS symptoms [ 26 ].…”

Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry

“…A potential mechanism might explain MDD may lead to higher IBS risk. Drossman et al, found by functional magnetic resonance imaging that depression can activate the cingulate region of the limbic system of the cerebral cortex (Drossman et al, 2003); and the emotional activity center of the limbic system is in the same anatomical site as the vegetative center and the endocrine regulatory center, which govern the movement and secretion of the digestive tract; thus, the function of the vegetative center and the endocrine regulatory center is altered, and then the information is transmitted to the enteric nervous system through the brain-gut axis, causing changes in neurotransmitters and adrenocorticotropin-releasing factors, which affect visceral sensation, intestinal movement and endocrine function (Tan et al, 2021). In addition, study has shown that depression can lead to increased levels of expression of cytokines such as IL-1 β and TNF- α in the peripheral serum of patients (Miller, Maletic, & Raison, 2009).…”

Irritable bowel syndrome: Epidemiology, overlap disorders, pathophysiology and treatment

“…Furthermore, 60 IBS patients were enrolling in a study and were divided into the control group ( n = 20) and the treatment group ( n = 40), which were given oral pinaverium bromide tablets and Tongxie Yaofang decoction on the basis of conventional treatment, respectively. And the results reported that the flavored Tongxie Yaofang had a significant effect on the symptoms of patients with IBS-D[ 117 ], and improving the gut microbiome, alleviating visceral hypersensitivity, regulating 5-HT level in patients, and inhibiting colonic contraction are mechanisms for the treatment of IBS[ 118 - 120 ]. Moreover, Tongxie Anchang Decoction improves IBS by reducing visceral hypersensitivity, reversing mast cell infiltration, and regulating 5-HT[ 118 , 121 ].…”

“…And the results reported that the flavored Tongxie Yaofang had a significant effect on the symptoms of patients with IBS-D[ 117 ], and improving the gut microbiome, alleviating visceral hypersensitivity, regulating 5-HT level in patients, and inhibiting colonic contraction are mechanisms for the treatment of IBS[ 118 - 120 ]. Moreover, Tongxie Anchang Decoction improves IBS by reducing visceral hypersensitivity, reversing mast cell infiltration, and regulating 5-HT[ 118 , 121 ]. And Xiang Sha Liu Jun Zi Decoction reduced the mean diarrhea score of IBS patients[ 122 ].…”