Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation.
Meiling Zheng, Rui Zhang, Huilin Liu, Xiaodi Guo, Qi Shao, Jing Zhang, Long Li, Jin Wang, Shan Miao, Xiaopeng Shi, Shanbo Ma
{"title":"Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation.","authors":"Meiling Zheng, Rui Zhang, Huilin Liu, Xiaodi Guo, Qi Shao, Jing Zhang, Long Li, Jin Wang, Shan Miao, Xiaopeng Shi, Shanbo Ma","doi":"10.1016/j.jep.2025.119696","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>SiniSan (SNS), a traditional formula from the Treatise on Typhoid Fever, has been shown in modern clinical practice to effectively treat both ulcerative colitis (UC) and depression, although the underlying mechanisms remain incompletely understood.</p><p><strong>Aim of the study: </strong>This study employed UPLC-Q-Orbitrap-MS, network pharmacology, molecular docking, and experimental validation to investigate SNS's mechanism in treating UC with comorbid depression.</p><p><strong>Materials and methods: </strong>UPLC-Q-Orbitrap-MS, in conjunction with network pharmacology and molecular docking, identified active constituents and potential targets of SNS. A UC model induced by a 3% dextran sulfate sodium (DSS) solution was used for experimental validation. Therapeutic efficacy was assessed through behavioral tests, ELISA, routine blood tests, histopathology, immunofluorescence, Western blot, and qRT-PCR.</p><p><strong>Results: </strong>SNS alleviated weight loss and inflammation in DSS-induced colitis in mice while exhibiting antidepressant effects in the open field test, forced swim test, and tail suspension test. Furthermore, SNS improved intestinal mucosal barrier function and restored hippocampal blood-brain barrier integrity. It inhibited microglial proliferation and neuroinflammation in the Hippocampus Cornu Ammonis 1 and dentate gyrus regions. Mechanistic analysis revealed that SNS mediates its effects on UC by modulating targets in the PI3K/AKT signaling pathway.</p><p><strong>Conclusions: </strong>SNS ameliorates UC with comorbid depression by restoring the integrity of both the intestinal mucosal barrier and the blood-brain barrier, alleviating DSS-induced colitis and neuroinflammation.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119696"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.119696","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: SiniSan (SNS), a traditional formula from the Treatise on Typhoid Fever, has been shown in modern clinical practice to effectively treat both ulcerative colitis (UC) and depression, although the underlying mechanisms remain incompletely understood.
Aim of the study: This study employed UPLC-Q-Orbitrap-MS, network pharmacology, molecular docking, and experimental validation to investigate SNS's mechanism in treating UC with comorbid depression.
Materials and methods: UPLC-Q-Orbitrap-MS, in conjunction with network pharmacology and molecular docking, identified active constituents and potential targets of SNS. A UC model induced by a 3% dextran sulfate sodium (DSS) solution was used for experimental validation. Therapeutic efficacy was assessed through behavioral tests, ELISA, routine blood tests, histopathology, immunofluorescence, Western blot, and qRT-PCR.
Results: SNS alleviated weight loss and inflammation in DSS-induced colitis in mice while exhibiting antidepressant effects in the open field test, forced swim test, and tail suspension test. Furthermore, SNS improved intestinal mucosal barrier function and restored hippocampal blood-brain barrier integrity. It inhibited microglial proliferation and neuroinflammation in the Hippocampus Cornu Ammonis 1 and dentate gyrus regions. Mechanistic analysis revealed that SNS mediates its effects on UC by modulating targets in the PI3K/AKT signaling pathway.
Conclusions: SNS ameliorates UC with comorbid depression by restoring the integrity of both the intestinal mucosal barrier and the blood-brain barrier, alleviating DSS-induced colitis and neuroinflammation.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
