Qiaoxia Wang , Xiaoxuan Liu , Dongxing Song , Qingqing Wang , Mengjiao Wu , Zhihao Zhu , Mingxuan Jin , Siqi Liu , Jian Zhang , Rufeng Wang
{"title":"肠安颗粒通过调节脑肠轴5-羟色胺信号通路治疗腹泻型肠易激综合征的机制及有效成分探讨","authors":"Qiaoxia Wang , Xiaoxuan Liu , Dongxing Song , Qingqing Wang , Mengjiao Wu , Zhihao Zhu , Mingxuan Jin , Siqi Liu , Jian Zhang , Rufeng Wang","doi":"10.1016/j.phymed.2024.156350","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Changan Granule (CAG) is a drug product developed from a traditional Chinese medicine (TCM) empirical prescription for diarrhea-predominant irritable bowel syndrome (IBS-D). The action mechanism and effective compounds of CAG in the treatment of IBS-D are not well understood.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the effectiveness, action mechanism and effective compounds of CAG for treating IBS-D.</div></div><div><h3>Methods</h3><div>Network pharmacology was used to screen the related pathways and active compounds of CAG in the treatment of IBS-D. Neonatal mother-infant separation, acetic acid enema and colorectal dilation were employed to construct IBS-D model for <em>in vivo</em> study. The effectiveness of CAG was evaluated in accordance with the results of body weight measurement, fecal water content determination, abdominal withdraw reflex test, open field test, sucrose preference test, forced swimming test and hematoxylin-eosin (HE) staining. The protein and mRNA levels of key molecules regulated by CAG were assessed through enzyme-linked immunosorbent assay (ELISA), western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The active compounds from CAG screened by network pharmacology were investigated with Caco-2 and RIN-14B cell models <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Network pharmacological analysis showed that CAG regulated 5-hydroxytryptamine (5-HT) signaling pathway and tetrahydropalmatine, formononetin and corydaline might be the potential effective compounds. The validation experiments showed that CAG restored the decreased body weight, and alleviated intestinal sensitivity, low-grade inflammation, diarrhea, frequent defecation, anxiety and depression of IBS-D rats through regulating the expression levels of 5-HT, tryptophan hydroxylase (TPH)1/2, serotonin transporter (SERT), 5-hydroxytryptamine-3 and -4 receptors (5-HT<sub>3</sub>R and 5-HT<sub>4</sub>R) in brain-gut axis (BGA). Tetrahydropalmatine and formononetin were confirmed to be the potential effective compounds of CAG in regulating 5-HT signaling pathway.</div></div><div><h3>Conclusion</h3><div>CAG exhibits therapeutic effect on IBS-D rats through regulating 5-HT signaling pathway in BGA. Tetrahydropalmatine and formononetin are major potential effective compounds. Our findings provide scientific basis for the clinical use and drug development of CAG for IBS-D.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156350"},"PeriodicalIF":6.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the mechanism and effective compounds of Changan Granule on diarrhea-predominant irritable bowel syndrome via regulating 5-hydroxytryptamine signaling pathway in brain-gut axis\",\"authors\":\"Qiaoxia Wang , Xiaoxuan Liu , Dongxing Song , Qingqing Wang , Mengjiao Wu , Zhihao Zhu , Mingxuan Jin , Siqi Liu , Jian Zhang , Rufeng Wang\",\"doi\":\"10.1016/j.phymed.2024.156350\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Changan Granule (CAG) is a drug product developed from a traditional Chinese medicine (TCM) empirical prescription for diarrhea-predominant irritable bowel syndrome (IBS-D). The action mechanism and effective compounds of CAG in the treatment of IBS-D are not well understood.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the effectiveness, action mechanism and effective compounds of CAG for treating IBS-D.</div></div><div><h3>Methods</h3><div>Network pharmacology was used to screen the related pathways and active compounds of CAG in the treatment of IBS-D. Neonatal mother-infant separation, acetic acid enema and colorectal dilation were employed to construct IBS-D model for <em>in vivo</em> study. The effectiveness of CAG was evaluated in accordance with the results of body weight measurement, fecal water content determination, abdominal withdraw reflex test, open field test, sucrose preference test, forced swimming test and hematoxylin-eosin (HE) staining. The protein and mRNA levels of key molecules regulated by CAG were assessed through enzyme-linked immunosorbent assay (ELISA), western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The active compounds from CAG screened by network pharmacology were investigated with Caco-2 and RIN-14B cell models <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Network pharmacological analysis showed that CAG regulated 5-hydroxytryptamine (5-HT) signaling pathway and tetrahydropalmatine, formononetin and corydaline might be the potential effective compounds. The validation experiments showed that CAG restored the decreased body weight, and alleviated intestinal sensitivity, low-grade inflammation, diarrhea, frequent defecation, anxiety and depression of IBS-D rats through regulating the expression levels of 5-HT, tryptophan hydroxylase (TPH)1/2, serotonin transporter (SERT), 5-hydroxytryptamine-3 and -4 receptors (5-HT<sub>3</sub>R and 5-HT<sub>4</sub>R) in brain-gut axis (BGA). Tetrahydropalmatine and formononetin were confirmed to be the potential effective compounds of CAG in regulating 5-HT signaling pathway.</div></div><div><h3>Conclusion</h3><div>CAG exhibits therapeutic effect on IBS-D rats through regulating 5-HT signaling pathway in BGA. Tetrahydropalmatine and formononetin are major potential effective compounds. Our findings provide scientific basis for the clinical use and drug development of CAG for IBS-D.</div></div>\",\"PeriodicalId\":20212,\"journal\":{\"name\":\"Phytomedicine\",\"volume\":\"136 \",\"pages\":\"Article 156350\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0944711324010055\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711324010055","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Exploring the mechanism and effective compounds of Changan Granule on diarrhea-predominant irritable bowel syndrome via regulating 5-hydroxytryptamine signaling pathway in brain-gut axis
Background
Changan Granule (CAG) is a drug product developed from a traditional Chinese medicine (TCM) empirical prescription for diarrhea-predominant irritable bowel syndrome (IBS-D). The action mechanism and effective compounds of CAG in the treatment of IBS-D are not well understood.
Purpose
This study aimed to investigate the effectiveness, action mechanism and effective compounds of CAG for treating IBS-D.
Methods
Network pharmacology was used to screen the related pathways and active compounds of CAG in the treatment of IBS-D. Neonatal mother-infant separation, acetic acid enema and colorectal dilation were employed to construct IBS-D model for in vivo study. The effectiveness of CAG was evaluated in accordance with the results of body weight measurement, fecal water content determination, abdominal withdraw reflex test, open field test, sucrose preference test, forced swimming test and hematoxylin-eosin (HE) staining. The protein and mRNA levels of key molecules regulated by CAG were assessed through enzyme-linked immunosorbent assay (ELISA), western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The active compounds from CAG screened by network pharmacology were investigated with Caco-2 and RIN-14B cell models in vitro.
Results
Network pharmacological analysis showed that CAG regulated 5-hydroxytryptamine (5-HT) signaling pathway and tetrahydropalmatine, formononetin and corydaline might be the potential effective compounds. The validation experiments showed that CAG restored the decreased body weight, and alleviated intestinal sensitivity, low-grade inflammation, diarrhea, frequent defecation, anxiety and depression of IBS-D rats through regulating the expression levels of 5-HT, tryptophan hydroxylase (TPH)1/2, serotonin transporter (SERT), 5-hydroxytryptamine-3 and -4 receptors (5-HT3R and 5-HT4R) in brain-gut axis (BGA). Tetrahydropalmatine and formononetin were confirmed to be the potential effective compounds of CAG in regulating 5-HT signaling pathway.
Conclusion
CAG exhibits therapeutic effect on IBS-D rats through regulating 5-HT signaling pathway in BGA. Tetrahydropalmatine and formononetin are major potential effective compounds. Our findings provide scientific basis for the clinical use and drug development of CAG for IBS-D.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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