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Abstract

Introduction

Barberry Root (Sankezhen, SKZ), a traditional Uyghur herb from Xinjiang, China, has been shown to alleviate diarrhea-predominant irritable bowel syndrome (IBS-D); however, its molecular mechanisms remain unclear. This study aimed to systematically predict SKZ’s therapeutic targets and pathways for IBS-D using computational and experimental integration.

Methods

Active SKZ compounds and targets were sourced from TCM-Suite, BATMAN-TCM, and related databases. IBS-D targets were identified DisGeNET and GeneCards, etc. Protein-Protein Interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking and 100-ns Molecular Dynamics (MD) simulations validated compound-target stability. (LPS-induced RAW264.7 macrophages) and (IBS-D model rats, isolated intestinal segments) experiments verified SKZ’s effects.

Results

Fifteen bioactive compounds and 85 overlapping targets were identified, with four key compounds [(R)-Reticuline, Ferulic acid 4-O-glucoside, Magnoflorine, SW 7] and 15 hub targets (, ESR1, EGF, ALB) prioritized. Enrichment analyses linked targets to inflammation and intestinal motility pathways. Docking showed strong binding affinities (<-8.0 kcal/mol), and MD simulations confirmed stability. SKZ suppressed inflammatory mediators, downregulated CHAT/C-FOS/5-HTR/5-HTR mRNA, and antagonized acetylcholine/barium chloride-induced intestinal contractions.

Discussion

The findings highlight SKZ’s synergistic role in ameliorating IBS-D multi-pathway regulation, consistent with existing research on inflammation and neurotransmission, though limitations include the need for further validation of individual compounds.

Conclusion

SKZ exerts synergistic therapeutic effects on IBS-D by ameliorating inflammation and regulating neurotransmission and intestinal motility, potentially NF-κB/MAPK, COX-2/PGE2, cholinergic/5-HT, and calcium/potassium channel pathways, forming a multidimensional network.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-09-15
2025-11-29

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/content/journals/cchts/10.2174/0113862073421977250903053304
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Decoding Barberry Root’s Therapeutic Network: A Synergistic Solution for IBS-D
Bentham Science Publishers ; https://doi.org/10.2174/0113862073421977250903053304
/content/journals/cchts/10.2174/0113862073421977250903053304
/content/journals/cchts/10.2174/0113862073421977250903053304
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  • Article Type:     Research Article
Keywords: molecular simulation ; multi-target therapy ; network pharmacology ; Barberry root ; experimental validation ; diarrhea-predominant irritable bowel syndrome (IBS-D)

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