Decoding Barberry Root's Therapeutic Network: A Synergistic Solution for IBS-D

Area of Science:

• Pharmacology
• Computational Biology
• Gastroenterology

Background:

• Diarrhea-predominant irritable bowel syndrome (IBS-D) is a prevalent gastrointestinal disorder.
• Traditional Uyghur medicine utilizes Barberry Root (Sankezhen, SKZ) for IBS-D treatment.
• The molecular mechanisms underlying SKZ's efficacy for IBS-D are not well understood.

Purpose of the Study:

• To computationally predict and experimentally validate the therapeutic targets and molecular pathways of SKZ for IBS-D.
• To elucidate the synergistic mechanisms of SKZ in alleviating IBS-D symptoms.

Main Methods:

• Bioactive compounds and targets of SKZ were identified using multiple databases (TCM-Suite, BATMAN-TCM).
• IBS-D targets were collected from DisGeNET and GeneCards.
• Network pharmacology (PPI, GO, KEGG) and molecular docking/dynamics simulations were employed.
• In vitro (macrophages) and in vivo (IBS-D rat model) experiments were conducted for validation.

Main Results:

• Fifteen active compounds and 85 overlapping targets were identified, prioritizing four key compounds and 15 hub targets.
• Enrichment analyses indicated SKZ targets are involved in inflammation and intestinal motility pathways.
• SKZ demonstrated anti-inflammatory effects, downregulated key genes (CHAT, C-FOS, 5-HT3R, 5-HT4R), and inhibited intestinal contractions.

Conclusions:

• SKZ exhibits synergistic effects in ameliorating IBS-D through multi-pathway regulation.
• The herb potentially acts via pathways involving inflammation (NF-κB/MAPK), neurotransmission (cholinergic/5-HT), and ion channels.
• Findings support SKZ's therapeutic role in IBS-D, warranting further investigation of individual compounds.