AUTHOR=Zhai Leilei , Yang Weiming , Li Dianrong , Zhou Wei , Cui Min , Yao Ping 

TITLE=Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome

JOURNAL=Journal of Pharmacy & Pharmaceutical Sciences

VOLUME=Volume 26 - 2023

YEAR=2023

URL=https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences/articles/10.3389/jpps.2023.11225

DOI=10.3389/jpps.2023.11225

ISSN=1482-1826

ABSTRACT=Background: Rhubarb Peony Decoction (RPD) is a well-known Traditional Chinese Medicine (TCM) formula, which has been widely applied in treating ulcerative colitis (UC). UC and irritable bowel syndrome (IBS) share various similarities in clinical symptoms and mechanisms. We supposed that RPD may also play a crucial therapeutic role in IBS. However, the interaction of bioactives from RPD with the common targets involved in UC and IBS remains unclear. It was necessary to clarify the potential pharmacological mechanism of RPD in the treatment of IBS and UC overlap syndrome.
Methods: The active components and targets of RPD were retrieved from ETCM, TCMSP, BATMAN-TCM, and TCM databases. The disease targets were screened by searching the DrugBank, OMIM, TTD, and PharmGKB databases. PPI network analysis was performed and visualized via the STRING platform and Cytoscape software. GO (Gene Ontology) and KEGG
(Kyoto Encyclopedia of Genes and Genomes) enrichment analyses of the hub genes of RPD were predicted to elucidate the potential molecular mechanism. Subsequently, molecular docking was carried out to verify the combination of active compounds with core targets.
Results: By integrating all targets of RPD and disease, a total of 31 bioactive ingredients were identified containing quercetin, kaempferol, aloe-emodin, beta-sitosterol, and (+)-catechin, etc. JUN, TP53, MAPK1, RELA, MYC, and ESR1 were identified as potential therapeutic targets among 126 common drug-disease-related targets. They were enriched in the “AGE-RAGE signaling pathway in diabetic complications”, “NF-kappa B signaling pathway”, and “MAPK signaling pathway”.  Additionally, the main active ingredients succeeded in binding to the hub targets via molecular docking, further verifying the anti-inflammation and antioxidation effects.
Conclusions: RPD may exert the overall treatment effect for UC and IBS overlap syndrome via the biological mechanism of “multi-ingredients, multi-targets, and multi-pathways” on inflammation, oxidative stress, immune, oncogenicity, and gut microbiota dysbiosis.