Exploration of the Mechanisms Underlying Yu's Enema Formula in Treating Ulcerative Colitis by Blocking the RhoA/ROCK Pathway Based on Network Pharmacology, High-performance Liquid Chromatography Analysis, and Experimental Verification

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BACKGROUND: The traditional Chinese medicine formula, Yu's Enema Formula (YEF), has demonstrated potential in the treatment of Ulcerative Colitis (UC).

OBJECTIVE: This study aimed to unveil the anti-UC mechanisms of YEF.

METHODS: Utilizing public databases, we obtained YEF and UC-related targets. GO and KEGG analyses were conducted via clusterProfiler and Reactome. The STRING database facilitated the construction of the PPI network, and hub targets were selected using cytoHubba. We used R software for differential expression and correlation analyses, and molecular docking was performed with PyMOL and AutoDock. HPLC analysis identified the compounds in YEF. For in vivo validation, a UC rat model was employed.

RESULTS AND DISCUSSION: 495 YEF-UC overlapping targets were identified. GO and KEGG analyses indicated enrichment in exogenous stimuli response, peptide response, positive MAPK cascade regulation, interleukin- related signaling, and the TLR4 cascade. Hub targets included CTNNB1, JUN, MAPK1, MAPK3, SRC, STAT3, TLR4, TP53, and RELA, which were often interconnected. Molecular docking revealed quercetin's strong binding affinity with CTNNB1, MAPK1, MAPK3, SRC, STAT3, TLR4, and TP53, consistent with HPLC analysis. In vivo experiments suggested that YEF has the potential to alleviate UC symptoms and protect the intestinal mucosal barrier by inhibiting the RhoA/ROCK pathway.

CONCLUSION: YEF may safeguard the intestinal mucosal barrier in UC by targeting CTNNB1, MAPK1, MAPK3, SRC, STAT3, TLR4, and TP53, while blocking the RhoA/ROCK pathway.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Current pharmaceutical design - (2024) vom: 20. März

Sprache:

Englisch

Beteiligte Personen:

Liu, Binbin [VerfasserIn]
Zhang, Jie [VerfasserIn]
Wang, Xiaoqi [VerfasserIn]
Ye, Wei [VerfasserIn]
Yao, Jiaming [VerfasserIn]

Links:

Volltext

Themen:

Experiment verification
Intestinal mucosal barrier
Journal Article
Network pharmacology
RhoA/ROCK pathway.
Ulcerative colitis
Yu's enema formula

Anmerkungen:

Date Revised 25.03.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.2174/0113816128290586240315071044

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370131126