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

• Published in: Current pharmaceutical design Vol. 30; no. 14; p. 1085
• Main Authors: Liu, Binbin, Zhang, Jie, Wang, Xiaoqi, Ye, Wei, Yao, Jiaming
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2024
• Subjects: Animals; Chromatography, High Pressure Liquid; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Disease Models, Animal; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Enema; Male; Molecular Docking Simulation; Network Pharmacology; Rats; Rats, Sprague-Dawley; rho GTP-Binding Proteins; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - antagonists & inhibitors; rhoA GTP-Binding Protein - metabolism; Signal Transduction - drug effects; Yu's enema formula; RhoA/ROCK pathway; intestinal mucosal barrier; network pharmacology; experiment verification; Ulcerative colitis
• ISSN: 1873-4286
• DOI: 10.2174/0113816128290586240315071044

The traditional Chinese medicine formula, Yu's Enema Formula (YEF), has demonstrated potential in the treatment of Ulcerative Colitis (UC).
This study aimed to unveil the anti-UC mechanisms of YEF.
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
validation, a UC rat model was employed.
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.
experiments suggested that YEF has the potential to alleviate UC symptoms and protect the intestinal mucosal barrier by inhibiting the RhoA/ROCK pathway.
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.