基于网络药理学、高效液相色谱分析和实验验证探讨于氏灌肠方通过阻断 RhoA/ROCK 通路治疗溃疡性结肠炎的作用机制。
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.
机构信息
Department of Digestion, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
出版信息
Curr Pharm Des. 2024;30(14):1085-1102. doi: 10.2174/0113816128290586240315071044.
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 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. 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.
背景
中药方剂“榆槐灌肠液（YEF）”在溃疡性结肠炎（UC）的治疗中显示出了潜力。
目的
揭示 YEF 治疗 UC 的作用机制。
方法
利用公共数据库，获得 YEF 和 UC 相关靶点。通过 clusterProfiler 和 Reactome 进行 GO 和 KEGG 分析。STRING 数据库构建 PPI 网络，使用 cytoHubba 选择枢纽靶点。采用 R 软件进行差异表达和相关性分析，用 PyMOL 和 AutoDock 进行分子对接。采用 HPLC 分析鉴定 YEF 中的化合物。通过 UC 大鼠模型进行验证。
结果与讨论
鉴定出 495 个 YEF-UC 重叠靶点。GO 和 KEGG 分析表明，这些靶点富集于外源性刺激反应、肽反应、正 MAPK 级联调节、白细胞介素相关信号、TLR4 级联等通路。枢纽靶点包括 CTNNB1、JUN、MAPK1、MAPK3、SRC、STAT3、TLR4、TP53 和 RELA，它们之间常相互作用。分子对接显示槲皮素与 CTNNB1、MAPK1、MAPK3、SRC、STAT3、TLR4 和 TP53 的结合亲和力较强，与 HPLC 分析一致。实验表明，YEF 通过抑制 RhoA/ROCK 通路，可能减轻 UC 症状，保护肠黏膜屏障。
结论
YEF 可能通过靶向 CTNNB1、MAPK1、MAPK3、SRC、STAT3、TLR4 和 TP53 来保护 UC 中的肠黏膜屏障，同时阻断 RhoA/ROCK 通路。
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