School of Nursing, Shandong Second Medical University, Weifang, 261021, Shandong, China.
School of Nursing, Jining Medical University, Jining, 272067, Shandong, China.
Curr Pharm Des. 2024;30(41):3291-3310. doi: 10.2174/0113816128328422240820105654.
Compound 861 (Cpd861) is a traditional Chinese herbal compound for the treatment of hepatic fibrosis (HF). In the current investigation, Cpd861 has been demonstrated to have an underlying molecular mechanism and material foundation for the treatment of HF through network pharmacology, Mendelian randomization (MR), and molecular docking.
Public databases were consulted for Cpd861 constituents and HF targets. Protein-protein interactions (PPIs) were established using STRING software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To elucidate the causal relationship between potential targets and liver injury, MR was used as a methodological tool. Finally, a molecular docking analysis was conducted between the active compound and the key target.
We obtained 174 active ingredients and 113 intersecting genes. Through the PPI network, high-degree targets were identified, namely CTNNB1, ESR1, FOS, MDM2, CCND1, TP53, RELA, and BCL2. As shown by GO and KEGG pathway enrichment analyses, Cpd861 functions through xenobiotic stimulus and oxidative stress-related genes, as well as the PI3K-AKT and non-alcoholic fatty liver disease (NAFLD) signaling pathways. The results of MR showed that MDM2 and BCL2 had a causal relationship with liver injury. Molecular docking results showed that several active compounds in Cpd861 were stably bound to BCL2.
This study made predictions regarding the efficacious components, as well as potential targets and pathways of Cpd861 in the therapy of HF. This will open up a new perspective for further investigation of the molecular mechanism of Cpd861 in the treatment of HF.
复方 861（Cpd861）是一种治疗肝纤维化（HF）的中药复方。在当前的研究中，通过网络药理学、孟德尔随机化（MR）和分子对接，已经证明 Cpd861 具有治疗 HF 的潜在分子机制和物质基础。
从公共数据库中查询 Cpd861 成分和 HF 靶点。使用 STRING 软件构建蛋白质-蛋白质相互作用（PPI）网络，然后进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。为了阐明潜在靶点与肝损伤之间的因果关系，我们将 MR 作为一种方法学工具。最后，对活性化合物与关键靶标之间进行了分子对接分析。
我们获得了 174 种活性成分和 113 个相交基因。通过 PPI 网络，确定了高程度的靶点，即 CTNNB1、ESR1、FOS、MDM2、CCND1、TP53、RELA 和 BCL2。GO 和 KEGG 通路富集分析表明，Cpd861 通过与外来刺激和氧化应激相关的基因以及 PI3K-AKT 和非酒精性脂肪性肝病（NAFLD）信号通路发挥作用。MR 的结果表明，MDM2 和 BCL2 与肝损伤有因果关系。分子对接结果表明，Cpd861 中的几种活性化合物能稳定地与 BCL2 结合。
本研究预测了 Cpd861 治疗 HF 的有效成分、潜在靶点和通路，为进一步研究 Cpd861 治疗 HF 的分子机制开辟了新的视角。
