Department of Endocrinology and Metabolism, the Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, Guangdong, China.
BMC Complement Med Ther. 2024 Aug 14;24(1):305. doi: 10.1186/s12906-024-04600-4.
There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear.
Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD.
The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein-protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments.
Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. DISCUSSION AND CONCLUSION: The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy.
目前尚无针对非酒精性脂肪性肝病（NAFLD）的特定临床药物。丹参-虎杖药对（SRDP）已广泛用于治疗慢性肝病。然而，SRDP 治疗 NAFLD 的机制尚不清楚。
基于网络分析和体外实验验证，研究 SRDP 对脂质沉积的影响，并探讨其治疗 NAFLD 的可能机制。
利用 TCMSP 平台筛选 SRDP 的活性代谢物及其相应靶点，利用 GeneCards 和 OMIM 数据库筛选 NAFLD 靶点，提取药物-疾病交集靶点，获取潜在靶点，构建药物-活性代谢物-靶点-疾病网络图谱。利用 DAVID 数据库对交集靶点进行 GO 和 KEGG 通路富集分析。通过体外实验验证核心活性代谢物和信号通路。
网络分析预测 SRDP 治疗 NAFLD 的 59 种活性代谢物和 89 个靶标。KEGG 通路富集分析得到 112 个信号通路，包括 PI3K-AKT 信号通路等。证实 SRDP 的核心活性代谢物木犀草素能有效降低 HepG2 脂肪性肝病细胞模型中的脂肪堆积和细胞内甘油三酯含量。木犀草素通过抑制 PI3K-AKT 信号通路磷酸化抑制 mTOR 通路，从而激活自噬，缓解 NAFLD。
本研究通过多靶点和信号通路验证和预测了 SRDP 各种活性代谢物治疗 NAFLD 的可能作用。SRDP 的核心活性代谢物木犀草素通过作用于 PI3K-AKT-mTOR 信号通路诱导自噬，缓解 NAFLD。
