Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 May 1;1222:123711. doi: 10.1016/j.jchromb.2023.123711. Epub 2023 Apr 7.
Hangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear. An integrated strategy based on metabolomics with network analysis and network pharmacology was developed to explore the potential molecular mechanism of HJ on ALI protection. Firstly, differential endogenous metabolites were screened and identified by metabolomics approach and metabolic pathway analysis was performed by MetaboAnalyst. Secondly, marker metabolites were used to construct metabolite-response-enzyme-gene networks and discover hub metabolites and potential gene targets in network analysis. Thirdly, hub genes through the protein-protein interaction (PPI) network were acquired by the aid of network pharmacology. Finally, the gene targets were taken to intersect with the relevant active ingredients for validation by molecular docking. In total, 48 flavonoids were identified in HJ, which were associated with 8 potential therapeutic targets in network pharmacological analysis. Biochemistry and histopathology analysis demonstrated that HJ exerted hepatoprotective effects. 28 biomarkers were successfully identified as possible biomarkers for the prevention of ALI. The sphingolipid metabolic pathway and the glycerophospholipid metabolic pathway was considered a crucial signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, phosphatidylcholine and sphingomyelin were considered as hub metabolites. Twelve enzymes and 38 genes were considered as potential targets in the network analysis. Based on the combined analysis above, HJ was shown to modulate 2 key upstream targets, including PLA2G2A and PLA2G4A. Molecular docking showed that active compounds of HJ had high binding affinity with these key targets. In conclusion, the flavonoid components of HJ can inhibit PLA2 and regulate glycerophospholipid and sphingolipid metabolism pathway to delay the pathological process of ALI, which may be a potential mechanism of HJ against ALI.
杭菊（HJ），即菊花的干头状花序，具有显著的保肝作用。然而，其防治急性肝损伤（ALI）的潜在作用机制尚不清楚。本研究采用基于代谢组学的整合策略，结合网络分析和网络药理学，探讨 HJ 防治 ALI 的潜在分子机制。首先，采用代谢组学方法筛选和鉴定差异内源性代谢物，并通过 MetaboAnalyst 进行代谢途径分析；其次，利用标记代谢物构建代谢物-反应-酶-基因网络，并在网络分析中发现关键代谢物和潜在基因靶点；然后，借助网络药理学获取蛋白-蛋白相互作用（PPI）网络中的关键基因；最后，将基因靶点与相关活性成分进行分子对接验证。共鉴定出 HJ 中的 48 种黄酮类化合物，通过网络药理学分析发现其中 8 种可能与治疗 ALI 相关的靶标。生物化学和组织病理学分析表明 HJ 具有保肝作用。成功鉴定出 28 种生物标志物，可作为预防 ALI 的潜在生物标志物。京都基因与基因组百科全书（KEGG）分析表明，鞘脂代谢和甘油磷脂代谢途径可能是重要的信号通路。此外，磷脂酰胆碱和神经鞘磷脂被认为是关键代谢物。网络分析中还确定了 12 种酶和 38 种基因作为潜在靶点。基于以上综合分析，HJ 可调节 2 个关键上游靶点，包括 PLA2G2A 和 PLA2G4A。分子对接表明，HJ 的活性化合物与这些关键靶点具有高结合亲和力。综上所述，HJ 的黄酮类成分可抑制 PLA2，调节甘油磷脂和鞘脂代谢途径，从而延缓 ALI 的病理过程，这可能是 HJ 防治 ALI 的潜在机制。
