College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
J Tradit Chin Med. 2022 Oct;42(5):788-794. doi: 10.19852/j.cnki.jtcm.20220815.003.
To study therapeutic effect of kaempferol on metabolic associated fatty liver disease (MAFLD) by network pharmacology and molecular docking combined with cell experiments.
First, use the SwissTargetPrediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the GeneCards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction (PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol; In cell experiment, oleic acid induced steatosis in HepG2 cells, which was intervened by kaempferol, the level of triglyceride (TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot.
The results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B (PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B (AKT1), pros-taglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation.
This study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD.
通过网络药理学和分子对接结合细胞实验研究山奈酚治疗代谢相关脂肪性肝病（MAFLD）的疗效。
首先，使用 SwissTargetPrediction 数据库预测山奈酚的靶点，通过 Disgenet 数据库和 GeneCards 数据库收集 MAFLD 的靶点。然后，通过基因本体（GO）和京都基因与基因组百科全书富集分析山奈酚与 MAFLD 的共同靶点，通过 string 数据库构建蛋白质-蛋白质相互作用（PPI）网络，得到关键靶点，并对关键靶点与山奈酚进行分子对接；在细胞实验中，油酸诱导 HepG2 细胞脂肪变性，用山奈酚干预，检测甘油三酯（TG）水平，油红 O 染色观察脂滴沉积，Western blot 检测蛋白表达。
结果表明，山奈酚与 MAFLD 共有 33 个共同靶点。GO 的生物学过程与蛋白激酶 B、细胞凋亡、炎症因子、脂氧合酶等的调节有关。其作用途径与磷脂酰肌醇-3-激酶和蛋白激酶 B（PI3K-AKT）信号通路、缺氧诱导因子 1 信号通路、叉头框蛋白 O 信号通路、AMP 激活蛋白激酶信号通路、肿瘤坏死因子信号通路等有关，关键靶点为蛋白激酶 B（AKT1）、前列腺素 G/H 合酶 2、基质金属蛋白酶-9、表皮生长因子受体，山奈酚与 4 个关键靶点的分子对接显示出良好的结合性能。细胞实验表明，山奈酚能降低细胞 TG 水平，减少脂滴沉积，增加 PI3K、AKT 和 beclin-1 的表达，降低 caspase-3 和核因子-κB 的表达。山奈酚通过调节 PI3K-AKT 信号通路调节细胞自噬、凋亡和炎症，从而治疗 MAFLD。
本研究表明，山奈酚可调节脂肪细胞模型的脂质代谢、减少细胞凋亡、调节炎症和自噬，揭示了山奈酚治疗 MAFLD 的作用机制，为治疗 MAFLD 提供了天然产物候选药物。
