Pedalitin could regulate lipid metabolism and attenuate inflammatory factors in a non-alcoholic fatty liver disease cell model

Wanying He , Yaying Yu , Hui He , Qian Huang , Zhiting Liu , Fan Yang , Lin Zhou
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Abstract

Nonalcoholic fatty liver disease (NAFLD) is an escalating global health issue, leading to liver fat accumulation, inflammation, fibrosis, and potential liver failure. In our preliminary network pharmacological study, it was hypothesized that Pedalitin (PED), a flavonoid found in black sesame plants, might exhibit protective effects against NAFLD. However, the effects and mechanisms of PED underlying its action on NAFLD are not yet fully understood. This study aimed to explore the potential effects and mechanisms of PED on NAFLD using a combination of network pharmacology, molecular docking, and the LO2 cell model. Potential targets for PED and NAFLD were predicted through public databases. Protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking was used to predict the target genes that could bind to PED. In vitro experiments using the LO2 cell model indicated that PED significantly reduced TG level (p ​< ​0.05) and the formation of lipid droplets. The expression levels of key factors in fatty acid metabolism (CPT2, HADH), inflammatory factors (IL-17, TNF-α), and the FOXO signaling pathway (EGFR, IRS1, AKT1, FOXO1) were significantly downregulated in LO2 cells treated with PED (p ​< ​0.05). In conclusion, PED may modulate local lipid metabolism and mitigate inflammatory responses through the FOXO signaling pathway.
在非酒精性脂肪肝细胞模型中,脚踏板可调节脂质代谢并减轻炎症因子
非酒精性脂肪性肝病(NAFLD)是一个不断升级的全球健康问题,可导致肝脏脂肪堆积、炎症、纤维化和潜在的肝衰竭。在我们初步的网络药理学研究中,我们假设在黑芝麻植物中发现的黄酮类化合物Pedalitin (PED)可能对NAFLD具有保护作用。然而,PED对NAFLD作用的影响和机制尚不完全清楚。本研究旨在通过网络药理学、分子对接和LO2细胞模型相结合的方法,探讨PED对NAFLD的潜在作用及其机制。通过公共数据库预测PED和NAFLD的潜在靶点。构建蛋白-蛋白相互作用(PPI)网络,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析。利用分子对接技术预测可能与PED结合的靶基因。体外LO2细胞模型实验表明,PED显著降低TG水平(p <;0.05)和脂滴的形成。在PED处理的LO2细胞中,脂肪酸代谢关键因子(CPT2、HADH)、炎症因子(IL-17、TNF-α)和FOXO信号通路(EGFR、IRS1、AKT1、FOXO1)的表达水平显著下调(p <;0.05)。综上所述,PED可能通过FOXO信号通路调节局部脂质代谢,减轻炎症反应。
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