Veratrilla Bailloniifranch Could Alleviate Lipid Accumulation In Lo2 Cells By Regulating Oxidative, Inflammatory, And Lipid Metabolic Signaling Pathways

FRONTIERS IN PHARMACOLOGY(2020)

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摘要
Based on the pathological theory of lipid metabolism and using network pharmacology, this study was designed to investigate the protective effect of water extract ofVeratrilla baillonii(WVBF) on non-alcoholic fatty liver disease (NAFLD) model using LO2 cells and to identify the potential mechanism underlying the effect. The components ofV. bailloniiwere identified from the public database of traditional Chinese medicine systems pharmacology database (TCMSP). Cytoscape software was used to construct the related composite target network. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out for critical nodes. The BioGPS database was used to determine the distribution of the target in tissues and organs. Moreover, the inhibitory effect ofV. bailloniiwas further investigated using anin vitrohepatocyte NAFLD model. Fourteen active components were then selected from the 27 known compounds ofV. baillonii. The targets of gene enrichment analysis were mainly distributed in the lipid catabolism-related signaling pathway. Network analysis revealed that five target genes of TNF, MAPK8, mTOR, NF-kappa B, and SREBP-1c were key nodes and played important roles in this process. Organ localization analysis indicated that one of the core target site ofV. bailloniiwas liver tissue. The results of thein vitrostudy revealed that WVBF can alleviate the inflammatory response and lipid accumulation in LO2 hepatocytes by inhibiting oxidative stress and the adipocytokine signaling pathway. Genes and proteins related to the lipid synthesis, such as SREBP-1C, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN), were significantly decreased, and PPAR alpha expression is significantly increased with WVBF administration. In conclusion,V. bailloniimay regulate local lipid metabolism and attenuate oxidative stress and inflammatory factors through the PPAR alpha/SREBP-1c signaling pathway. The present study also indicates that multiple components ofV. bailloniiregulate multiple targets and pathways in NAFLD. The findings highlight the potential ofV. bailloniias a promising treatment strategy for nonalcoholic fatty liver injury.
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关键词
nonalcoholic fatty liver, lipid metabolism, amarogentin, network pharmacology, Veratrilla baillonii Franch
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