Abstract
Allicin has been well documented to exhibit a wide spectrum of biological activities, especially lipid-lowering activity, as a promising candidate for the management of nonalcoholic fatty liver disease (NALFD). However, the mechanisms underlying the therapeutic effects of allicin require further investigation. It is tempting to think of combining network pharmacology and experimental validation to investigate the mechanism by which allicin ameliorates lipid metabolism disorder in HepG2 cells. We established a cell model of hepatic steatosis induced by PA to investigate the antisteatotic effects of allicin. The studies showed that allicin reduced PA-induced lipid accumulation using Nile red staining and TC and TG assays. Then, 219 potential targets of allicin were successfully predicted by PharmMapper. According to Reactome Pathway Analysis, 44 potential targets related to lipid metabolism were screened out. Molecular signaling cascades mediated by allicin included PPARA, PPARG, FABP4, and FABP6 by cytoHubba and qPCR analysis. Results revealed that allicin activated the gene expression of PPARA and FABP6 and suppressed the gene expression of FABP4 and PPARG. Thus, the present study united the methods of network pharmacology and experimental validation to investigate the protein targets of allicin on PA-induced lipid metabolism disorders to supply a reference for related application for the first time.
Highlights
Lipid metabolism disorders are common pathological processes in various clinical diseases and are characterized by abnormal changes in the content and/or arrangement of various kinds of lipoprotein [1], including elevations in total cholesterol (TC) and triglycerides (TG) [2]
PharmMapper server is a freely accessed web server designed to identify potential target candidates for the given small molecules using pharmacophore mapping approach [8, 9, 14]. e results of the network pharmacology method provide a basis for understanding the mechanism of action of allicin
We found that allicin reduced lipid accumulation in a dose-dependent response in HepG2 cells
Summary
Lipid metabolism disorders are common pathological processes in various clinical diseases and are characterized by abnormal changes in the content and/or arrangement of various kinds of lipoprotein [1], including elevations in total cholesterol (TC) and triglycerides (TG) [2]. Adjusting abnormal lipid metabolism is a practical procedure to slow or prevent the degeneration of systemic conditions. It is recommended that advantageous dietetic components make an important impact on the prevention and therapy of lipid metabolism disorder [5]. Allicin is produced by an enzymatic reaction when raw garlic is crushed or chopped. Allicin showed antioxidant role on Nile tilapia and stem cells. It has been proved in our previous research that allicin could reduce lipid droplets induced by 1,3-DCP in HepG2 cells, recommending allicin as a potential candidate for handling of abnormal lipid metabolism [8]. The mechanisms underlying the therapeutic effects of allicin require further investigation
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