Fermented Rhus Verniciflua Stokes Extract Alleviates Nonalcoholic Fatty Liver through the AMPK/SREBP1/PCSK9 Pathway in HFD-Induced Nonalcoholic Fatty Liver Animal Model

Abstract

Background: We have previously reported the anti-hepatic lipogenic effect of fermented Rhus verniciflua stokes extract (FRVE) in an oleic-acid-treated HepG2 cell model. Methods: Herein, we advanced our understanding and evaluated the impact of FRVE in HFD-fed C57BL/6 mice using an animal model of nonalcoholic fatty liver disease (NAFLD). Milk thistle extract was used as a positive control to compare the effects of FRVE. Results: FRVE decreased body weight, intra-abdominal fat weight, and liver weight. Furthermore, FRVE decreased HFD-induced elevated serum levels of ALT, AST, TC, and TG, and downregulated the increase in hepatic lipid accumulation and TG levels. FRVE reduced hepatic SREBP-1, PCSK-9, SREBP-2, and ApoB mRNA levels. IHC data showed that FRVE reduced the levels of nucleic SREBP-1, increased the levels of LDLR, and upregulated the expression of p-AMPK. Conclusion: Overall, these results demonstrate the anti-hepatic lipidemic effect of FRVE in an animal model. These findings are consistent with our previous study and strongly suggest that FRVE exerts anti-hepatic lipogenic effects by activating AMPK.

Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis

“…A recent study revealed that SREBF1 is activated through zinc finger and BTB domain-containing 7A (ZBTB7A), which causes lipid accumulation and progression of NAFLD [ 63 ]. Numerous studies have reported that SREBF1 is a potential target influencing NAFLD, as evidenced by administration of various interval treatments [ 64 – 66 ]. A recent study in 2021 by Elsayed et al indicated that SREBF1 elevation is a risk factor in the progression of NAFLD and that, following treatment of NAFLD, this gene was downregulated.…”

Effect of fermented Rhus verniciflua stokes extract on liver function parameters in healthy Korean adults: a double-blind randomized controlled trial

“…On the other hand, there are no clinical studies on liver function. Lee et al reported that FRVE has an anti-hepatic lipidemic effect by upregulating AMPK in cell and animal models [ 8 , 11 ]. In particular, they confirmed in an animal model that the levels of ALT, AST, TC, and TG decreased when animals with nonalcoholic fatty liver ingested FRVE [ 8 ].…”

“…Lee et al reported that FRVE has an anti-hepatic lipidemic effect by upregulating AMPK in cell and animal models [ 8 , 11 ]. In particular, they confirmed in an animal model that the levels of ALT, AST, TC, and TG decreased when animals with nonalcoholic fatty liver ingested FRVE [ 8 ]. ALT and AST are blood indicators that increase during liver damage and are important parameters that can predict the state of liver diseases such as hepatocellular disease or hepatitis [ 18 ].…”

“…In the experimental study, the conditions for using a dose of 2000 mg/kg or less of FRVE were established based on the results of the toxicity test conducted by the ChemOn Preclinical Research Center (Gyeonggi-do, Korea), and the effective concentration of FRVE in this study was derived based on a previous study [ 8 , 10 , 11 ].…”

“…FRVE has been reported to have anti-hepatic lipidemic effects through the activation of AMPK [ 7 ]. Furthermore, Lee et al reported in an animal model, in which the formation of a nonalcoholic fatty liver was induced by a high-fat diet, that ingestion of FRVE reduced liver-related parameters, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and reduced lipid-related parameters such as total cholesterol (TC) and triglycerides (TG) [ 8 ]. However, the effect of FRVE intake on liver function parameters has not been identified in humans.…”