Abstract
We investigated the effects of a Leonurus japonicus ethanol extract (LJE) on nonalcoholic fatty liver disease (NAFLD). An in vitro model of hepatic steatosis was treated with 1 mM free fatty acid (FFA) in HepG2 cells. An in vivo NAFLD model was established using C57BL/6 mice fed a high-fat diet (HFD) and administered LJE (100 or 200 mg/kg) orally for 14 weeks. LJE treatment suppressed lipid accumulation and intracellular triglyceride levels significantly in a concentration-dependent manner in HepG2 cells. Moreover, LJE significantly reduced the expression of sterol regulatory element binding protein 1-c, and its downstream genes, which are associated with lipogenesis, in HepG2 cells. In HFD-fed mice, LJE treatment decreased body weight significantly and decreased serum alanine transaminase levels to normal values, concurrent with a decrease in hepatic lipid accumulation. Furthermore, LJE supplementation ameliorated insulin sensitivity by decreasing serum glucose and insulin levels. LJE improved hepatic steatosis by increasing the expression of phosphorylated AMP-activated protein kinase and peroxisome proliferator-activated receptor-α in HFD-fed mice and FFA-treated HepG2 cells. The results suggested that LJE might be a potential therapeutic agent to treat NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with metabolic diseases [1]
NAFLD represents a wide range of pathological liver damage, from simple steatosis to steatohepatitis associated with inflammation, fibrosis, and cirrhosis [2,3]
SCD-1,cells, and further expression reduced in Leonurus japonicus ethanol extract (LJE)-treated. These results indicated that LJE treatment downregulated lipogenesis markers in free fatty acid (FFA)-induced HepG2 cells, further suggesting that the suppression of TG accumulation is involved in the LJE-induced accumulation
Summary
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with metabolic diseases [1]. Long-term HFD-induced NAFLD animal models provide useful information to test the therapeutic effects of various agents, as well as to elucidate the pathogenesis of NAFLD [5,6]. Pharmacological treatments for NAFLD include lipid-lowering agents (statins, fibrates), insulin sensitizers (metformin, thiazolidinediones), cytoprotective and antioxidant agents (bile acids, vitamin E), and anti-obesity drugs (orlistat) [9]. These drugs are not liver-specific agents and increase the risk of side effects caused by long-term ingestion. There has been no investigation of the effects of L. japonicus on NAFLD caused by HFD-induced obesity. We investigated the pharmacological effects of an L. japonicus ethanol extract (LJE) on the improvement of NAFLD via in vitro and in vivo models
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