Asiatic Acid Ameliorates Hepatic Lipid Accumulation and Insulin Resistance in Mice Consuming a High-Fat Diet

Abstract

Effects of asiatic acid (AA) at 10 or 20 mg/kg/day upon hepatic steatosis in mice consuming a high-fat diet (HFD) were examined. AA intake decreased body weight, water intake, feed intake, epididymal fat, and plasma and hepatic triglyceride levels in HFD-treated mice (P < 0.05). HFD enhanced 2.85-fold acetyl coenzyme A carboxylase (ACC1), 3.34-fold fatty acid synthase (FAS), 3.71-fold stearoyl CoA desaturase (SCD)-1, 3.62-fold 3-hydroxy-3-methylglutaryl coenzyme A reductase, 2.91-fold sterol regulatory element-binding protein (SREBP)-1c, and 2.75-fold SREBP-2 expression in liver (P < 0.05). Compared with HFD groups, AA intake at two doses reduced 18.9-45.7% ACC1, 25.1-49.8% FAS, 24.7-57.1% SCD-1, and 21.8-53.3% SREBP-1c protein expression (P < 0.05). Histological results indicated AA intake at two doses reduced hepatic lipid accumulation and inflammatory infiltrate. HFD increased hepatic production of reactive oxygen species, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as decreased hepatic glutathione content and glutathione peroxidase and catalase activities (P < 0.05). AA intake at two doses reversed these alterations (P < 0.05). AA intake suppressed 32.4-58.8% nuclear factor kappa (NF-κ)B p65 and 24.2-56.7% p-p38 expression (P < 0.05) and at high dose down-regulated 29.1% NF-κB p50 and 40.7% p-JNK expression in livers from HFD-treated mice. AA intake at two doses lowered plasma insulin secretion and HOMR-IR (P < 0.05). These results suggest that AA is a potent hepatic protective agent against HFD-induced hepatic injury.

SIRT3 Deficiency Promotes High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease in Correlation with Impaired Intestinal Permeability through Gut Microbial Dysbiosis

“…Additionally, hepatic biomarkers associated with carbohydrate and lipid metabolism, such as PEPCK, G6P, ACC1, FAS, and SCD‐1 mRNA levels, were significantly increased under the HFD condition. This finding is strongly supported by a previous study . Accordingly, a higher liver TG concentration was found in the SIRT3KO HFD and WT HFD groups, concomitant with increases in the mRNA expression of genes associated with glucose utilization (GLCK, SREBP‐1), fatty acid synthesis (FAS, ACC1, and SCD‐1), and lipid lipogenesis (FAT/CD36) .…”

Biopharmaceutical and pharmacokinetic characterization of asiatic acid in Centella asiatica as determined by a sensitive and robust HPLC–MS method

“…Asiatic acid is a triterpenoid component found in Centella asiatica Pakdeechote et al, 2014;Ramachandran et al, 2014), which is an important herb used widely in China and gradually becomes popular in the west (Gohil et al, 2010;Kavitha et al, 2011;Orhan, 2012;Xu et al, 2013;Chen et al, 2014;Yan et al, 2014). Previous studies have demonstrated that asiatic acid could be used for wound healing, various skin conditions, inflammatory, diabetic, hyperlipidemic, and also for anti-depressant, relieving anxiety and improving cognition (Jeong, 2006;Tang et al, 2012;Xu et al, 2012;Zhang et al, 2012;Wei et al, 2013).…”

Bioactivities of Eriobotrya japonica (Thunb.) Lindl. Leaf and Its Triterpenes

“…Since GOAT recognizes fatty acyl-coenzyme (Co)A molecules, such as octanoyl-, hexanoyl-, and decanoyl-CoA [43], we speculated that the carboxyl group in a molecule is an important functional group for this inhibitory effect. Triterpenes, such as asiatic acid, betulinic acid, corosolic acid, glycyrrhetinic acid, oleanolic acid, and ursolic acid have shown antiobesity effects in mice fed a high-fat diet [44][45][46][47][48][49]. Like fatty acids, these triterpenes also have a carboxyl group in their structure, suggesting that they could also suppress octanoylated ghrelin production.…”