Crataegus aronia prevents high‐fat diet‐induced hepatic steatosis in rats by activating AMPK‐induced suppression of SREBP1 and activation of PPARα

This study examined if the aqueous extract of Crataegus aronia (C. aronia) can prevent high‐fat diet (HFD)‐induced hepatic steatosis in rats by activating AMPK. Adult male Wistar rats were fed either a control diet or HFD for 12 weeks and treated either with vehicle (normal saline) or C. aronia extract (200 mg/kg/orally), daily. Also, hepatocytes were treated with increasing concentrations of the extract in the presence or absence of compound C (CC), an AMPK inhibitor. C. aronia prevented the increase in serum and hepatic lipids, reduced hepatic levels of reactive oxygen species, and increased hepatic glutathione and superoxide dismutase levels. It also downregulated the hepatic expression of SREBP1/2, fatty acid synthase, and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase but stimulated the activity of AMPK and levels of peroxisome proliferator‐activated receptor‐alpha. Similar effects were reported in the cultured cells, in a dose‐dependent manner but were prevented by CC. In conclusion, C. aronia ameliorates HFD‐induced hepatic steatosis and oxidative stress by activating AMPK. Practical applications The use of the aqueous extract of Crataegus aronia has been extensively used during the last years in traditional medicine to treat chronic disorders including nonalcoholic fatty liver disease. The findings of this study support these findings and suggest that oral administration of C. aronia aqueous extract has potent hypoglycemic effect and demonstrate the mechanism of action mimics such drugs such as metformin and involves activation of AMPK and peroxisome proliferator‐activated receptor‐alpha. These findings are very encouraging for further biochemical analysis and isolation of active ingredients responsible for these effects to be used in more clinical trials. A graphical summarizes the hepatoprotective and anti‐steatotic effect of Crataegus aronia (C. aronia) in high fat‐diet rats. In the figure, C. aronia exerts an antioxidant effect and scavenges reactive oxygen species by stimulating glutathione (GSH) and superoxide dismutase (SOD) levels. This antioxidant potential of C. aronia also inhibits SREBP1/2 and their downstream lipogenic target genes including fatty acid synthase (FAS), acetyl‐Coenzyme A carboxylase (ACC‐1), 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCoAR). Besides, C. aronia downregulates SREBP1/2 and stimulates peroxisome proliferator‐activated receptor‐alpha (PPARα) and fatty acids oxidation by activating AMPK.