Hawthorn leaf flavonoids alleviate nonalcoholic fatty liver disease by enhancing the adiponectin/AMPK pathway

Hawthorn (Crataeguspinnatifida) belongs to the genus Rosaceae family of plants. The hawthorn leaf, Crataeguspinnatifida Bunge, is used for both condiment and medicinal purposes to prevent and treat metabolic dysfunctions, such as hyperlipidemia, hypertension, and cardiovascular disease in traditional Chinese medicine. However, its effects on nonalcoholic fatty liver disease (NAFLD) remain obscure. The purpose of the present study was to investigate the protective effect of hawthorn leaf flavonoids (HLF), the dominant bioactive extracts of hawthorn leaves, on high fat diet (HFD)-induced hepatic steatosis and to elucidate its underlying mechanisms. HLF supplementation significantly lowered body weight, liver weight, liver/body weight ratio, improved serum parameters and liver dysfunction and markedly decreased hepatic lipid accumulation in HFD-fed rats. In addition, HLF intervention dramatically increased circulating adiponectin levels and up-regulated the expression of adiponectin receptors, particularly adiponectin receptor 2 (AdipoR2) in the liver. Moreover, adenosine monophosphate (AMP)-activated protein kinase (AMPK) was also activated, as well as AMPK-mediated alteration of sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor α (PPARα) and their downstream targets. Taken together, our data suggest that HLF ameliorates hepatic steatosis by enhancing the adiponectin/AMPK pathway in the liver of HFD-induced NAFLD rats.