Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism

Exessive drinking is commonly associated with a wide spectrum of liver injuries. The term alcoholic liver disease (ALD) is generally used to refer to this spectrum of hepatic abnormalities, and the term hepatic steatosis denotes early lesions. Puerariae Lobatae Radix (PLR) is a common traditional Chinese medicine and has been widely used as an efficient treatment for alcohol-induced damage. Flavonoids are the principal components of PLR that could potentially be responsible for the activation of alcohol metabolism and lipid-lowering effects. However, little is known about the mechanisms underlying their activity against alcoholic injury. In this study, PLR flavonoids (PLF) were obtained by microwave extraction. A 2% ethanol solution was used to establish a model of alcoholic fatty liver disease by exposure of zebrafish larvae for 32 h, and then the zebrafish were administered PLF and puerarin. The results showed that PLF and puerarin significantly decreased lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Moreover, PLF and puerarin downregulated the expression of genes related to alcohol and lipid metabolism (CYP2y3, CYP3a65, ADH8a, ADH8b, HMGCRB, and FASN), endoplasmic reticulum stress, and DNA damage (CHOP, EDEM1, GADD45αa, and ATF6) and reduced levels of inflammatory factors (IL-1β, TNF-α) in zebrafish larvae. PLF and puerarin increased the phosphorylation of AMP-activated protein kinase-α (AMPKα) and decreased the total protein level of ACC1. The findings suggested that PLF and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae by regulating alcohol and lipid metabolism, which was closely related to the regulation of the AMPKα-ACC signaling pathway. In conclusion, the study provided a possible therapeutic drug for ALD treatment.