In vivo study and in silico analysis of the hepatoprotective effects of an aqueous extract of Cucurbita pepo L. (Cucurbitaceae) leaves against acetaminophen-induced liver damage and oxidative stress in Wistar rats

Objectives The objectives were to study, in vivo, the hepatoprotective effects of Cucurbita pepo L. (Cucurbitaceae) leaves against acetaminophen-induced hepatocyte damage in Wistar rats, and to conduct an in silico analysis of molecular targets. Methods Hepatic toxicity was induced by oral administration of acetaminophen at a dose of 750 mg/kg to Wistar rats. An aqueous extract of Cucurbita pepo L. was administered orally for 8 days at doses of 100 and 200 mg/kg body weight to rats with hepatic toxicity. Biochemical and oxidative parameters were assessed in serum and liver homogenates. Key findings Serum levels of triglycerides, total cholesterol, cholesterol-C, and total protein increased (p<0.001) in rats treated with acetaminophen alone and were reduced (p<0.001) by the 100 and 200 mg/kg body weight doses of extract. The extract significantly reduced (p < 0.001) the acetaminophen-induced increase in serum transaminases, alkaline phosphatase, and total bilirubin in rats. At 100 and 200 mg/kg body weight, the extract restored (p<0.001) markers of oxidative stress (catalase, glutathione, and malondialdehyde). Histopathological examination confirmed hepatocellular protection, with reduced portal inflammation and recovery of liver architecture. The results of the docking analysis obtained from an exploratory study on a plant related to Cucurbita pepo revealed potential molecular interactions between target proteins and molecules that may be present in the aqueous extract of Cucurbita pepo. Conclusions These results suggest that Cucurbita pepo may possess hepatoprotective properties in vivo and, according to the preliminary computational study, may act on target proteins.