Hepatoprotective Potential of Eremanthin by Modulating Keap1/Nrf2/ARE Signaling in CCl 4 -Induced Liver Toxicity

Abstract Liver diseases are one of the severe health issues that cause fatality and illness globally. The situation has gotten worse and the available treatments have a variety of side effects. The researchers are focusing for plant-based hepatotherapeutic drugs because of their easy availability and fewer side effects. Eremanthin is a sesquiterpene compound isolated from some medicinal plants, reported to possess antioxidant and anti-inflammatory properties. The current study aimed to evaluate the hepatoprotective effects of this compound on liver damage induced by carbon tetrachloride (CCl4) in rats, focusing on the modulation of the Keap1/Nrf2/ARE signaling pathway. Fifty rats were divided into five groups of ten. Group I served as the negative control with no treatment. Groups II, III, IV, and V received a single intraperitoneal injection of CCl4 (0.5 ml/kg in olive oil at a 1:1 ratio). Group III rats were treated with silymarin, a standard hepatoprotective agent, while Groups IV and V received Eremanthin at doses of 20 mg/kg and 40 mg/kg, respectively, for 21 days. The results indicated that Eremanthin significantly (p < 0.05) reduced serum levels of liver enzymes and bilirubin in a dose-dependent manner compared to the positive control. Additionally, both Eremanthin-treated groups exhibited a marked decrease (p < 0.05) in total oxidative stress. Histopathological analysis revealed that Eremanthin has the potential to protect hepatocytes from CCl4-induced damage and enhances the expression of Nrf2, Keap1, HO1, and NQO1 genes. These findings suggest that Eremanthin possesses hepatoprotective properties by modulating the Keap1/Nrf2/ARE signaling pathway in a rat model of CCl4-induced liver damage.