Hepatoprotective activity of taraxacum officinale extract against CCl4-induced liver injury in rats

Carbon tetrachloride (CCl4), a former dry-cleaning solvent, is now restricted due to its well-documented hepatotoxicity, nephrotoxicity, and carcinogenicity. Exposure to CCl4 induces significant adverse effects and damages vital organs in both humans and animals, motivating research into herbal hepatoprotective agents as potential adjuncts for mitigating CCl4-induced liver injury. Although taraxacum officinale extract (TOE) has a history of traditional use in treating gastrointestinal disorders, its potential for hepatoprotection against CCl4-induced hepatic injury in rat models remains uninvestigated. Consequently, this study aimed to evaluate the antioxidant activity of TOE and its capacity to alleviate CCl4-induced liver damage. Consequently, this study investigated the antioxidant activity of TOE and its potential to alleviate CCl4-induced hepatic injury. A comparative analysis of extraction methods (ethanolic, chloroformic, ethyl acetate, petroleum ether, and aqueous) on TOE showed that ethanolic extraction had the highest concentrations of phenolic and flavonoid compounds. The ethanolic extract of TOE had the highest total phenolic content (800.8 mg GAE/g), total flavonoid content (18.58 mg QE/g), and DPPH radical scavenging activity (43.63 %). An in vivo study was conducted with 24 male rats, randomly assigned to four groups (n = 6 per group). Group 1 (control) received physiological saline (1 mL/kg b.w.) via oral gavage. Group 2 (CCl4) received CCl4 (1 mL/kg b.w.). Groups 3 (TOE100) and 4 (TOE200) received CCl4 (1 mL/kg b.w.) concurrently with TOE at dosages of 100 and 200 mg/kg b.w., respectively, for 8 weeks. Co-administration of both TOE dosages significantly attenuated the CCl4-induced elevation of liver enzymes and bilirubin (P < 0.05). Furthermore, TOE administration significantly reduced serum levels of TC, TG, and low-density lipoprotein cholesterol (LDL-C) in CCl4-treated rats (P < 0.05). Additionally, the TOE100 group exhibited significantly elevated serum high-density lipoprotein cholesterol (HDL-C) levels compared to the CCl4-treated group (P < 0.05). Both the TOE100 and TOE200 groups showed significantly reduced serum MDA concentrations and significantly increased activities of GSH, CAT, GSTs, and SOD compared to the CCl4-treated group (P < 0.05). Histopathological examination demonstrated that TOE exerted hepatoprotective effects, evidenced by the mitigation of CCl4-induced hepatocellular damage, inflammation, fibrosis, and steatosis. In silico docking studies revealed that catechin, naringenin, and chlorogenic acid, key constituents of TOE, exhibited strong binding affinities for the KEAP1 protein, with binding energies of -7.58, -7.09, and -6.83 kcal/mol, respectively. Molecular docking analysis with JAK2 showed naringenin with the highest binding energy (-6.01 kcal/mol), followed by catechin (-5.73 kcal/mol) and chlorogenic acid (-5.71 kcal/mol). The findings suggest that TOE exerts hepatoprotective effects against CCl4-induced liver injury, potentially through the modulation of antioxidant and oxidative stress markers and the KEAP1/JAK2 signaling pathways. This presents a potential therapeutic strategy for hepatic disorders.