Evaluation of the In-Vivo Anti-Fibrotic Properties of the Leaf Extract of Indian Jujube (Ziziphus Mauritiana) on Chemically Induced Hepatic Fibrosis

Abstract

Worldwide, liver injury is a major public health issue. Thus, novel, effective, and preventive therapy are needed. Ziziphus Mauritiana (Z. mauritiana) is believed to treat numerous organ toxicities. This is due to its antioxidants. Chronic liver inflammation, such as non-alcoholic steatohepatitis, promotes liver fibrosis and mortality. However, no authorized liver fibrosis treatment exists. This study examined the antioxidant and liver-protective activities of hydroethanolic extracts from Z. mauritiana leaves (ZMLE). The study focused on the liver damage caused by 2-nitropropane (2-NP) in rats, namely fibrosis. We investigated the impact of ZMLE on preclinical models. The rats received intraperitoneal injections of 2-NP twice a week for a duration of 12 weeks. Following this, they were simultaneously treated with ZMLE at doses of 200, 400, and 800 mg/kg body weight daily for another 12 weeks. The anti-fibrotic effect was assessed using serological and tissue homogenate tests, including measurements of AST, ALT, ALP, reduced GSH, MDA, SOD, GPx, CAT, proinflammatory cytokines, tissue hydroxyproline content, CYP-450 content, UDPGT, Na+-K+-ATPase and Ca+-K+-ATPase activity. Additionally, histochemical analysis using H&E staining was performed. The oral administration of ZMLE, particularly at high doses, effectively reduced the occurrence and severity of liver toxicity induced by 2-NP. This was achieved by activating the liver's antioxidant defense mechanisms, regulating liver functions, and reducing the production of lipid peroxidation, pro-inflammatory mediators, and collagen content. Nevertheless, the extent of inhibition differed based on the dosage. This study provides evidence that ZMLE mitigates liver fibrosis through its antioxidant and anti-inflammatory properties.