An aqueous extract of Stevia rebaudiana variety Morita II prevents liver damage in a rat model of cirrhosis that mimics the human disease

Introduction and aim: Stevia has exhibited antioxidant, antihyperglycemic, antihypertensive and anti-inflammatory properties in several in vivo and in vitro models. The objective of this study was to investigate the ability of an aqueous extract of stevia (AES) to prevent experimental cirrhosis in rats and to explore its mechanism of action. Materials and methods: Liver cirrhosis was induced by administering carbon tetrachloride (CCl₄) (400 mg/kg by i.p. injection 3 times a week for 12 weeks); AES was administered (100 mg/kg by gavage daily) during the CCl₄ treatment. Fibrosis was evaluated with histological, biochemical and molecular approaches, and liver damage was assessed with standardized procedures. The profibrotic pathways were analyzed by western blotting, qRT-PCR and immunohistochemistry. Results and conclusions: Chronic CCl₄ administration increased nuclear factor kappa B (NF-κB) and proinflammatory cytokine production as well as oxidative parameters such as lipid peroxidation and 4-hydroxynonenal levels, whereas GSH and nuclear factor-E2-related factor 2 (Nrf2) levels were decreased. CCl₄ induced profibrogenic mediator expression, hepatic stellate cell (HSC) activation and, consequently, extracellular matrix production. AES exhibited antioxidant, anti-inflammatory and antifibrotic properties, probably because of its capacity to induce Nrf2 expression, reduce NF-κB expression and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis induced by chronic CCl₄ administration.