Stevia rebaudiana tea prevents experimental cirrhosis via regulation of NF-κB, Nrf2, transforming growth factor beta, Smad7, and hepatic stellate cell activation

Stevia has been shown to prevent oxidative stress and inflammation in carbon tetrachloride-induced cirrhosis models. This study aimed to investigate the ability of an aqueous extract of stevia (AES) to prevent thioacetamide (TAA)-induced cirrhosis in rats and to explore its mechanism of action. Liver cirrhosis was established by administering TAA (200mg/kg by i.p. injections three times a week for 10weeks); AES was administered (100mg/kg by gavage daily) during the TAA treatment. Liver damage and fibrosis were evaluated, and the profibrotic pathways were analyzed by western blotting and immunohistochemistry. TAA increased nuclear factor kappa B (NF-B) and pro-inflammatory cytokine production, as well as the malondialdehyde and 4-hydroxynonenal levels, whereas the glutathione/glutathione disulfide and nuclear factor-E2-related factor 2 (Nrf2) levels were decreased. Moreover, TAA increased collagen production, hepatic stellate cell (HSC) activation, and expression of profibrogenic mediators. TAA-treated rats that had been exposed to Mn2+ exhibited altered striatal dopamine turnover, indicating hepatic encephalopathy. AES partially or completely prevented all of these effects. AES showed antioxidant, anti-inflammatory, and antifibrotic properties, probably because of its capacity to induce Nrf2 expression, reduce NF-B expression, and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis and dopamine turnover.