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

Abstract

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 (200 mg/kg by i.p. injections three times a week for 10 weeks); AES was administered (100 mg/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‐κB) 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‐κB expression, and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis and dopamine turnover.

• Authors: Erika Ramos-Tovar, Rosa E Flores-Beltrán, Silvia Galindo-Gómez, Eunice Vera-Aguilar, Araceli Diaz-Ruiz, Sergio Montes, Javier Camacho, Víctor Tsutsumi, Pablo Muriel
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 32 Issue 12 Pg. 2568-2576 (12 2018) ISSN: 1099-1573 [Electronic] England
• PMID: 30251285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-E2-Related Factor 2
• NF-kappa B
• Plant Extracts
• Smad7 Protein
• Smad7 protein, rat
• Transforming Growth Factor beta
• Thioacetamide

Topics

• Animals
• Hepatic Stellate Cells (drug effects, physiology)
• Liver Cirrhosis, Experimental (chemically induced, prevention & control)
• Male
• NF-E2-Related Factor 2 (physiology)
• NF-kappa B (physiology)
• Plant Extracts (therapeutic use)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Smad7 Protein (physiology)
• Stevia
• Thioacetamide
• Transforming Growth Factor beta (physiology)