Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

Abstract

The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases.

Rebaudioside A administration prevents experimental liver fibrosis: an in vivo and in vitro study of the mechanisms of action involved

“…Several studies have demonstrated the pharmacological properties of Stevia rebaudiana Bertoni as a hepatoprotector and mainly as an antifibrotic agent (Ramos‐Tovar, Buendia‐Montaño, et al, ; Ramos‐Tovar, Flores‐Beltrán, et al, ; Ramos‐Tovar, Hernández‐Aquino, et al, ). However, few studies have been performed to evaluate the related pharmacological effects of its secondary compounds, such as Reb A (Holvoet et al, ; Wang et al, ).…”

“…Brown staining of proteins on the tissue was considered a positive reaction. Digital images of the histological sections were collected, and a positive signal was quantified by using ImageJ ® software (NIH, MD, USA) (Ramos‐Tovar, Hernández‐Aquino, et al, ). Appropiate controls to prove the specificity of primary antibodies have been performed by other authors (Eissa, Kenawy, El‐Karef, Elsherbiny, & El‐Mihi, ).…”

“…A standard curve of the cycle threshold ( C T ) values versus the logarithm of the dilution was constructed, and the equation was calculated. The relative expression data were extrapolated from the standard curve (Ramos‐Tovar, Hernández‐Aquino, et al, ). The utilized probes for quantitative PCR amplification are shown in Table .…”

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

“…In this regard, Stevia rebaudiana (stevia), which is a small perennial shrub from Paraguay, has exhibited important antioxidant and anti‐inflammatory properties that suggest that this plant can be an effective antifibrotic and anticirrhotic remedy (Ramos‐Tovar & Muriel, ). Our previous report shows that stevia upregulates Nrf2, which counteracts oxidative stress, and prevents inflammation by inhibiting NF‐κB in CCl 4 ‐cirrhotic rats (Ramos‐Tovar et al, ). However, the effects of stevia on liver fibrogenesis remain unstudied.…”

“…Several medicinal plants have been extensively used in the traditional system of medicine for the management of liver diseases. Because cirrhosis is a major health problem throughout the world, and due to the lack of effective treatments, several studies have suggested that the use of medicinal herbs and phytochemicals could protect against liver damage by several mechanisms, such as the inhibition of oxidative damage, inflammation, and fibrogenesis (Casas‐Grajales et al, ; Hernández‐Aquino et al, ; Ramos‐Tovar et al, ). In this regard, Stevia rebaudiana (stevia), which is a small perennial shrub from Paraguay, has exhibited important antioxidant and anti‐inflammatory properties that suggest that this plant can be an effective antifibrotic and anticirrhotic remedy (Ramos‐Tovar & Muriel, ).…”