Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats

Biomed Pharmacother. 2017 Nov;95:1040-1050. doi: 10.1016/j.biopha.2017.08.082. Epub 2017 Sep 13.


Oxidative stress and hepatic inflammatory response is primarily implicated in the pathogenesis of LPS induced acute liver injury. Stevioside, a diterpenoidal glycoside isolated from the Stevia rebaudiana leaves, exerts potent anti-oxidant, anti-inflammatory and immunomodulatory activities. The present study was aimed to investigate the hepatoprotective effect of hydroalcoholic extract of Stevia rebaudiana leaves (STE EXT) and its major phytochemical constituent, stevioside (STE) in LPS induced acute liver injury. The hepatoprotective activity of STE EXT (500mg/kg p.o) and STE (250mg/kg p.o) was investigated in lipopolysaccharide (LPS 5mg/kg i.p.) induced acute liver injury in male wistar rats. Our results revealed that both STE EXT and STE treatment ameliorated LPS induced hepatic oxidative stress, evident from altered levels of reduced SOD, Catalase, GSH, MDA, NO. Histopathological observations revealed that both STE EXT and STE attenuated LPS induced structural changes and hepatocellular apoptosis providing additional evidence for its hepatoprotective effect. Further, STE EXT and STE significantly restored the elevated serum and tissue levels of AST and ALT in LPS treated rats. Furthermore, both STE EXT and STE rescued hepatocellular dysfunctions to normal by altering the level of proinflammatory cytokines such as TNF-α, IL-1β and IL-6 exhibiting its anti-inflammatory potential. In conclusion, both STE EXT and STE demonstrated excellent hepatoprotective effects against endotoxemia induced acute liver injury possibly through suppression of hepatic inflammatory response and oxidative stress, attributing to its medicinal importance in treating various liver ailments.

Keywords: Hepatoprotective; Inflammation; Lipopolysaccharide; Oxidative stress; Stevia rebaudiana; Stevioside.

MeSH terms

  • Acute Disease
  • Animals
  • Biphenyl Compounds / chemistry
  • Chromatography, Thin Layer
  • Cytokines / metabolism
  • Diterpenes, Kaurane / pharmacology*
  • Ethanol / chemistry*
  • Flavonoids / analysis
  • Free Radical Scavengers / pharmacology
  • Glucosides / pharmacology*
  • Inflammation Mediators / metabolism
  • Lipid Peroxidation / drug effects
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / injuries*
  • Liver / pathology
  • Liver / physiopathology
  • Liver Function Tests
  • Male
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Phenols / analysis
  • Phytochemicals / pharmacology
  • Phytotherapy
  • Picrates / chemistry
  • Plant Extracts / pharmacology*
  • Rats, Wistar
  • Stevia / chemistry*
  • Water / chemistry*


  • Biphenyl Compounds
  • Cytokines
  • Diterpenes, Kaurane
  • Flavonoids
  • Free Radical Scavengers
  • Glucosides
  • Inflammation Mediators
  • Lipopolysaccharides
  • Phenols
  • Phytochemicals
  • Picrates
  • Plant Extracts
  • Water
  • stevioside
  • Nitric Oxide
  • Ethanol
  • 1,1-diphenyl-2-picrylhydrazyl