Protective effect of Terminalia muelleri against carbon tetrachloride-induced hepato and nephro-toxicity in mice and characterization of its bioactive constituents

Pharm Biol. 2016;54(2):303-13. doi: 10.3109/13880209.2015.1035794. Epub 2015 Apr 20.

Abstract

Context: Terminalia is used in folk medicine for the treatment of various diseases.

Objective: The objective of this study is to investigate the hepatonephro protective activity of a polyphenol-rich fraction (TMEF) obtained from Terminalia muelleri Benth. (Combretaceae) against CCl4-induced toxicity in mice.

Materials and methods: TMEF was administered (100, 200, and 400 mg/kg/d) for 5 d. CCl4 was administered at the end of the experiment. Hepatic and renal biomarkers were measured in the serum. Glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were estimated in the liver and kidney tissues. The active constituents of TMEF were identified by HPLC-PDA-ESI/MS/MS.

Results: TMEF is rich in ellagitannins, galloyl esters, phenolic acids, and flavone-C-glucosides. TMEF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT (17, 43, and 53%), AST (20, 46, and 58%), ALP (20, 48, and 56%), LDH (21, 47, and 58%), hepatic MDA (23, 49, and 54%), renal MDA (22, 35, and 52%), creatinine (48, 66, and 91%), uric acid (16, 34, and 59%), urea (22, 39, and 59%), and cholesterol (20, 27, and 46%). Furthermore, TMEF administration significantly (p < 0.001) increased hepatic GSH (15, 51, and 79%), renal GSH (23, 45, and 73%), hepatic SOD (9, 52, and 95%), renal SOD (39, 66, and 85%) and protein levels (17, 24, and 29%) at the tested doses of TMEF, respectively. Pretreatment with TMEF preserved the hepatic architecture and protected from ballooning degeneration, liver necrosis, renal inflammation, and degeneration of the kidney tubules.

Conclusion: TMEF has a marked hepato-nephro protective effect.

Keywords: Antioxidant; ellagitannins; flavone-C-glucosides; glutathione; hepatoprotective; lipid peroxidation; nephroprotective.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Carbon Tetrachloride / toxicity
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Dose-Response Relationship, Drug
  • Kidney Function Tests
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Mice
  • Molecular Structure
  • Nephritis / metabolism
  • Nephritis / pathology
  • Nephritis / prevention & control*
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Plant Extracts / toxicity
  • Plant Leaves / chemistry
  • Polyphenols / isolation & purification
  • Polyphenols / therapeutic use*
  • Polyphenols / toxicity
  • Protective Agents / isolation & purification
  • Protective Agents / therapeutic use*
  • Protective Agents / toxicity
  • Terminalia / chemistry*
  • Toxicity Tests, Acute

Substances

  • Antioxidants
  • Plant Extracts
  • Polyphenols
  • Protective Agents
  • Carbon Tetrachloride