Hepatoprotective mechanism of Lygodium microphyllum (Cav.) R.Br. through ultrastructural signaling prevention against carbon tetrachloride (CCl4)-mediated oxidative stress

Biomed Pharmacother. 2017 Aug:92:1010-1022. doi: 10.1016/j.biopha.2017.06.014. Epub 2017 Jun 9.

Abstract

Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65μg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.

Keywords: Electron microscopy; Immunohistochemistry; Lygodium microphyllum; Oxidative stress; Pro-inflammatory cytokines.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Alanine Transaminase / blood
  • Aldehydes / metabolism
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Aspartate Aminotransferases / blood
  • Biphenyl Compounds / chemistry
  • Carbon Tetrachloride*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytokines / metabolism
  • Cytoprotection
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ferns / chemistry
  • Inflammation Mediators / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / ultrastructure
  • Male
  • Malondialdehyde / metabolism
  • Microscopy, Electron, Transmission
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Picrates / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • Aldehydes
  • Antioxidants
  • Biphenyl Compounds
  • Cytokines
  • Inflammation Mediators
  • Picrates
  • Plant Extracts
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • Carbon Tetrachloride
  • 1,1-diphenyl-2-picrylhydrazyl
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Deoxyguanosine
  • 4-hydroxy-2-nonenal