Hepatoprotective effects of Flagellaria indica are mediated through the suppression of pro-inflammatory cytokines and oxidative stress markers in rats

Pharm Biol. 2016 Aug;54(8):1420-33. doi: 10.3109/13880209.2015.1104697. Epub 2016 Jan 25.

Abstract

Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis. Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl4)-mediated liver damage. Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague-Dawley rats once daily for 14 consecutive days at 300, 400, and 500 mg/kg b.w. prior to CCl4 treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Results Total phenolic content in the aqueous extract of FI leaves was 65.88 ± 1.84 mg gallic acid equivalent/g. IC50 value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400 μg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38-74% recovery), and malondialdehyde formation (25-87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8-hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor-α, interleukin-6, prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl4-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500 mg/kg b.w.). Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI.

Keywords: Antioxidant enzymes; electron microscopy; histopathology; immuno-histochemistry.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hydrocarbons, Brominated
  • Immunohistochemistry
  • Inflammation Mediators / metabolism*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / ultrastructure
  • Magnoliopsida
  • Male
  • Microscopy, Electron, Transmission
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Plants, Medicinal
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Hydrocarbons, Brominated
  • Inflammation Mediators
  • Plant Extracts
  • carbon tetrabromide