Methanol extract of Muntingia calabura leaves attenuates CCl4-induced liver injury: possible synergistic action of flavonoids and volatile bioactive compounds on endogenous defence system

Pharm Biol. 2019 Dec;57(1):335-344. doi: 10.1080/13880209.2019.1606836.

Abstract

Context: Muntingia calabura L. (Muntingiaceae) exerts antioxidant and anti-inflammatory activities, thus, it might be a good hepatoprotective agent.

Objective: This study investigates the effect of methanol extract of M. calabura leaves (MMCL) on hepatic antioxidant and anti-inflammatory activities in CCl4-induced hepatotoxic rat.

Materials and methods: Sprague Dawley rats (n = 6) were treated (p.o.) with 10% DMSO (Groups 1 and 2), 50 mg/kg N-acetylcysteine (Group 3) or, 50, 250, or 500 mg/kg MMCL (Groups 4-6) for 7 consecutive days followed by pretreatment (i.p.) with vehicle (Group 1) or 50% CCl4 in olive oil (v/v) (Groups 2-6) on day 7th. Plasma liver enzymes and hepatic antioxidant enzymes and pro-inflammatory cytokines concentrations were measured while liver histopathology was examined.

Results: MMCL, at 500 mg/kg, significantly (p < 0.05) ameliorated CCl4-induced hepatotoxicity by decreasing the plasma level of alanine transaminase (429.1 versus 168.7 U/L) and aspartate transaminase (513.8 versus 438.1 U/L) as well as the tissue level of nitric oxide (62.7 versus 24.1 nmol/g tissue). At 50, 250, or 500 mg/kg, MMCL significantly (p < 0.05) reduced the tumour necrosis factor α (87.8 versus 32.7 pg/mg tissue), interleukin-1β (1474.4 versus 618.3 pg/mg tissue), and interleukin-6 (136.7 versus 30.8 pg/mg tissue) while increased the liver catalase (92.1 versus 114.4 U/g tissue) and superoxide dismutase (3.4 versus 5.5 U/g tissue). Additionally, qualitative phytochemicals analysis showed that MMCL contained gallic acid, ferulic acid, quercetin, and genistein.

Discussion and conclusions: MMCL ability to attenuate CCl4-induced hepatotoxicity could be helpful in the development of hepatoprotective agents with fewer side effects.

Keywords: GCMS; Muntingiaceae; UHPLC-ESI; antioxidant activity; hepatoprotective activity; oxidative stress markers; phytoconstituents; pro-inflammatory mediators.

MeSH terms

  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / metabolism
  • Antioxidants / therapeutic use*
  • Carbon Tetrachloride
  • 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
  • Flavonoids / isolation & purification
  • Flavonoids / therapeutic use*
  • Male
  • Malvales / chemistry*
  • Phytochemicals / isolation & purification
  • Phytochemicals / therapeutic use*
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry
  • Rats, Sprague-Dawley
  • Volatilization

Substances

  • Antioxidants
  • Flavonoids
  • Phytochemicals
  • Plant Extracts
  • Carbon Tetrachloride

Grants and funding

This research was supported by the Research Acculturation Collaborative Effort grant (RACE; Reference no: R/RACE/A07.00/00290A/002/2015/000234), which was awarded by the Universiti Putra Malaysia (UPM), Malaysia.