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

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:

• Muntingiaceae
• hepatoprotective activity
• antioxidant activity
• oxidative stress markers
• pro-inflammatory mediators
• phytoconstituents
• UHPLC-ESI
• GCMS

Acknowledgements

The authors thanked the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia for providing the facilities to carry out this research.

Disclosure statement

The authors report no declaration of interest.

Additional information

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.