Protection of Ficus pandurata Hance against acute alcohol-induced liver damage in mice via suppressing oxidative stress, inflammation, and apoptosis

J Ethnopharmacol. 2021 Jul 15:275:114140. doi: 10.1016/j.jep.2021.114140. Epub 2021 Apr 27.

Abstract

Ethnopharmacological relevance: Ficus pandurata Hance (FPH) is a traditional Chinese herbal medicine, which is commonly used for liver protection in the folk of Southeast China. However, the medicinal part and pharmacological mechanism have not been clarified yet.

Aim of the study: This study aims to investigate the medicinal part of FPH for liver protection and uncover the potential mechanism.

Materials and methods: Acute alcoholic liver damage (ALD) mice model induced by intragastric administration with 50% alcohol was used to evaluate the liver protection of FPH. Different parts of FPH, including the root (FPHR), stem (FPHS), leaf (FPHL), and whole plant (FPHWP), were selected to investigate the liver-protected efficacy and determine which part is the medicinal part. Acute oral toxicity (AOT) test was performed to determine the acute toxicity of FPH on Kunming mice. The liver-protected effect of FPH was determined by evaluating the liver function, liver morphological changes, and liver pathological changes. The underlying mechanism was investigated by evaluating the effect on oxidative stress, inflammation, and apoptosis in liver tissues via ELISA, H&E staining, Western Blot, and TUNEL staining assays.

Results: In the screening test for medicinal parts of FPH, all of the extracts from FPHR, FPHS, FPHL, and FPHWP could alleviate the acute ALD of mice, including reducing abnormal levels of AST, ALT, and relative liver weight. Especially, the alleviated efficacies of FPHS and FPHL were better than those of FPHWP and FPHR, showing that the aerial part (FPHAP, including the stem and leaf), is probably the medicinal part of FPH against acute ALD. In the AOT test, FPHAP at the maximum administration dosage (480 g/kg, calculated based on the quantity of crude material) did not induce obvious abnormality and death of mice, and had no significant influence on body weight, as well as the relative organ weight, showing that the maximum tolerated dose (MTD) of FPHAP was 480 g/kg on Kunming mice. In the anti-acute ALD study, FPHAP significantly reduced the levels of AST, ALT, LDH, ROS, MDA, TNF-α, IL-1β, IL-18, and IL-6, alleviated the morphology of liver injury, increased the levels of SOD and GSH, up-regulated the expressions of Nrf-2, HO-1 and NQO1, and reduced apoptosis of liver cells in acute ALD mice, indicating that FPHAP could significantly alleviate acute ALD by suppressing oxidative stress, inflammation, and apoptosis.

Conclusions: FPH could protect acute alcohol-induced liver damage of mice by suppressing oxidative stress, inflammation, and apoptosis. Our study provides scientific evidence for the therapeutic effect of Ficus pandurata Hance in acute ALD mice and suggests its potential development in humans for liver protection, supporting its traditional application.

Keywords: Alcoholic liver damage; Apoptosis; Ficus pandurata Hance; Inflammation; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Ethanol / toxicity
  • Female
  • Ficus / chemistry*
  • Heme Oxygenase-1 / metabolism
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Plant Components, Aerial / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Toxicity Tests, Acute

Substances

  • Antioxidants
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Plant Extracts
  • Protective Agents
  • Reactive Oxygen Species
  • Ethanol
  • Heme Oxygenase-1
  • Hmox1 protein, mouse