Hepatoprotective effects of an Acer tegmentosum Maxim extract through antioxidant activity and the regulation of autophagy

J Ethnopharmacol. 2019 Jul 15:239:111912. doi: 10.1016/j.jep.2019.111912. Epub 2019 Apr 25.

Abstract

Ethnopharmacological relevance: Acer tegmentosum Maxim (AT), the East Asian stripe maple, is an herb used to treat liver disease and is approved as a functional food in Korea. AT protects against hepatic disorders, atopic dermatitis, and diabetes mellitus.

Aim of the study: We explored the mechanism of the hepatoprotective effects of AT extract in in vitro and in vivo levels.

Materials and methods: AT extract from Acer tegmentosum Maxim was extracted by hot water. Hepatoprotective effects of AT extract were confirmed using carbon tetrachloride (CCl4)- or alcohol-induced mouse model, and H2O2- or alcohol-induced HepG2 (liver hepatocellular carcinoma cell line) cells by measuring GOT, GPT, TG, and MDA levels. Hematoxylin and eosin (H&E) staining was used to observe the pathological analysis. Cytotoxicity or protective effect of AT extract was confirmed using MTT assay in HepG2 cells. Antioxidant effect of AT extract was measured using DPPH or H2DCFDA assay. Mechanism study of antioxidant and autophagy was carried out using western blotting and immunofluorescence analysis.

Results: AT extract increased the viability of HepG2 cells treated with H2O2 and ethanol, and protected the liver against damage induced by CCl4 and alcohol. The AT extract increased the levels of nuclear respiratory factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The level of microtubule-associated protein light chain 3 (LC3)-Ⅱ, beclin-1, autophagy-related genes (Atg) such as Atg3 and Atg12-5 as markers of autophagy activation was also increased. Moreover, the AT extract increased activation of mitogen-activated protein kinase (MAPK), which regulated autophagy and HO-1.

Conclusion: Therefore, these results indicate that the AT extract has a hepatoprotective effect by increasing antioxidant activity and inducing autophagy.

Keywords: Acer tegmentosum Maxim; Antioxidant; Autophagy; Hepatoprotection; Mitogen-activated protein kinase.

MeSH terms

  • Acer*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Autophagy / drug effects
  • Carbon Tetrachloride
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / pathology
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinases / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Stems
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Plant Extracts
  • Reactive Oxygen Species
  • Carbon Tetrachloride
  • Mitogen-Activated Protein Kinases