Mulberry leaves extract ameliorates alcohol-induced liver damages through reduction of acetaldehyde toxicity and inhibition of apoptosis caused by oxidative stress signals

Int J Med Sci. 2021 Jan 1;18(1):53-64. doi: 10.7150/ijms.50174. eCollection 2021.

Abstract

Mulberry leaves (Morus alba L.), which are traditional Chinese herbs, exert several biological functions, such as antioxidant, anti-inflammation, antidiabetic, and antitumor. Alcohol intake increases inflammation and oxidative stress, and this increase causes liver injury and leads to liver steatosis, cirrhosis, and hepatocellular carcinoma, which are major health problems worldwide. Previous report indicated that mulberry leaf extract (MLE) exited hepatoprotection effects against chronic alcohol-induced liver damages. In this present study, we investigated the effects of MLE on acute alcohol and liver injury induced by its metabolized compound called acetaldehyde (ACE) by using in vivo and in vitro models. Administration of MLE reversed acute alcohol-induced liver damages, increased acetaldehyde (ACE) level, and decreased aldehyde dehydrogenase activity in a dose-dependent manner. Acute alcohol exposure-induced leukocyte infiltration and pro-inflammation factors, including cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were blocked by MLE in proportion to MLE concentration. MLE prevented alcohol-induced liver apoptosis via enhanced caveolin-1 expression and attenuated EGFR/STAT3/iNOS pathway using immunohistochemical analysis. ACE induced proteins, such as iNOS, COX-2, TNF-α, and IL-6, and inhibited superoxide dismutase expression, whereas co-treated with MLE reversed these proteins expression. MLE also recovered alcohol-induced apoptosis in cultured Hep G2 cells. Overall, our findings indicated that MLE ameliorated acute alcohol-induced liver damages by reducing ACE toxicity and inhibiting apoptosis caused by oxidative stress signals. Our results implied that MLE might be a potential agent for treating alcohol liver disease.

Keywords: acetaldehyde; alcohol liver disease; apoptosis; inflammation; mulberry leaf extract; oxidative stress.

MeSH terms

  • Acetaldehyde / metabolism
  • Acetaldehyde / toxicity*
  • Aldehyde Dehydrogenase / antagonists & inhibitors
  • Aldehyde Dehydrogenase / metabolism
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / isolation & purification
  • Apoptosis / drug effects
  • Disease Models, Animal
  • Enzyme Assays
  • Ethanol / administration & dosage
  • Ethanol / adverse effects
  • Ethanol / metabolism
  • Hep G2 Cells
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Liver Diseases, Alcoholic / drug therapy*
  • Liver Diseases, Alcoholic / etiology
  • Liver Diseases, Alcoholic / pathology
  • Mice
  • Mice, Inbred ICR
  • Morus / chemistry*
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage*
  • Plant Extracts / isolation & purification
  • Plant Leaves / chemistry
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Plant Extracts
  • Reactive Oxygen Species
  • Ethanol
  • Aldehyde Dehydrogenase
  • Acetaldehyde