Protective effect of solanesol in glucose-induced hepatocyte injury: Mechanistic insights on oxidative stress and mitochondrial preservation

Chem Biol Interact. 2023 Sep 25:383:110676. doi: 10.1016/j.cbi.2023.110676. Epub 2023 Aug 14.

Abstract

Solanesol is a tetra sesquiterpene enol with various biological activities. Modern medical studies have confirmed that solanesol has the function of lipid antioxidation and scavenges free radicals. This study aimed to investigate the protective effect of solanesol against oxidative damage induced by high glucose on human normal hepatocytes (L-02 cells) and its possible mechanism. The results showed that solanesol could effectively improve the decrease of cell viability induced by high glucose, decrease the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the extracellular medium, increased the enzyme activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), balanced the level of reactive oxygen species (ROS) in cells, inhibited lipid peroxidation of all kinds of biological membranes, and restored mitochondrial membrane potential (MMP). In addition, Solanesol also inhibited the expression of Keap1, promoted the nuclear translocation of Nrf2 by hydrogen bonding with Nrf2, and activated the expression of downstream antioxidant factors NQO1 and HO-1. Altogether, these findings suggest that solanesol may be a potential protectant against diabetic liver injury.

Keywords: Diabetic liver injury; Keap1-Nrf2-ARE pathway; Mitochondrial dysfunction; Oxidative stress; Solanesol.

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Hepatocytes
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress*

Substances

  • solanesol
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Antioxidants