Antioxidant effects of bis-indole alkaloid indigo and related signaling pathways in the experimental model of Duchenne muscular dystrophy

Cell Stress Chaperones. 2022 Jul;27(4):417-429. doi: 10.1007/s12192-022-01282-0. Epub 2022 Jun 10.

Abstract

Indigo is a bis-indolic alkaloid that has antioxidant and anti-inflammatory effects reported in literature and is a promissory compound for treating chronic inflammatory diseases. This fact prompted to investigate the effects of this alkaloid in the experimental model of Duchenne muscular dystrophy. The main aim of this study was to evaluate the potential role of the indigo on oxidative stress and related signaling pathways in primary skeletal muscle cell cultures and in the diaphragm muscle from mdx mice. The MTT and Neutral Red assays showed no indigo dose-dependent toxicities in mdx muscle cells at concentrations analyzed (3.12, 6.25, 12.50, and 25.00 μg/mL). Antioxidant effect of indigo, in mdx muscle cells and diaphragm muscle, was demonstrated by reduction in 4-HNE content, H2O2 levels, DHE reaction, and lipofuscin granules. A significant decrease in the inflammatory process was identified by a reduction on TNF and NF-κB levels, on inflammatory area, and on macrophage infiltration in the dystrophic sample, after indigo treatment. Upregulation of PGC-1α and SIRT1 in dystrophic muscle cells treated with indigo was also observed. These results suggest the potential of indigo as a therapeutic agent for muscular dystrophy, through their action anti-inflammatory, antioxidant, and modulator of SIRT1/PGC-1α pathway.

Keywords: Activators mitochondrial biogenesis; Indigo; Inflammatory process; Oxidative stress; mdx mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / metabolism
  • Disease Models, Animal
  • Hydrogen Peroxide / metabolism
  • Indigo Carmine / metabolism
  • Indigo Carmine / pharmacology
  • Indigo Carmine / therapeutic use
  • Indole Alkaloids / metabolism
  • Indole Alkaloids / pharmacology
  • Indole Alkaloids / therapeutic use
  • Mice
  • Mice, Inbred mdx
  • Models, Theoretical
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne* / drug therapy
  • Signal Transduction
  • Sirtuin 1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Indole Alkaloids
  • Hydrogen Peroxide
  • Indigo Carmine
  • Sirtuin 1