Qi-activating quercetin alleviates mitochondrial dysfunction and neuroinflammation in vivo and in vitro

Arch Pharm Res. 2020 May;43(5):553-566. doi: 10.1007/s12272-020-01238-x. Epub 2020 May 25.

Abstract

Parkinson's disease (PD) is a multifactorial neurodegenerative disease manifesting mitochondrial damages and neuroinflammation. Qi is defined as a natural power that can regulate the energy flow in Oriental medicine, whereas mitochondria generate energy power in Western medicine. We investigated whether Qi-enhancing component in Oriental herb medicines could activate mitochondrial activities. Quercetin was found as a major bioactive compound in most Qi-activating Oriental herb medicines through online search for active compounds in several Oriental Medicine databases. We then investigated if quercetin could reverse 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and lipopolysaccharide (LPS)-induced neuroinflammation. Mitochondrial activities were monitored based on complex 1 NADH dehydrogenase activities, ATP contents, mitochondrial membrane potential, cellular/mitochondrial reactive oxygen species, and oxygen consumption rate in SH-SY5Y cells. Quercetin at concentration up to 20 µg/ml was not cytotoxic to SH-SY5Y cells. Pre-treatment with quercetin significantly protected mitochondrial damages in 1 mM MPP+- or 100 ng/ml LPS-treated cells. Quercetin increased expression levels of tyrosine hydroxylase and mitochondria controlling proteins. When in vivo effects of quercetin were assessed by immunohistochemical staining of tissue sections from LPS-injected mice brains, quercetin reduced the activation of microglia and astrocytes in the hippocampus and substantia nigra of LPS-injected mice. Our data suggest that Qi-activating quercetin might be therapeutically effective for neuroinflammation-mediated neurodegeneration by alleviating mitochondrial damages.

Keywords: Herbal medicine; Mitochondria; Neuroinflammation; Parkinson’s disease; Qi-activation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • In Vitro Techniques
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Injections, Intraperitoneal
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Qi*
  • Quercetin / administration & dosage
  • Quercetin / pharmacology*
  • Structure-Activity Relationship
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Tumor Cells, Cultured

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Quercetin