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

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.

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Acknowledgements

This research was supported by the Korean Health Technology R&D Project (HI14C2700) through the Korea Health Industry Development Institute (KHIDI) and by the Basic Science Research Program (2018R1A6A1A03025124 and 2020R1A2C1008699) through the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT). The funding source had no role in the collection of data or in the decision to submit this manuscript for publication. Authors thank Hyun Soo Jeon and Hyung Seok Roh for starting the project on Qi and mitochondria when they were students of Korean Minjok Leadership Academy High School, Gangwon-do, Korea.

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Kang, S., Piao, Y., Kang, Y.C. et al. Qi-activating quercetin alleviates mitochondrial dysfunction and neuroinflammation in vivo and in vitro. Arch. Pharm. Res. 43, 553–566 (2020). https://doi.org/10.1007/s12272-020-01238-x

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Keywords

  • Mitochondria
  • Herbal medicine
  • Qi-activation
  • Neuroinflammation
  • Parkinson’s disease