Polyphenols from Toona sinensiss Seeds Alleviate Neuroinflammation Induced by 6-Hydroxydopamine Through Suppressing p38 MAPK Signaling Pathway in a Rat Model of Parkinson's Disease

Neurochem Res. 2020 Sep;45(9):2052-2064. doi: 10.1007/s11064-020-03067-2. Epub 2020 Jun 17.

Abstract

Polyphenols from Toona sinensis seeds (PTSS) have demonstrated anti-inflammatory effects in various diseases, while the anti-neuroinflammatory effects still remain to be investigated. We aimed to investigate the effects of PTSS on Parkinson's disease and underlying mechanisms using a rat model. We employed 6-hydroxydopamine (6-OHDA) to male Sprague Dawley (SD) rats and PC12 cells to construct the in vivo and vitro models of PD and dopaminergic (DA) neuron injury, respectively. Cell viability was detected by cell counting kit-8 (CCK-8) assay and protein levels of inflammatory mediators and some p38 MAPK pathway molecules were investigated by immunohistochemistry and Western blot analyses. The results showed that 6-OHDA significantly increased protein levels of inflammatory mediators, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor α (TNF-α), which could be reversed by PTSS through suppressing the p38 MAPK pathway. The anti-inflammatory effects of PTSS were significantly enhanced by the specific p38 inhibitor of SB203580 in vitro. The present work suggests that PTSS can exert anti-inflammatory effects on PD models, which may be attributed to the suppression of p38 MAPK signaling pathway.

Keywords: Neuroinflammation; Parkinson’s disease; Polyphenols from toona sinensis seeds; p38 MAPK.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Astrocytes / drug effects
  • Cyclooxygenase 2 / metabolism
  • Dopaminergic Neurons / drug effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Microglia / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidopamine / toxicity*
  • PC12 Cells
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Polyphenols / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Seeds / chemistry
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Toona / chemistry
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Polyphenols
  • Tumor Necrosis Factor-alpha
  • Oxidopamine
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat