Isoalantolactone (IAL) Regulates Neuro-Inflammation and Neuronal Apoptosis to Curb Pathology of Parkinson's Disease

Cells. 2022 Sep 19;11(18):2927. doi: 10.3390/cells11182927.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease in which neuronal apoptosis and associated inflammation are involved in its pathogenesis. However, there is still no specific treatment that can stop PD progression. Isoalantolactone (IAL) plays a role in many inflammation-related diseases. However, its effect and mechanism in PD remain unclear. In this study, results showed that IAL administration ameliorated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-related pathological impairment and decreased motor activity in mice. Results from in vitro mechanistic studies showed that IAL regulated apoptosis-related proteins by activating the AKT/Nrf2 pathway, thereby suppressing the apoptosis of SN4741 cells induced by N-methyl-4-phenylpyridinium Iodide (MPP+). On the other hand, IAL inhibited LPS-induced release of pro-inflammatory mediators in BV2 cells by activating the AKT/Nrf2/HO-1 pathway and inhibiting the NF-κB pathway. In addition, IAL protected SN4741 from microglial activation-mediated neurotoxicity. Taken together, these results highlight the beneficial role of IAL as a novel therapy and potential PD drug due to its pharmacological profile.

Keywords: PD; apoptosis; isoalantolactone; neuro-inflammation; neuro-protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects
  • 1-Methyl-4-phenylpyridinium
  • Animals
  • Apoptosis
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Iodides / adverse effects
  • Lipopolysaccharides / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2
  • NF-kappa B / metabolism
  • Neurodegenerative Diseases*
  • Parkinson Disease* / metabolism
  • Proto-Oncogene Proteins c-akt
  • Pyrrolidines
  • Sesquiterpenes

Substances

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Inflammation Mediators
  • Iodides
  • isoalantolactone
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Pyrrolidines
  • Sesquiterpenes

Grants and funding

This work was funded by a Fundamental Research Funds for the Central Universities under grant (project Number. 2021JCKT-06) and by the College Students Innovation and Entrepreneurship Training Program of Jilin University (project Number. 202210183336, 202210183317).