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Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route

Ko-Ta Chen1, Chi-Tai Yeh2,3, Vijesh Kumar Yadav2

  • 1Department of Orthopedics, Taipei Medical University Hospital, Taipei, 11031, Taiwan.

Heliyon
|March 27, 2024
PubMed
Abstract

Insights

Notopterol, derived from a traditional Chinese herb, protects cartilage cells from inflammation and pyroptosis, offering a promising new treatment for osteoarthritis (OA). This compound also reduced OA severity in mice, demonstrating its therapeutic potential.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Immunology

Background:

  • Osteoarthritis (OA) is a prevalent degenerative joint disease affecting millions worldwide, with limited therapeutic options.
  • Current management of OA is challenging due to the lack of a complete cure.
  • Traditional Chinese medicine, including herbs like *Notopterygium incisum*, offers potential anti-inflammatory agents for OA.

Purpose of the Study:

  • To investigate the protective effects of notopterol and has-miR-4248 against inflammation-induced damage in chondrocytes.
  • To explore the role of notopterol in regulating inflammasome formation and pyroptosis in an OA model.
  • To assess the therapeutic potential of notopterol in an *in vivo* osteoarthritis model.

Main Methods:

  • Chondrocyte cell lines (C20A4 and C28/12) were exposed to an inflammatory environment.
  • The effects of notopterol on inflammatory markers (IL-18, TNF-alpha), reactive oxygen species (ROS), and signaling pathways (JAK2/STAT3, NF-κB/NLRP3) were analyzed.
  • The modulation of hsa-miR-4282 by notopterol was investigated.
  • *In vivo* studies involved inducing OA in mice and evaluating treatment effects using OARSI scores.

Main Results:

  • Notopterol significantly reduced inflammatory cytokine levels (IL-18, TNF-alpha) and ROS production in inflamed chondrocytes.
  • Notopterol inhibited the JAK2/STAT3 and NF-κB/NLRP3 signaling pathways, thereby protecting chondrocytes from inflammation and pyroptosis.
  • Notopterol treatment upregulated hsa-miR-4282 expression and decreased OARSI scores in OA mice.

Conclusions:

  • Notopterol demonstrates significant chondroprotective effects by mitigating inflammation and pyroptosis.
  • The compound's mechanism involves the modulation of key inflammatory pathways and hsa-miR-4282.
  • Notopterol shows considerable therapeutic potential for osteoarthritis treatment.
Keywords:
Interleukin 1 betaJAK2/NF-κB/hsa-miR-4282 pathwayNLRP3 inflammasomeNotopterolOsteoarthritisPyroptosis

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