Okanin alleviates osteoarthritis by suppressing oxidative stress and pyroptosis via Nrf2/HO-1 activation

Di Guo1, Tao Xia1, Dawei Han1

  • 1Orthopedic Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China; Enze Medical Research Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.

Insights

Okanin, a natural flavonoid, protects against osteoarthritis by reducing oxidative stress and cell death. It activates the Nrf2/HO-1 pathway and inhibits NLRP3 inflammasome-mediated pyroptosis, offering a novel treatment strategy for joint disorder.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease.
  • Oxidative stress and NLRP3 inflammasome-mediated pyroptosis contribute to OA.
  • Current OA treatments have limitations.

Purpose of the Study:

  • Investigate Okanin's protective effects in a mouse model of knee osteoarthritis.
  • Elucidate the mechanisms underlying Okanin's chondroprotective action.
  • Explore Okanin as a potential therapeutic agent for OA.

Main Methods:

  • Utilized a destabilization of the medial meniscus (DMM) murine model for OA induction.
  • Assessed Okanin's impact on oxidative stress markers (ROS) and chondrocyte function.
  • Examined the Nrf2/HO-1 and NLRP3 inflammasome/caspase-1/GSDMD pathways.
  • Analyzed articular cartilage morphology and proteoglycan content.

Main Results:

  • Okanin activated the Nrf2/HO-1 pathway, enhancing antioxidant capacity and scavenging ROS.
  • Okanin inhibited NLRP3 inflammasome assembly and caspase-1/GSDMD-dependent pyroptosis.
  • In vivo, Okanin improved cartilage structure, reduced proteoglycan loss, and lowered OARSI scores.
  • Nrf2 was confirmed as a key target of Okanin.

Conclusions:

  • Okanin demonstrates dual chondroprotective effects against oxidative stress and pyroptosis.
  • The Nrf2/HO-1 signaling pathway is crucial for Okanin's mechanism of action.
  • Okanin represents a promising novel therapeutic strategy for osteoarthritis treatment.