2. Academic Validation
  3. PD184352 exerts anti-inflammatory and antioxidant effects by promoting activation of the Nrf2/HO-1 axis

PD184352 exerts anti-inflammatory and antioxidant effects by promoting activation of the Nrf2/HO-1 axis

  • Biochem Pharmacol. 2023 Apr 6;211:115542. doi: 10.1016/j.bcp.2023.115542.
Xiaohang Zheng 1,  Jianxin Qiu 1,  Han Zhang 1,  Ning Gao 2,  Ting Jiang 1,  Yuhang Gong 1,  Weikang Zhang 1,  Ze Li 1,  Xingbing Feng 3,  Zhenghua Hong 4
Affiliations

Affiliations

  • 1 Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China; Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China.
  • 2 Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China; Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China. Electronic address: Feng714xb@163.com.
  • 4 Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China; Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China. Electronic address: 0001hzh@163.com.
PMID: 37028460 DOI: 10.1016/j.bcp.2023.115542
Abstract

Osteoarthritis (OA) is a disabling joint disease characterized by cartilage degeneration. Reactive Oxygen Species (ROS)-induced oxidative stress is an important cause of early chondrocyte death. For this reason, we investigated PD184352, a small molecule inhibitor with potential anti-inflammatory and antioxidant activity. We evaluated the protective effect of PD184352 against destabilized medial meniscus (DMM)-induced OA in mice. The knee joints of the PD184352-treated group had higher Nrf2 expression and milder cartilage damage. Moreover, in in vitro experiments, PD184352 suppressed IL-1β-induced NO, iNOS, PGE2 production, and attenuated Pyroptosis. PD184352 treatment promoted antioxidant protein expression and reduced the accumulation of ROS by activating the Nrf2/HO-1 axis. Finally, the anti-inflammatory and antioxidant effects of PD184352 were shown to be partially dependent on Nrf2 activation. Our study reveals the potential role of PD184352 as an antioxidant and provides a new strategy for OA treatment.

Keywords

Inflammation; Osteoarthritis; Oxidative stress; PD184352; Pyroptosis.

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