An in vitro and in vivo study: Valencene protects cartilage and alleviates the progression of osteoarthritis by anti-oxidative stress and anti-inflammatory effects

  • Int Immunopharmacol. 2023 Aug 1;123:110726. doi: 10.1016/j.intimp.2023.110726.
Sheng Chen  1 ,  Chen Meng  1 ,  Yi He  1 ,  Hanqing Xu  1 ,  Yunkun Qu  1 ,  Yingguang Wang  1 ,  Yunhui Fan  1 ,  Xiaojian Huang  2 ,  Hongbo You  3
Affiliations
  • 1. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • 2. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: [email protected].
  • 3. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: [email protected].
PMID: 37536183 DOI: 10.1016/j.intimp.2023.110726
Abstract

Background: Osteoarthritis (OA) is a heterogeneous disease involving the whole joint. The pathogenesis involves oxidative stress levels and chronic inflammation, and Valencene (VA) has excellent anti-inflammatory and antioxidant stress abilities.

Purpose: The objective was to study the effects of VA therapy on combating oxidative stress and to evaluate the protective effect of chondrocytes to alleviate the progression of OA.

Methods: C57BL6J mouse chondrocytes were used as the primary cells in this study. Mouse chondrocytes were stimulated with IL-1β, and VA was administered in different concentrations. Reactive Oxygen Species (ROS) assay kits, western blotting, cellular immunofluorescence, and scanning microscopy were used to evaluate VA's antioxidant stress mechanism, anti-inflammatory effect, and cartilage protective ability. The mouse arthritis model constructed by destabilization of medial meniscus (DMM) was observed by micro-CT scan and histology after different treatments.

Results: We found that VA can reverse the rise of ROS under IL-1β, the degeneration of the cartilage extracellular matrix, and the production of inflammatory mediators. In terms of mechanism, VA activated NRF2/HO-1/NQO1 pathway, thus enhancing ROS clearance. The phosphorylation of IκBα is inhibited, which further reduces the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. In addition, VA inhibited mitogen-activated protein kinase (MAPK) signaling molecules P-JNK, P-ERK, and P-P38, inhibiting the production of inflammatory mediators and thus inhibiting Aggrecan and Collagen Type II （COL2）degeneration. In vivo, VA reduced DMM-induced osteophytes and spurs, suppressed subchondral bone destruction, and reduced articular cartilage erosion.

Conclusion: Our study demonstrated that VA is an effective candidate for OA treatment.

Keywords
Antarthritic; Inflammation; NRF2; Osteoarthritis; ROS; Valencene.
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