Abstract
Glaucocalyxin A (GLA) is a bioactive natural compound with anti-inflammatory activity. Herein, the role of GLA in osteoarthritis (OA) was evaluated. Our results demonstrated that the IL-1β-induced inducible nitric oxide synthase (iNOS) and cyclooygenase-2 (COX-2) expression, two enzymes resulting in the release of nitric oxide (NO) and PGE2, were also prevented by GLA in chondrocytes. Moreover, GLA suppressed inflammatory cytokines production in chondrocytes. In addition, the elevated expressions of MMPs and ADAMTSs and the degradation of aggrecan and collagen II were reversed by GLA in chondrocytes. Furthermore, GLA decreased p-p65 level and suppressed the nuclear p65 accumulation in the nucleus of chondrocytes. Collectively, we concluded that GLA attenuated inflammatory response in chondrocytes via NF-κB pathway. These findings suggested that GLA might become an effective agent for OA treatment.
Highlights
Osteoarthritis (OA) is a frequent inflammation-related disease affecting individuals over 60 years of age [1]
A rapid increase in the nitric oxide (NO) production was observed in IL-1βinduced chondrocytes, and this response was mitigated in the Glaucocalyxin A (GLA)-treated groups (Figure 2(a))
An acute increase in Prostaglandin E2 (PGE2) content was noted in response to induction with IL-1β, while the GLA-treated chondrocytes showed significant mitigation in PGE2 content (Figure 2(b))
Summary
Osteoarthritis (OA) is a frequent inflammation-related disease affecting individuals over 60 years of age [1]. The identification of risk factors and understanding of the pathogenesis are central for selecting targets for OA therapy. It is evident for the role of chronic inflammation in the development of OA [3, 4]. It is increasingly evident that interleukin-1β- (IL-1β-) mediated signaling pathways play central roles in OA pathology [7]. The administration of GLA reduces inflammation and mortality in lipopolysaccharide- (LPS-) induced septic-shock mouse model through regulating NLRP3 inflammasome activation [13]. Treatment with GLA reduces the inflammatory response in hydrogen peroxide- (H2O2)induced smooth muscle cells [15]. Evidence has been building that the inflammatory process in chondrocytes plays crucial role in the joint injury. We examined the effect of GLA on inflammation in chondrocytes
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