Research Paper Volume 13, Issue 13 pp 17690—17706
α-Cyperone (CYP) down-regulates NF-κB and MAPKs signaling, attenuating inflammation and extracellular matrix degradation in chondrocytes, to ameliorate osteoarthritis in mice
- 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
- 2 Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, Zhejiang Province, China
- 3 Department of Orthopaedics Surgery, Zhejiang Hospital, Hangzhou 310000, Zhejiang Province, China
- 4 Department of Orthopaedics Surgery, Zhongshan Hospital, Shanghai 200032, China
Received: May 3, 2021 Accepted: June 19, 2021 Published: July 8, 2021https://doi.org/10.18632/aging.203259
How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Inflammation and extracellular matrix (ECM) degradation have been implicated in the pathological process of osteoarthritis (OA). α-Cyperone is the main active component of the traditional Chinese medicine Cyperus rotundus L. In this study, we found that α-Cyperone abolished the IL-1β-induced production of inflammatory cytokines in isolated rat chondrocytes, such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), in a dose-dependent manner (0.75, 1.5 or 3 μM). Also, the results showed that α-Cyperone downregulated the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5), and upregulated the expression of type-2 collagen. Mechanistically, molecular docking tests revealed that α-Cyperone stably and effectively binds to p65, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). α-Cyperone inhibited NF-κB activation by blocking its nuclear transfer, and decreasing the phosphorylation of mitogen-activated protein kinase (MAPKs). In addition, in vivo studies based on a mouse model of arthritis showed that α-Cyperone prevented the development of osteoarthritis. Therefore, α-Cyperone may be a potential anti-OA drug.
ECM: extracellular matrix; OA: osteoarthritis; CYP: α-Cyperone; COX-2: cyclooxygenase-2; TNF-α: tumor necrosis factor alpha; IL-6: interleukin-6; iNOS: nitric oxide synthase; MMPs: metalloproteinases; ADAMTS: thrombospondin motifs; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; MAPKs: mitogen-activated protein kinase; IL-1β: interleukin-1 β; NO: nitric oxide; PGE2: prostaglandin E2; LPS: lipopolysaccharide; NSAIDs: non-steroidal anti-inflammatory drugs; FBS: fetal Bovine Serum; DMM: destabilization of the medial meniscus; qRT-PCR: quantitative real-time polymerase chain reaction; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; DAPI: 4,6-diamidino-2-phenylindole; S-O: safranin O-fast green; OARSI: Osteoarthritis Research Society International.