Aging
Navigate
Submit an Article
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

Huawei Zhang1,2, Sunlong Li1,2, Jiajie Lu1,2, Jie Jin1,2, Gaosheng Zhu1,2, Libo Wang1,2, Yingzhao Yan3, Linjie He1,2, Ben Wang4, Xiangyang Wang1,2, Huachen Yu1,2
  • 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
  • 2Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, Zhejiang Province, China
  • 3Department of Orthopaedics Surgery, Zhejiang Hospital, Hangzhou 310000, Zhejiang Province, China
  • 4Department of Orthopaedics Surgery, Zhongshan Hospital, Shanghai 200032, China
* Equal contribution
Received: May 3, 2021Accepted: June 19, 2021Published: July 8, 2021
https://doi.org/10.18632/aging.203259

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.

Abstract

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.