Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis via Regulating the MAPK/NF-κB-Autophagy Pathway

Minjun Yao; Caihua Zhang; Lingzhi Ni; Xiaoxiao Ji; Jianqiao Hong; Yazhou Chen; Jie Wang; Congsun Li; Jiyan Lin; Tingting Lu; Yihao Sheng; Menghao Sun; Mingmin Shi; Chenhe Zhou; Xunzi Cai

doi:10.3389/fphar.2022.854239

Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis via Regulating the MAPK/NF-κB-Autophagy Pathway

Front Pharmacol. 2022 Jun 21:13:854239. doi: 10.3389/fphar.2022.854239. eCollection 2022.

Authors

Minjun Yao^{1

2}, Caihua Zhang³, Lingzhi Ni^{1

4}, Xiaoxiao Ji^{1

2}, Jianqiao Hong^{1

2}, Yazhou Chen^{1

2}, Jie Wang^{1

2}, Congsun Li^{1

2}, Jiyan Lin^{1

2}, Tingting Lu⁵, Yihao Sheng⁶, Menghao Sun^{1

2}, Mingmin Shi^{1

2}, Chenhe Zhou^{1

2}, Xunzi Cai^{1

2}

Affiliations

¹ Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Orthopedic Research Institute of Zhejiang University, Hangzhou, China.
³ Department of Orthopedics, Ningbo First Hospital, Ningbo, China.
⁴ Department of Orthopedics, Hangzhou Third Hospital, Hangzhou, China.
⁵ Department of Oncology, The First Clinical Medical College of Wenzhou Medical University, Wenzhou, China.
⁶ Department of Orthopedics, Hangzhou Xiaoshan Cha Ting Orthopedic Trauma Hospital, Hangzhou, China.

Abstract

Osteoarthritis is a worldwide joint disease caused by abnormal chondrocytic metabolism. However, traditional therapeutic methods aimed at anti-inflammation for early-stage disease are palliative. In the present study, we demonstrated that cepharanthine (CEP), extracted from the plant Stephania cepharantha, exerted protective medicinal efficacy on osteoarthritis for the first time. In our in vitro study, CEP suppressed the elevated expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and inducible nitric oxide synthase (iNOS) stimulated by IL-1β or TNF-α by inhibiting the activation of MAPK and NF-κB signaling pathways, and upregulated the protein expression of aggrecan, collagen II, and Sox9. Also, CEP could reverse the reduced level of cellular autophagy in IL-1β or TNF-α-induced chondrocytes, indicating that the protective effect of CEP on osteoarthritis was achieved by restoring MAPK/NF-κB-mediated autophagy. Furthermore, in a murine OA model, CEP mitigated cartilage degradation and prevented osteoarthritis in the CEP-treated groups versus the OA group. Hence, our results revealed the therapeutic prospect of CEP for anti-osteoarthritic treatment.

Keywords: MAPK; NF-κB; autophagy; cepharanthine; chondrocytes; osteoarthritis.