Sanguinarine protects against osteoarthritis by suppressing the expression of catabolic proteases

// Yan Ma 1, 2 , Xuewu Sun 1, 2 , Kangmao Huang 1, 2 , Shuying Shen 2 , Xianfeng Lin 1, 2 , Ziang Xie 1, 2 , Jiying Wang 2 , Shunwu Fan 1, 2 , Jianjun Ma 1, 2 and Xing Zhao 1, 2 1 Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou 310016, China 2 Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China Correspondence to: Xing Zhao, email: hsing78@gmail.com Keywords: sanguinarine, chondrocyte, osteoarthritis, catabolic proteases Received: February 10, 2017      Accepted: March 24, 2017      Published: April 11, 2017 ABSTRACT Inflammatory cytokines play critical roles in the pathogenesis of osteoarthritis. Recent studies have demonstrated that natural active substances can serve as alternative therapeutic agents for the prevention and treatment of osteoarthritis. Sanguinarine, an alkaloid isolated from the roots of Sanguinaria canadensis , is known to have anti-inflammatory properties. The aim of the present study was to investigate the therapeutic effect of Sanguinarine against osteoarthritis. Sanguinarine inhibited interleukin-1β-induced expression of matrix metalloproteinase 1, 3, and 13, and A disintegrin and metalloproteinase with thrombospondin motifs-5 in chondrocytes, which involved the nuclear factor-κB and c-Jun N-terminal kinase signalling pathways. Furthermore, the study of interleukin-1β-induced cartilage matrix degradation in an anterior cruciate ligament transection-induced osteoarthritis model revealed that Sanguinarine ameliorated osteoarthritis by inhibiting the expression of matrix metalloproteinase 1, 3, and 13, and A disintegrin and metalloproteinase with thrombospondin motifs-5. In conclusion, we demonstrated for the first time that Sanguinarine suppressed the expression of matrix metalloproteinase 1, 3, and 13, and A disintegrin and metalloproteinase with thrombospondin motifs-5 in vitro , ex vivo, and in vivo , indicating its potential usefulness in treating osteoarthritis.