Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Food Funct. 2020 Nov 18;11(11):10219-10230. doi: 10.1039/d0fo02192j.
Osteoarthritis is a chronic degenerative disease characterized by cartilage destruction. It is the fourth most disabling disease worldwide and is currently incurable. Inflammation and extracellular matrix (ECM) degradation are considered to be substantial reasons for accelerating the progression of OA. β-Hydroxyisoamylshikonin (β-HIVS) is a natural naphthoquinone compound with anti-inflammatory and antioxidant activity. However, the effect of β-HIVS on OA is still unclear. In this study, we found that β-HIVS can down-regulate the expression of NO, PEG2, IL-6, TNF-α, COX-2, and iNOS, suggesting its anti-inflammatory effects in chondrocytes; we also found that β-HIVS may down-regulate the expression of ADAMTS5 and MMP13 and up-regulate the expression of aggrecan and collagen II to inhibit the degradation of ECM. Mechanistically, β-HIVS inhibited the NFκB pathway by activating the Nrf2/HO-1 axis, thereby exerting its anti-inflammatory and inhibitory effects on ECM degradation. In vivo experiments also proved the therapeutic effects of β-HIVS on OA in mice, and Nrf2 is the target of β-HIVS. These findings indicate that β-HIVS may become a new drug for the treatment of OA.
骨关节炎是一种以软骨破坏为特征的慢性退行性疾病。它是全球第四大致残性疾病，目前尚无治愈方法。炎症和细胞外基质（ECM）降解被认为是加速 OA 进展的重要原因。β-羟基异戊酰紫草素（β-HIVS）是一种具有抗炎和抗氧化活性的天然萘醌化合物。然而，β-HIVS 对 OA 的影响尚不清楚。在这项研究中，我们发现β-HIVS 可以下调软骨细胞中 NO、PEG2、IL-6、TNF-α、COX-2 和 iNOS 的表达，表明其具有抗炎作用；我们还发现，β-HIVS 可能下调 ADAMTS5 和 MMP13 的表达，上调聚集蛋白聚糖和 II 型胶原的表达，从而抑制 ECM 的降解。在机制上，β-HIVS 通过激活 Nrf2/HO-1 轴抑制 NFκB 通路，从而发挥其抗炎和抑制 ECM 降解的作用。体内实验也证明了β-HIVS 对小鼠 OA 的治疗作用，Nrf2 是β-HIVS 的作用靶点。这些发现表明，β-HIVS 可能成为治疗 OA 的一种新药。
