KNOTUS Co., Ltd. Research and Development Center, 189 Donggureung-Ro, Guri-Si 11910, Gyeonggi-Do, Korea.
Kolmar BNH Co., Ltd. 22-15, Sandan-gil, Jeonui-myeon, Sejong-si 30003, Korea.
Nutrients. 2018 Mar 15;10(3):356. doi: 10.3390/nu10030356.
The aim of this study was to investigate the chondroprotective effect of a standardized extract (KBH-JP-040) of the Korean traditional herbs Castor-Aralia, (Bull.) Persoon, and Schischkin on in vivo and in vitro osteoarthritis (OA) models. Cultured rat chondrocytes were pre-treated with KBH-JP-040 (50, 100 and 200 μg/mL) for 1 h, then recombinant human IL-1α (rhIL-1α) for 24 h. For the in vivo model, rabbits ( = 60) were equally divided into experimental groups: normal control (NC), a collagenase-induced OA group, and OA groups treated with KBH-JP-040 (75, 100, and 150 mg/kg body weight) and celecoxib (Cx, 100 mg/kg) orally for 28 days. Treatment with KBH-JP-040 significantly attenuated inflammatory cytokines and matrix metalloproteinases (MMPs), suppressed the expression of IκBα, NF-κB, and JNK/p38 mitogen-activated protein (MAP) kinase, and upregulated aggrecan and collagen type-II expression in rhIL-1α-stimulated chondrocytes. Furthermore, the serum and synovial levels of inflammatory cytokines of rabbits also decreased in the treatment groups when compared with the OA group. Improved magnetic resonance imaging and histopathological findings further confirmed the therapeutic efficacy of KBH-JP-040 against OA. In conclusion, these results indicate that KBH-JP-040 possesses chondroprotective effects, suppressing inflammation and MMPs, and downregulating IκBα, NF-κB, and JNK/p38 MAP kinase-signaling pathways. This might be a potential therapeutic candidate for OA treatment.
本研究旨在探讨一种标准化提取物(KBH-JP-040)对体内和体外骨关节炎(OA)模型的软骨保护作用。培养的大鼠软骨细胞先用 KBH-JP-040(50、100 和 200μg/ml)预处理 1 小时,然后用重组人白细胞介素-1α(rhIL-1α)处理 24 小时。在体内模型中,将兔子(n=60)平均分为实验组:正常对照组(NC)、胶原酶诱导的 OA 组、KBH-JP-040(75、100 和 150mg/kg 体重)和塞来昔布(Cx,100mg/kg)口服治疗的 OA 组,共 28 天。KBH-JP-040 治疗可显著减轻炎症细胞因子和基质金属蛋白酶(MMPs)的表达,抑制 IκBα、NF-κB 和 JNK/p38 丝裂原激活蛋白(MAP)激酶的表达,并上调 rhIL-1α刺激的软骨细胞中聚集蛋白聚糖和 II 型胶原的表达。此外,与 OA 组相比,治疗组兔子血清和滑膜中炎症细胞因子的水平也降低了。改善的磁共振成像和组织病理学发现进一步证实了 KBH-JP-040 对 OA 的治疗效果。总之,这些结果表明,KBH-JP-040 具有软骨保护作用,可抑制炎症和 MMPs,并下调 IκBα、NF-κB 和 JNK/p38 MAP 激酶信号通路。这可能是 OA 治疗的一种潜在治疗候选药物。