Hong Jeong-Min, Shin Jun-Kyu, Kim Jeom-Yong, Jang Min-Jung, Park Sun-Kyu, Lee Jong-Hoon, Choi Jung-Hyo, Lee Sun-Mee
School of Pharmacy, Sungkyunkwan University.
GREENCROSS WellBeing Corporation, Research Institute.
Biol Pharm Bull. 2018 Aug 1;41(8):1257-1268. doi: 10.1248/bpb.b18-00207. Epub 2018 May 23.
Chrysanthemum zawadskii var. latilobum (CZ) has been used as a traditional medicine in Asian countries for the treatment of inflammatory diseases. Recently, CZ extract was shown to inhibit differentiation of osteoclasts and provide protection against rheumatoid arthritis. The aim of this study was to investigate the molecular mechanisms of BST106, the ethanol extract of CZ, for cartilage protection in monosodium iodoacetate (MIA)-induced osteoarthritis (OA), particularly focusing on apoptosis and autophagy. BST106 (50, 100, and 200 mg/kg) was orally administered once daily to MIA-induced OA rats. Swelling, limping, roentgenography, and histomorphological changes were assessed 28 d after MIA injection. Biochemical parameters for matrix metalloproteinase (MMP), apoptosis, and autophagy were also assessed. BST106 ameliorated the severity of swelling and limping after MIA injection. Roentgenographic and histomorphological examinations revealed that BST106 reduced MIA-induced cartilage damage. BST106 decreased MIA-induced increases in MMP-2 and MMP-13 mRNA levels. Increased levels of serum cartilage oligomeric matrix protein and glycosaminoglycan release were attenuated by BST106. Furthermore, BST106 suppressed the protein expression of proapoptotic molecules and increased the protein expression of autophagosome- and autolysosome-related molecules. These findings indicate that BST106 protects against OA-induced cartilage damage by inhibition of the apoptotic pathway and restoration of impaired autophagic flux.
宽叶菊（Chrysanthemum zawadskii var. latilobum，CZ）在亚洲国家一直被用作治疗炎症性疾病的传统药物。最近，研究表明CZ提取物可抑制破骨细胞分化，并对类风湿性关节炎具有保护作用。本研究的目的是探讨宽叶菊乙醇提取物BST106在碘乙酸钠（MIA）诱导的骨关节炎（OA）中对软骨保护的分子机制，尤其关注细胞凋亡和自噬。将BST106（50、100和200mg/kg）每日一次口服给予MIA诱导的OA大鼠。在注射MIA后28天评估肿胀、跛行、X线摄影和组织形态学变化。还评估了基质金属蛋白酶（MMP）、细胞凋亡和自噬的生化参数。BST106改善了MIA注射后肿胀和跛行的严重程度。X线摄影和组织形态学检查显示，BST106减轻了MIA诱导的软骨损伤。BST106降低了MIA诱导的MMP-2和MMP-13 mRNA水平升高。BST106减轻了血清软骨寡聚基质蛋白水平升高和糖胺聚糖释放。此外，BST106抑制了促凋亡分子的蛋白表达，并增加了自噬体和自溶酶体相关分子的蛋白表达。这些发现表明，BST106通过抑制凋亡途径和恢复受损的自噬流来保护免受OA诱导的软骨损伤。
