Osteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged. The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats. Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes. HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac. This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract Graphical abstract

中文翻译：

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双氯芬酸与富含芹菜素糖苷的小刺花提取物改善骨质疏松-骨关节炎大鼠模型炎症和分解代谢蛋白酶调节的比较

骨质疏松性骨关节炎是老年人的一种致残性肌肉骨骼疾病。在骨质疏松性骨关节炎大鼠中，比较了双氯芬酸与富含芹菜素-C-糖苷的 Clinacanthus nutans (CN) 叶提取物的抗炎和抗分解代谢作用。雌性 Sprague Dawley 大鼠被随机分为五组 (n = 6)。四组因骨质疏松而切除双侧卵巢，并通过右膝关节关节内注射碘乙酸钠（MIA）诱发骨关节炎。Sham组进行假手术，注射生理盐水和去离子饮用水。治疗组每天口服200或400毫克提取物/公斤体重或5毫克双氯芬酸/公斤体重，持续28天。通过大体和组织学结构、显微 CT 分析、血清蛋白生物标志物以及炎症和分解代谢蛋白酶基因的 mRNA 表达来监测关节软骨和骨的变化。HPLC 分析证实芹菜素-C-糖苷（shaftoside、牡荆素和异牡荆素）是提取物中的主要化合物。该提取物可显着且剂量依赖性地减少软骨侵蚀、骨质流失、软骨分解代谢变化、血清骨质疏松性骨关节炎生物标志物（原胶原II型N末端前肽PIINP；原胶原型IN末端前肽PINP；骨钙素） 、炎症 (IL-1β) 和核因子-κ-β NF-κβ、白细胞介素-1-β IL-1β、环氧合酶-2 的 mRNA 表达；骨质疏松骨关节炎大鼠中的基质金属蛋白酶 13 MMP13 活性与双氯芬酸相当。这项研究表明，400 mg CN 提取物/kg（约 0.2 mg 芹菜素当量/kg）的芹菜素-C-糖苷在抑制炎症和分解代谢蛋白酶以预防骨质疏松性骨关节炎方面与双氯芬酸相当。图形摘要 图形摘要