Osteoarthritis (OA) is a chronic degenerative and musculoskeletal disorder. The toxicity associated with nonsteroidal antiinflammatory drugs (NSAIDs) limits its use in the management of OA. To ameliorate these toxicities, natural antioxidants can be used as substitutes for the management of OA. Therefore, this study is aimed to investigate the prophylactic mechanisms of Punica granatum L. peel (PGP) in collagenase‐induced OA rat compared with indomethacin. OA was induced in female Sprague Dawley rats by intraarticular injection of collagenase type‐II and treated with PGP (250 and 500 mg/kg body wt) and a positive control (PC) indomethacin (3 mg/kg body wt). The results demonstrated that PGP reduced the collagenase induced OA as compared with indomethacin treated group through reducing blood ALP (P < .001) and significantly (P < .001) inhibited cartilage erosion as indicated in histological slides with retention of collagen and proteoglycan content. Quantitative real‐time PCR analysis revealed the considerable (P < .05) upregulation in the expression of COL‐2 gene and downregulation of MMP‐3 and COX‐2 genes in the PGP treated group. The high phenolic content (633 ± 1.16 mg/GAE) and flavonoid content (420.3 ± 2.14 mg/RE) contribute to the strong antioxidant activity with IC50 value (320 ± 2.2 μg/mL) of DPPH free radical scavenging activity. These results need further validation in clinical studies and thus, PGP could be developed as a preventive drug treatment for OA.

中文翻译：

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石榴皮提取物通过调节 COL ‐2、MMP ‐3 和 COX ‐2 表达对胶原酶诱导的骨关节炎大鼠的抗骨关节炎作用

骨关节炎（OA）是一种慢性退行性肌肉骨骼疾病。非甾体抗炎药 (NSAID) 的相关毒性限制了其在 OA 治疗中的应用。为了减轻这些毒性，天然抗氧化剂可以用作骨关节炎治疗的替代品。因此，本研究旨在探讨石榴皮（PGP）与吲哚美辛相比对胶原酶诱导的 OA 大鼠的预防机制。通过关节内注射 II 型胶原酶在雌性 Sprague Dawley 大鼠中诱导 OA，并用 PGP（250 和 500 mg/kg 体重）和阳性对照 (PC) 吲哚美辛（3 mg/kg 体重）治疗。结果表明，与吲哚美辛治疗组相比，PGP 通过降低血液 ALP (P < .001) 减少胶原酶诱导的 OA，并显着 (P < .001) 抑制软骨侵蚀，如组织学幻灯片所示，保留胶原蛋白和蛋白聚糖含量。实时定量 PCR 分析显示，PGP 治疗组中 COL-2 基因表达显着上调（P < .05），MMP-3 和 COX-2 基因表达下调。高酚含量 (633 ± 1.16 mg/GAE) 和类黄酮含量 (420.3 ± 2.14 mg/RE) 具有很强的抗氧化活性，具有 DPPH 自由基清除活性的 IC50 值 (320 ± 2.2 μg/mL)。这些结果需要在临床研究中进一步验证，因此，PGP 可以开发为 OA 的预防性药物治疗。