新型草药组合物（OA-F2）可保护胶原酶诱导的骨关节炎大鼠模型中的软骨退化。
New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis.
机构信息
Department of Herbal Biotechnology, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth Deemed University, Pune-Satara road, Pune, 411 043, Maharashtra, India.
出版信息
BMC Complement Altern Med. 2017 Jan 3;17(1):6. doi: 10.1186/s12906-016-1535-9.
BACKGROUND
Prevalence of osteoarthritis (OA) is on rise on the global scale. At present there are no satisfactory pharmacological agents for treating OA. Our previous study showed that Sida cordifolia L. and Zingiber officinale Rosc. had protective effect on cartilage. Here, we describe the effect of OA-F2, a herbal formulation prepared using combination of these two plants in alleviating OA associated symptoms in a rat model of collagenase-induced OA.
METHODS
OA was induced by intra-articular injection of collagenase type II in wistar rats. Diclofenac (10 mg/kg) was used as a reference control. Rats (n = 6) were divided into 6 groups: Healthy control (HC), osteoarthritic control (OAC), diclofenac (DICLO), OA-F2L (135 mg/kg), OA-F2M (270 mg/kg) and OA-F2H (540 mg/kg). The effects of the 20 days treatment were monitored by parameters like knee diameter, paw volume, paw retraction; serum C-reactive protein (CRP), alkaline phosphatase (ALP) and glycosaminoglycan (GAG). Radiography and histopathology of knee joint were also studied. Additionally, gene expression was studied from isolated synovium tissue proving anti-osteoarthritic potential of OA-F2.
RESULTS
Oral administration of OA-F2 has significantly prevented knee swelling compared to OAC; OA-F2 and DICLO, significantly reduced paw volume compared to OAC. Paw latency was remarkably increased by OA-F2 compared to OAC. OA-F2L (-0.670, p < 0.001), M (-0.110, p < 0.05) and H (0.073) has markedly reduced levels of CRP compared to DICLO. OA-F2L (p < 0.05), M (p < 0.001) and H (p < 0.05) significantly reduced ALP levels, compared to DICLO. GAG release in the serum was also significantly lowered in OA-F2 treated group compared to DICLO. Radiological and histopathological observations showed cartilage protection by OA-F2. OA-F2 has upregulated SOD and GPx. Upregulated CAT expression was observed in OA-F2M and H. Considerable down-regulation of expression of MMP-3 and MMP-9 was observed in all the groups. Up-regulation of TIMP-1 was observed in rats treated with OA-F2L, H and DICLO.
CONCLUSION
OA-F2 has shown therapeutic effects in rat model of collagenase induced OA by demonstrating cartilage protection through controlling MMPs and improving anti-oxidant levels in arthritic synovium and is a potent candidate for further drug development and treatment for OA.
背景
全球范围内骨关节炎（OA）的患病率呈上升趋势。目前，尚无治疗 OA 的满意药理学药物。我们之前的研究表明，三叶鬼针草和生姜对软骨具有保护作用。在这里，我们描述了 OA-F2（一种使用这两种植物组合制成的草药配方）在胶原酶诱导的 OA 大鼠模型中缓解 OA 相关症状的作用。
方法
通过关节内注射 II 型胶原酶诱导 OA，Wistar 大鼠。双氯芬酸钠（10mg/kg）用作参考对照。将大鼠（n=6）分为 6 组：健康对照组（HC）、骨关节炎对照组（OAC）、双氯芬酸钠（DICLO）、OA-F2L（135mg/kg）、OA-F2M（270mg/kg）和 OA-F2H（540mg/kg）。通过监测膝关节直径、爪体积、爪回缩等参数来监测 20 天治疗的效果；血清 C 反应蛋白（CRP）、碱性磷酸酶（ALP）和糖胺聚糖（GAG）。还研究了膝关节的放射摄影和组织病理学。此外，还从分离的滑膜组织中研究了基因表达，证明了 OA-F2 的抗骨关节炎潜力。
结果
与 OAC 相比，OA-F2 的口服给药显著预防了膝关节肿胀；与 OAC 相比，OA-F2 和 DICLO 显著降低了爪体积。与 OAC 相比，OA-F2 显着增加了爪潜伏期。与 DICLO 相比，OA-F2L（-0.670，p<0.001）、M（-0.110，p<0.05）和 H（0.073）显着降低了 CRP 水平。与 DICLO 相比，OA-F2L（p<0.05）、M（p<0.001）和 H（p<0.05）显着降低了 ALP 水平。与 DICLO 相比，OA-F2 治疗组的血清 GAG 释放也显着降低。放射学和组织病理学观察显示 OA-F2 对软骨具有保护作用。OA-F2 上调了 SOD 和 GPx。OA-F2M 和 H 观察到 CAT 表达上调。所有组均观察到 MMP-3 和 MMP-9 的表达显着下调。OA-F2L、H 和 DICLO 治疗的大鼠观察到 TIMP-1 上调。
结论
OA-F2 通过控制 MMP 并改善关节炎滑膜中的抗氧化水平，在胶原酶诱导的 OA 大鼠模型中显示出治疗效果，从而保护软骨，是进一步药物开发和 OA 治疗的潜在候选药物。
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