Study on the Anti-Inflammatory Activity of Chondroitin Sulfate-Curcumin Amphiphilic Polymers

利用姜黄素中的羟基(-OH)与硫酸软骨素中的羧基(-COOH)发生酯化反应，制备硫酸软骨素–姜黄素(CSC)两亲性聚合物。通过细胞摄取、细胞活性氧(ROS)清除能力、细胞炎症模型测定了CSC的体外活性；测定了CSC对骨关节炎大鼠血清中的IL-1β、TNF-α与PG-E2炎症因子的抑制效果以及体内抗氧化活性。体外活性实验结果表明：CSC在CT-26细胞中的摄取效果、活性氧(ROS)清除能力的清除能力以及对脂多糖诱导RAW264.7细胞验证模型中IL-1β、TNF-α与PG-E2的抑制效果优于硫酸软骨素、姜黄素以及物理混合物。体内活性实验结果表明：CSC对骨关节炎大鼠血清中的IL-1β、TNF-α与PG-E2炎症因子的抑制效果显著优于硫酸软骨素、姜黄素与物理混合物，稍弱于阳性药地塞米松；CSC对GSH和SOD的促进效果均显著优于硫酸软骨素、姜黄素以及物理混合物，稍弱于阳性药双醋瑞因。CSC同时提高了硫酸软骨素与姜黄素的抗炎、抗氧化活性，为解决硫酸软骨素与姜黄素的应用难题提供了良好的解决思路与实验基础，开发前景广阔。Chondroitin sulfate-curcumin (CSC) amphiphilic polymer was prepared by the esterification reaction of the hydroxyl group (-OH) in curcumin and the carboxyl group (-COOH) in chondroitin sulfate. The in vitro activity of CSC was determined through cell uptake, cellular reactive oxygen species (ROS) clearance ability and anti-inflammatory activity ability. The inhibitory effect of CSC on inflammatory factors IL-1β, TNF-α and PG-E2 in the serum of rats with osteoarthritis and its antioxidant activity in vivo were determined. The results of the in vitro activity experiment show that: The uptake effect of CSC in CT-26 cells, the scavenging ability of reactive oxygen species (ROS), and the inhibitory effect on IL-1β, TNF-α and PG-E2 in the validation model of liposolysaccharide induced RAW264.7 cells are superior to those of chondroitin sulfate, curcumin and physical mixtures. The results of in vivo activity experiments indicated that the inhibitory effect of CSC on the inflammatory factors IL-1β, TNF-α and PG-E2 in the serum of rats with osteoarthritis was significantly better than that of chondroitin sulfate, curcumin and physical mixtures, and slightly weaker than that of the positive drug dexamethasone. The promoting effect of CSC on GSH and SOD were significantly better than those of chondroitin sulfate, curcumin and the physical mixture, and slightly weaker than the positive drug diacetoin. CSC simultaneously enhances the anti-inflammatory and antioxidant activities of chondroitin sulfate and curcumin, providing a good solution idea and experimental basis for solving the application problems of chondroitin sulfate and curcumin, and has broad development prospects.