基于抗氧化剂协同作用的姜黄素高效低毒给药新策略及机制研究

Substantial studies have shown that curcumin reduces the risks of colon cancer. However, curcumin has a poor bioavailability because of its low stability. Therefore high doses of curcumin are needed to exert its health-promoting effects, which may cause severe adverse effects. This project puts forward that co-administration of antioxidant (such as Vitamin C) enhances curcumin bioavailability, leading to a promotion of curcumin effects of anti-colon cancer. We will employ the HPLC-MS techniques to study the mechanism that co-administration of antioxidant enhances curcumin stability in vivo; Also, we will investigate the extent to which antioxidant enhances the anti-cancer effect of curcumin in azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced colon cancer model. This may provide a new approach to enhance bioavailability and biological activity of curcumin, which is of critical importance to develop safe and effective strategies for prevention of colon cancer. What’s more, successful accomplishment of this project may also provide a new insight into the development of new strategies for disease prevention.

姜黄素在防治结直肠癌方面有较好的应用前景，但由于生物稳定性差导致用药浓度高且副作用大，限制了姜黄素的进一步广泛应用。申请人团队前期在体外研究中发现抗氧化剂可通过提高姜黄素生物稳定性增强其生物活性，但其体内作用效果和机制尚不明确。本项目拟构建结直肠癌小鼠模型，采用液相色谱-质谱技术研究维生素C等抗氧化剂增强姜黄素生物稳定性的体内机制；通过动物模型探讨维生素C等抗氧化剂对姜黄素抗结直肠癌的疗效影响；借助分子生物学手段明确维生素C等抗氧化剂增强姜黄素生物活性的分子机制，建立基于抗氧化剂协同作用的姜黄素高生物活性给药新策略，实现姜黄素高效低毒给药。该研究可拓展姜黄素的临床应用范围，对结直肠癌的防治具有重要意义，有望为其他重大疾病防治提供借鉴。

姜黄素在防治结直肠癌方面有较好的应用前景，但由于其生物稳定性差导致用药浓度高且副作用大，限制了姜黄素的进一步广泛应用。申请人团队前期在体外研究中发现抗氧化剂可通过提高姜黄素生物稳定性增强其生物活性，但其体内作用效果和机制尚不明确。本项目利用大鼠药物代谢模型，采用液相色谱-质谱技术发现维生素C等抗氧化剂可增强姜黄素体内生物稳定性；通过氧化偶氮甲烷-葡聚糖硫酸钠联用诱导的小鼠结直肠癌模型揭示了维生素C等抗氧化剂可增强姜黄素抗结直肠癌的疗效影响；借助分子生物学手段明确姜黄素抗肿瘤的体内分子机制；姜黄素通过抑制结直肠肿瘤中标志信号通路Wnt中关键靶蛋白Axin2的表达，降低结直肠肿瘤中炎性因子和促肿瘤因子的表达，发挥抗炎抗肿瘤疗效。本项目建立了基于抗氧化剂协同作用的姜黄素高生物活性给药新策略，实现姜黄素高效低毒给药。该项目揭示了维生素C等抗氧化剂可通过增强姜黄素生物稳定性促进姜黄素的抗肿瘤效果，可拓展姜黄素的临床应用范围，对结直肠癌的防治具有重要意义，有望为其他重大疾病防治提供借鉴。