基于异相融合反应法从西南特产三种火棘果实中筛选脂溶性酪氨酸酶抑制剂

Tyrosinase inhibitors are clinically used in the treatment of pigmentation disorders. However, due to its unwanted side-effects, research for new alternatives with enhanced therapeutic effects and fewer side-effects are necessary. So far, the tyrosinase is easily soluble in water resulting in the water system for screening tyrosinase inhibitors. So the in vitro screening system is not suitable for screening the fat soluble molecules absorbed well by the skin.Through the early research, our research group found that the extract of Pyracantha fortuneana fruits had good inhibitory effect on tyrosinase. In order to reveal the active components of P. fortuneana fruits, and to look for safe and effective drug in the treatment of pigmentation disorders, this project will isolate tyrosinase inhibitors from rich three species of Pyracantha resources in southwest of China, guided by a novel in vitro screening system; and will reveal the correlation between structure and activity; Finally, will confirme that efficacy of the active ingredients of Pyracantha fruits through in vitro cell experiments and animal experiments. The complete implementation of the project can be to find effective non-toxic tyrosinase inhibitors provide new materials, and provide scientific basis for theirs fruit resources in southwest of China of application in medical care, but also for the Pyracantha fruit resources in southwest of China for the high value utilization has opened up new avenues.

酪氨酸酶抑制剂，是治疗色素沉着性疾病的重要药物，但目前临床用药存在毒副作用大等限制。由于酪氨酸酶的溶解性及酶活等问题局限了其反应体系为水溶性体系，而在水体系里面筛选脂溶性成分比较困难，因此目前的体外筛选体系不适合皮肤更易吸收的脂溶性小分子的筛选。课题组经过前期研究，发现了火棘果提取物的乙酸乙酯部位对酪氨酸酶有较好的抑制作用。为了揭示火棘果中脂溶性活性成分抑制酪氨酸酶的物质基础，寻找安全有效的脂溶性酪氨酸酶抑制剂，本项目拟建立一个基于异相融合反应法的新型脂溶性酪氨酸酶抑制剂体外筛选模型，并以此进行活性跟踪，采用现代分离纯化技术，从西南地区丰富的三种火棘资源中，筛选安全有效的脂溶性酪氨酸酶抑制剂，揭示化学成分结构与活性的相关性；并且通过体外细胞实验与动物实验进一步验证其功效。该项目的实施与完成可以为寻找安全高效的酪氨酸酶抑制剂提供新的材料，为西南地区火棘果资源在医药保健方面的应用提供科学依据。

本课题建立新型脂溶性酪氨酸酶抑制剂体外筛选模型，以酪氨酸酶抑制活性为指导，对西南地区特产的三种火棘果实提取物的脂溶性部位进行系统化学成分研究，分离得到活性脂溶性小分子成分或者部位，然后通过细胞实验筛选和动物实验，研究所得到活性脂溶性小分子成分或者部位的美白功效。.本项目共筛选到5个活性小分子和4个量大化合物。以熊果苷为阳性对照，进行了体内外酪氨酸酶抑制活性研究和初步美白功效研究。从生物活性测试结果可以看出，火棘果活性组分美白面霜可能用于预防和治疗黑色素代谢异常的皮肤或疾病。.本项目首次完成了从三种西南特产的火棘果中快速筛选酪氨酸酶抑制剂。本结果可以为探寻安全、高效的酪氨酸抑制剂，开发新的美白产品提供实验依据。