抗糖尿病天然药物的PPARγ活性部位筛选

Screening Active Fractions of Peroxisome Proliferator Activated Receptor γ in Natural Medicines with Potential Antidiabetic Activity

PPARγ是过氧化物酶体增殖物激活受体(PPARs)的其中一个亚型,与糖尿病等代谢疾病在内的慢性疾病密切相关,近年来,PPARγ已成为糖尿病类新药研发的热门靶点。本文利用在He La细胞上构建以PPARγ为靶点的高通量筛选模型,从12种天然药物的58种不同极性提取物中筛选和评价出了对PPARγ具有高活性的8个部位,分别是绿萝花的乙酸乙酯萃取物(EB1)、正己烷提取物(EA)和正丁醇萃取物(EB2),黄连的EB1部分,翼首草的EA、乙醇提取物剩余部分(EB3)和水提物去多糖部分(EC)以及猪牙皂的EB1部分,其最高激活倍数分别相当于阳性对照0.5μg/m L罗格列酮的253%、199%、121%、127%、121%、107%、109%和105%。为开发用于治疗糖尿病及其并发症的新型、安全和高效的天然药物提供了理论和实验依据。

Peroxisome Proliferator-Activated Receptor（ PPAR） γ is one of the subtypes of PPAR,which are closely related to human chronic diseases,such as diabetes mellitus and the other metabolic diseases. In recent years,PPARγ has been as hot target for new drug development in treatment of diabetes area. Therefore,one type of high-throughput screening model for PPARγ was constructed at He La cell in present study,and the 58 different polar extracts from 12 kinds natural medicines were screened using this model. The results showed that Et OAc extract（ EB1）,n-hexane extract（ EA） and n-butyl alcohol extract from Edgeworthia gardneri（ Thymelaeaceae） flower,Et OAc extract（ EB1） from Coptis Chinensis Franch of Sichuan,n-hexane extract（ EA）,supernatant of H2 O extract（ EC） and the remains of Et OH extract（ EB3） from Pterocephalus hookeri（ C. B. Clarke） Hoeck,and Et OAc extract（ EB1） from Fructus Gleditsiae Abnormalis displayed the most remarkable activity for PPARγ,the maximum fold activation of 8 different polarity fractions compared to the positive control（ 0. 5 μg / m L rosiglitazone）,were 253%,199%,121%,127%,121%,109%,107%and 105%,respectively. This study provided the theories and experimental foundation for exploiting the novel,safe and high-efficiency natural medicines for the treatment of diabetes mellitus and its complication.