柚皮素同hPPARs的亲和力与内在活性研究

Study on Affinity of Naringenin with hPPARs and Its Intrinsic Activity

目的:测定柚皮素同过氧化物酶体增殖物激活受体(hPPARs)的亲和力与内在活性,确定柚皮素是否为hPPARs的天然配体。方法:采取放射性标记配基结合试验(RBCA)鉴定柚皮素与hPPARs LBD的配体结合功能,并采用反式激活报道基因试验测定筛出柚皮素的功能活性。结果:RBCA法测得柚皮素与hPPARα的半数抑制率(IC50)为(2.11±0.35)μmol·L-1,抑制常数(Ki)为0.47μmol·L-1;反式激活报道基因试验测得柚皮素对hPPARα、hPPARβ/δ的半数有效剂量(EC50)和最大活性倍数(Emax)分别为11.4μmol·L-1、18.1,对hPPARγ1的EC50和Emax分别为10.3μmol·L-1、16.4。结论:柚皮素能与hPPARs结合,对hPPARα、hPPARγ1、hPPARβ/δ有一定程度的内在活性,是hPPARs的天然配体。

OBJECTIVE： To detect the affinity between naringenin and hPPARs, and to confirm whether narigenin is natural li- gands of hPPARs or not. METHODS： Receptor-ligand binding function were identified by the classical radioligand binding competi- tion assays （RCBA）. The activation function of naringenin was determined through trans-activation reporter gene assays. RE- SULTS： IC50 of naringenin and hPPARα were （2.11 ＋0.35）μmol.L^-1 and the Ki was 0.47 μmol.L^-1 in RBCA; trans-activation re- porter gene assays displayed that hPPARα and hPPARβ/δ were activated potently by naringenin （EC50= 11.4 μmol. L^-1, Emax= 18.1）, and hPPARγ1 was activated by naringenin （EC50=10.3 μmol.L^-1, Emax=16.4）. CONCLUSION： hPPARα,hPPARγ1 ,hP- PARβ/δ can be activated by naringenin and hPPARs, the naringen is the natural ligands of hPPARs.