黄酮类化合物抑制小胶质细胞活化的构效关系研究

Structure-activity Relationships of Flavonoids Suppressing the Activation of Microglia Cells

探讨系列黄酮类化合物抑制脂多糖(LPS)诱导的原代大鼠小胶质细胞激活的构效关系。采用MTT分析法检测细胞存活率;Griess法测定LPS激活的小胶质细胞NO释放的变化。在0.3～30μM浓度范围内,8种黄酮类化合物与LPS联合应用对小胶质细胞存活率无显著影响;黄酮、白杨素、芹菜配基、汉黄芩素、四羟黄酮5种黄酮类化合物可显著抑制LPS激活的小胶质细胞NO产生,而二羟黄酮类3种化合物(二羟黄酮、柚皮素、儿茶素)对细胞NO无显著抑制作用。黄酮类化合物母核结构中C-23,双键可能对抑制小胶质细胞激活很重要,其抑制作用的强弱取决于分子的取代类型。

Objective To evaluate the Structure-activity relationships of flavonoids on NO production in LPS-activated primary rat microglial ceils. Methods The effects of flavonoids on cell viability were evaluated by MTT reduction assay. Nitrite levels in the culture supernatants were examined by Griess assay. Results We found that treatments with flavonoids （0.3 - 30 μM） and 1 μg/ml of LPS had no significant cytotoxicity com- pared with the vehicle control. Flavonoids such as flavone, flavone, apigenin, wogonin and luteolin inhibited NO production, as measured by nitrite formation at 0.3 - 30 μM. In contrast, flavanones, such as flavanone, naringenin and catechin did not demonstrate significant inhibition up to 30 μM. Conclusion These results clearly indicated that a C-2,3 double bond might be important, and that the potency of inhibition depended upon the substitution patterns of the flavonoid molecules.