目的 研究葒草素和異葒草素降血糖的靶點(diǎn)及其體外活性。方法 從蛋白質(zhì)數(shù)據(jù)庫(kù)（www.rcsb.org）獲取糖尿病相關(guān)靶點(diǎn)蛋白結(jié)構(gòu)，利用虛擬分子對(duì)接打分評(píng)價(jià)葒草素和異葒草素與糖尿病相關(guān)靶點(diǎn)的結(jié)合強(qiáng)弱；基于分子對(duì)接的結(jié)果，采用熒光標(biāo)記的1-脫氧葡萄糖（1-NBDG）、4-硝基苯基-α-D-葡萄糖苷PNDG（PNPG）、對(duì)硝基苯酚磷酸酯（pNPP）作為底物對(duì)葒草素和異葒草素進(jìn)行體外抑制α-葡萄糖糖苷酶、鈉–葡萄糖協(xié)同轉(zhuǎn)運(yùn)蛋白2（SGLT2）和蛋白酪氨酸磷酸酶1B（PTP1B）活性評(píng)價(jià)。結(jié)果 葒草素與α-葡萄糖苷酶、SGLT2、和PTP1B的分子對(duì)接得分分別為-5.67、-9.32、-4.75，異葒草素與α-葡萄糖苷酶、SGLT2和PTP1B的分子對(duì)接得分分別為-5.34、-8.63、-4.93，而陽(yáng)性對(duì)照藥與靶標(biāo)的分子對(duì)接打分依次是-5.58、-9.79、-9.28。體外實(shí)驗(yàn)顯示，葒草素對(duì)α-葡萄糖苷酶、SGLT2、PTP1B的抑制率依次是（16.7±5.8）%、（15.4±1.2）%、（3.0±0.5）%，異葒草素對(duì)α-葡萄糖苷酶、SGLT2、PTP1B的抑制率依次是（11.8±3.8）%、（9.4±1.1）%、（-3.8±0.6）%，而陽(yáng)性對(duì)照對(duì)α-葡萄糖苷酶、SGLT2、PTP1B的抑制率依次為（63.7±5.8）%、（92.7±8.8）%、（73.4±8.3）%。結(jié)論 葒草素和異葒草素對(duì)SGLT2和α-葡萄糖苷酶具有一定的抑制活性，對(duì)PTP1B幾乎沒有抑制作用，且葒草素的體外活性略強(qiáng)于異葒草素，葒草素有可能作為一類具有雙靶點(diǎn)作用的降血糖藥物的先導(dǎo)化合物。

Objective To study the hypoglycemic target of orientin and isoorientin and their activities in vitro. Methods The structure of diabetes-related target proteins was obtained from the www.rcsb.org database, and the binding of orientin and isorientin to diabetes-related target proteins was evaluated by virtual molecular docking score, the inhibitory effects of orientin and isoorientin on α-glucosidase, SGLT2, and PTP1B in vitro were evaluated by using 1-NBDG, PNDG and PNPP as substrates. Results The molecular docking scores of orientin with α-glucosidase, SGLT2, and PTP1B were −5.67, −9.32, and −4.75, respectively. Molecular docking scores of isoorientin with α-glucosidase, SGLT2, and PTP1B were −5.34, −8.63, and −4.93, respectively, while the molecular docking scores of positive control drug and target were −5.58, −9.79 and −9.28, respectively. The inhibition rates of orientin on α-glucosidase, SGLT2, and PTP1B were (16.7 ± 5.8) %, (15.4 ± 1.2) %, and (3.0 ± 0.5) %, respectively. The inhibitory rates of isoorientin on α-glucosidase, SGLT2, and PTP1B were (11.8 ± 3.8) %, (9.4 ± 1.1) %, and (−3.8± 0.6) %, respectively. The inhibition rates of α-glucosidase, SGLT2, and PTP1B in positive control were (63.7± 5.8) %, (92.7 ± 8.8) % ,and (73.4 ± 8.3) %, respectively.Conclusion Orientin and isorientin showed certain inhibitory activities on SGLT2 and α-glucosidase, and had little inhibitory effect on PTP1B, and oriorientin was slightly stronger than isorientin in vitro, orientin may be a potential lead compound for a class of hypoglycemic agents with dual-target effects.

R285

陜西省自然科學(xué)基礎(chǔ)研究計(jì)劃（2019JQ-401）；陜西中醫(yī)藥大學(xué)校級(jí)科研課題（2020GP32）