Abstract：
As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT1R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT1R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT1R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT1R. The association constants were (2.40 ± 0.02) × 104 M-1 for naringenin (5.22 ± 0.26) × 104 M-1 for pinocembrin, and (4.27 ± 0.14) × 104 M-1 for chrysin, respectively. These compounds can bind with AT1R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT1R column for screening and analyzing bioactive compounds in Tibetan medicines.
摘要：
由于缺乏现代技术，藏药的研究在确定生物活性化合物方面受到了阻碍。在这里，我们使用固定的血管紧张素II1型受体（AT1R）通过由卤代烷烃脱卤酶触发的一步法建立了色谱方法。使用固定化AT1R和MS筛选并鉴定了来自Choerospondiasaxillaris（广藻）的生物活性化合物。使用正面分析（FA）和吸附能分布（AED）来评估缔合常数。分子对接用于研究结合构型，和表面效率指数，结合效率指数，计算配体亲脂性效率（LLE）以评估药物样特性。结果确定了柚皮素，pinocembrin,和chrysin作为与广枣AT1R特异性结合的化合物。FA和AED证实在这些化合物和AT1R之间仅存在一种类型的结合位点。柚皮素的缔合常数为（2.40±0.02）×104M-1（5.22±0.26）×104M-1，chrysin为(4.27±0.14)×104M-1，分别。这些化合物可以通过正构结合口袋与AT1R结合。柚皮素表现出比pinocembrin和chrysin更好的LLE。这些结果证实了使用固定化AT1R柱筛选和分析藏药中生物活性化合物的可行性。
