Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Int J Mol Sci. 2023 Jun 15;24(12):10195. doi: 10.3390/ijms241210195.
Diabetes is a chronic fast-growing metabolic disorder that is characterized by high blood glucose levels. L. has been used as a traditional remedy for various illnesses for many years, and, furthermore, its oil is used in the perfume and flavor industries. contains various metabolites, such as flavonoids, thiophenes, terpenes, sterols, and phenolics, with varied bioactivities. Flavonoids can inhibit carbohydrate-digesting enzymes, such as alpha-amylase, which is a convenient dietary strategy for controlling hyperglycemia. In the current investigation, the isolated flavonoids quercetagetin-6-O-(6-O-caffeoyl-β-D-glucopyranoside), quercetagetin-7-O-β-D-glucopyranoside, quercetagetin-6-O-β-D-glucopyranoside, minutaside A, patuletin-7-O-β-D-glucopyranoside, quercetagetin-7-methoxy-6-O-β-D-glucopyranoside, tagenols A and B, quercetagetin-3,7-dimethoxy-6-O-β-D-glucopyranoside, patuletin, quercetin-3,6-dimethyl ether, and quercetin-3-methyl ether from were assessed for their alpha-amylase inhibition (AAI) efficacy using an in vitro assay, as well as molecular docking, dynamics simulation, and ADMET analyses. Our findings show that quercetagetin-6-O-(6-O-caffeoyl-β-D-glucopyranoside) (), quercetagetin-7-O-β-D-glucopyranoside (), quercetagetin-6-O-β-D-glucopyranoside (), minutaside A (), patuletin-7-O-β-D-glucopyranoside (), and quercetagetin-7-methoxy-6-O-β-D-glucopyranoside () had a notable AAI capacity (ICs ranged from 7.8 to 10.1 μM) compared to acarbose (IC 7.1 μM). Furthermore, these compounds with the highest binding affinity among the tested flavonoids revealed high docking scores for AA (ranging from -12.171 to 13.882 kcal/mol) compared to that of acarbose (-14.668 kcal/mol). In MDS, these compounds were observed to show maximum stability and the greatest binding free energy, suggesting that they may contend with native ligands. In addition, the ADMET analysis showed that these active compounds had a broad span of drug-like, pharmacokinetic, and physicochemical features and did not possess any considerable undesired effects. The current results suggest the potential of these metabolites as AAI candidates. However, further in vivo and mechanistic studies are warranted to specify the efficacy of these metabolites.
糖尿病是一种慢性、快速发展的代谢紊乱，其特征是血糖水平升高。黄连多年来一直被用作治疗各种疾病的传统药物，此外，其油还用于香水和香料行业。黄连含有多种代谢物，如类黄酮、噻吩、萜类、甾醇和酚类，具有多种生物活性。类黄酮可以抑制碳水化合物消化酶，如α-淀粉酶，这是控制高血糖的一种方便的饮食策略。在当前的研究中，从黄连中分离得到的黄酮类化合物槲皮苷-6-O-(6-O-咖啡酰基-β-D-吡喃葡萄糖苷)、槲皮苷-7-O-β-D-吡喃葡萄糖苷、槲皮苷-6-O-β-D-吡喃葡萄糖苷、小檗胺 A、白杨素-7-O-β-D-吡喃葡萄糖苷、槲皮苷-7-甲氧基-6-O-β-D-吡喃葡萄糖苷、塔格醇 A 和 B、槲皮苷-3,7-二甲氧基-6-O-β-D-吡喃葡萄糖苷、白杨素、槲皮素-3,6-二甲醚和槲皮素-3-甲基醚被评估了它们的α-淀粉酶抑制（AAI）功效使用体外测定法，以及分子对接、动力学模拟和 ADMET 分析。我们的研究结果表明，槲皮苷-6-O-(6-O-咖啡酰基-β-D-吡喃葡萄糖苷)（）、槲皮苷-7-O-β-D-吡喃葡萄糖苷（）、槲皮苷-6-O-β-D-吡喃葡萄糖苷（）、小檗胺 A（）、白杨素-7-O-β-D-吡喃葡萄糖苷（）和槲皮苷-7-甲氧基-6-O-β-D-吡喃葡萄糖苷（）与阿卡波糖（IC 7.1 μM）相比，具有显著的 AAI 能力（IC 范围为 7.8 至 10.1 μM）。此外，与阿卡波糖（-14.668 kcal/mol）相比，在所测试的黄酮类化合物中具有最高结合亲和力的这些化合物对 AA 具有高对接评分（范围为-12.171 至 13.882 kcal/mol）。在 MDS 中，这些化合物被观察到表现出最大的稳定性和最大的结合自由能，表明它们可能与天然配体竞争。此外，ADMET 分析表明，这些活性化合物具有广泛的药物样、药代动力学和物理化学特征，并且没有任何明显的不良影响。目前的结果表明，这些代谢物可能是 AAI 的候选物。然而，需要进一步的体内和机制研究来确定这些代谢物的疗效。
