ALNadhari Saleh, Alsakkaf Waleed A A, Albarakat Faisal Abdulaziz
Deanship of Scientific Research, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Botany & Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Biotechnol Appl Biochem. 2025 Aug;72(4):936-953. doi: 10.1002/bab.2709. Epub 2024 Dec 23.
Targeting alpha-glucosidase (maltase-glucoamylase [MGAM] and sucrase-isomaltase [SI]) under diabetes conditions is important to overcome hyperglycemia. Moreover, it is necessary to mitigate hyperglycemia-mediated oxidative stress to evade the progression of diabetes-associated secondary complications. Hence, in the present study, under-explored Nyctanthes arbor-tristis flowers (NAFs) were studied for inhibition of alpha-glucosidase activities. The NAF methanolic extract (NAFME) was prepared. Through liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) analysis, various phytocompounds belonging to different classes-flavonoids, iridoid glycosides, proanthocyanidin, anthocyanin, polyphenol, phenolic acid, fatty acid ester, and carotenoid-were identified. NAFME showed in vitro antioxidant activity. NAFME inhibited maltase, sucrase, glucoamylase, and isomaltase in mixed mode with Ki values of 179.93, 176.38, 126.03, and 201.56 µg/mL, respectively. In silico screening of phytocompounds identified in NAFME indicated that hinokiflavone (HKF), pelargonidin-3-O-glucoside (PG), isorhamnetin-3-glucoside-7-rhamnoside (IGR), and petunidin-3-rutinoside (PR) showed better interactions with different subunits of human alpha-glucosidase, namely, N-terminal (Nt-MGAM and Nt-SI) and C-terminal (Ct-MGAM and Ct-SI). Molecular dynamics (MD) simulation, binding free energy study (molecular mechanics-generalized Born surface area [MM/GBSA]), and post-MD simulation studies (principal component analysis [PCA] and dynamic cross-correlation matrix [DCCM]) provided an in-depth understanding of these ligands' interactions with proteins. The overall efficacy of NAFME against oxidative stress and alpha-glucosidase in vitro is understood. Moreover, in silico analysis has shown the possible potential of HKF, PG, IGR, and PR to act as alpha-glucosidase inhibitors. Further studies on the antidiabetic potential of NAFME, HKF, PG, IGR, and PR in in vivo conditions are required to fully unveil the applicability of NAFME in the management of T2DM as a complementary medicine.
在糖尿病条件下靶向α-葡萄糖苷酶（麦芽糖酶-葡糖淀粉酶[MGAM]和蔗糖酶-异麦芽糖酶[SI]）对于克服高血糖症很重要。此外，减轻高血糖介导的氧化应激以避免糖尿病相关继发性并发症的进展也很有必要。因此，在本研究中，对研究较少的夜花（NAFs）进行了α-葡萄糖苷酶活性抑制研究。制备了NAF甲醇提取物（NAFME）。通过液相色谱/电喷雾电离串联质谱（LC-ESI/MS/MS）分析，鉴定出了属于不同类别的各种植物化合物——黄酮类、环烯醚萜苷、原花青素、花青素、多酚、酚酸、脂肪酸酯和类胡萝卜素。NAFME表现出体外抗氧化活性。NAFME以混合模式抑制麦芽糖酶、蔗糖酶、葡糖淀粉酶和异麦芽糖酶，其Ki值分别为179.93、176.38、126.03和201.56μg/mL。对NAFME中鉴定出的植物化合物进行的计算机模拟筛选表明，扁柏黄酮（HKF）、天竺葵素-3-O-葡萄糖苷（PG）、异鼠李素-3-葡萄糖苷-7-鼠李糖苷（IGR）和矮牵牛素-3-芸香糖苷（PR）与人α-葡萄糖苷酶的不同亚基，即N端（Nt-MGAM和Nt-SI）和C端（Ct-MGAM和Ct-SI）表现出更好的相互作用。分子动力学（MD）模拟、结合自由能研究（分子力学-广义玻恩表面积[MM/GBSA]）以及MD后模拟研究（主成分分析[PCA]和动态交叉相关矩阵[DCCM]）深入了解了这些配体与蛋白质的相互作用。了解了NAFME在体外对氧化应激和α-葡萄糖苷酶的总体功效。此外，计算机模拟分析表明，HKF、PG、IGR和PR有可能作为α-葡萄糖苷酶抑制剂。需要对NAFME、HKF、PG、IGR和PR在体内条件下的抗糖尿病潜力进行进一步研究，以充分揭示NAFME作为辅助药物在2型糖尿病管理中的适用性。
