Moussa Ashaimaa Y, Alanzi Abdullah, Luo Jinhai, Chung Sookja Kim, Xu Baojun
Department of Pharmacognosy, Faculty of Pharmacy Ain Shams University Cairo Egypt.
Department of Pharmacognosy, College of Pharmacy King Saud University Riyadh Saudi Arabia.
Food Sci Nutr. 2024 Feb 22;12(5):3612-3627. doi: 10.1002/fsn3.4032. eCollection 2024 May.
In contrast to its widespread traditional and popular culinary use to reduce weight, (adzuki beans) was not subjected to sufficient scientific scrutiny. Particularly, its saponins whose role was never investigated before to unveil the beans' antidiabetic and anti-obesity effects. Four vital pancreatic and intestinal carbohydrate enzymes were selected to assess the potency of the triterpenoidal saponins of to bind and activate these proteins through high-precision molecular modeling and dynamics mechanisms with accurate molecular mechanics Generalized Born Surface Area (MMGBSA) energy calculations; thus, recognizing their anti-obesity potential. Our results showed that adzukisaponin VI and adzukisaponin IV were the best compounds in the -amylase and -glucosidase enzymatic grooves, respectively. Adzukisaponin VI and angulasaponin C were the best fitting in the N-termini of sucrase-isomaltose (SI) enzyme, and angulasaponin C was the best scoring compound in maltase-glucoamylase C-termini. All of them outperformed the standard drug acarbose. These compounds in their protein complexes were selected to undergo molecular simulations of the drug-bound protein compared to the apo-protein through 100 ns, which confirmed the consistency of binding to the key amino acid residues in the four enzyme pockets with the least propensity of unfolding. Detailed analysis is given of the different polar and hydrophobic binding interactions of docked compounds. While maltase-adzukisaponin VI complex scored the lowest MMGBSA free energy of -67.77 Kcal/mol, α-amylase complex with angulasaponin B revealed the free binding energy of -74.18 Kcal/mol with a dominance of van der Waals energy (ΔEVDW) and the least change from the start to the end of the simulation time. This study will direct researchers to the significance of isolating the pure adzuki saponin components to conduct future in vitro and in vivo experimental works and even clinical trials.
与广泛的传统和流行烹饪用途（用于减肥）相反，（赤小豆）并未受到充分的科学审查。特别是其皂苷，其作用以前从未被研究过，以揭示该豆类的抗糖尿病和抗肥胖作用。选择了四种重要的胰腺和肠道碳水化合物酶，通过高精度分子建模和动力学机制以及精确的分子力学广义玻恩表面积（MMGBSA）能量计算，来评估赤小豆三萜皂苷结合和激活这些蛋白质的能力；从而认识到它们的抗肥胖潜力。我们的结果表明，赤小豆皂苷VI和赤小豆皂苷IV分别是在α-淀粉酶和α-葡萄糖苷酶酶槽中表现最佳的化合物。赤小豆皂苷VI和角鲨皂苷C在蔗糖酶-异麦芽糖酶（SI）酶的N端最匹配，而角鲨皂苷C在麦芽糖酶-葡糖淀粉酶C端得分最高。它们都优于标准药物阿卡波糖。与无配体蛋白相比，这些化合物在其蛋白质复合物中经过100纳秒的药物结合蛋白分子模拟，证实了它们与四个酶口袋中的关键氨基酸残基结合的一致性，且展开倾向最小。对对接化合物的不同极性和疏水结合相互作用进行了详细分析。虽然麦芽糖酶-赤小豆皂苷VI复合物的MMGBSA自由能最低，为-67.77千卡/摩尔，但α-淀粉酶与角鲨皂苷B的复合物显示自由结合能为-74.18千卡/摩尔，范德华能（ΔEVDW）占主导，且从模拟开始到结束的变化最小。这项研究将引导研究人员认识到分离纯赤小豆皂苷成分对于开展未来的体外和体内实验工作乃至临床试验的重要性。
