Biswas Suvro, Mita Mohasana Akter, Islam Shirmin, Biswas Shovon, Akhtar-E-Ekram Md, Zaman Shahriar, Uddin Md Salah, Saleh Md Abu
Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Department of Industrial and Production Engineering, Bangladesh University of Engineering and Technology, Dhaka, 1000, Bangladesh.
Comput Biol Med. 2025 Mar;186:109680. doi: 10.1016/j.compbiomed.2025.109680. Epub 2025 Jan 21.
Diabetes mellitus (DM) can be treated with various medications. However, individuals in underdeveloped countries may face challenges in using these treatments due to side effects and high costs. Anti-diabetic medications can inhibit enzymes, such as α-amylase, which is responsible for breaking down carbohydrates. In this investigation, 16 phytoconstituents were identified from Pterocarpus santalinus leaf extract through GC-MS analysis, and their significant antioxidant activities were noted. Among these, the pure compound lupeol demonstrated α-amylase inhibition activity of 86.13 ± 1.27 % (IC = 58.50 ± 0.83 μg/mL) in vitro. Additionally, lupeol showed the highest binding affinity in silico using PyRx and CB-Dock, with values of -9.5 and -9.3 kcal/mol, respectively. The in silico analysis also indicated that lupeol possesses acceptable ADMET properties, suggesting its potential as an anti-diabetic drug. A molecular dynamics simulation lasting 500 ns was conducted to evaluate hydrogen bonds, RMSF, RMSD, Rg, and SASA, confirming the stability and integrity of the docking scenarios. In STZ-induced diabetic mice, lupeol significantly reduced blood glucose levels by 70.82 % from day 0 to day 28. Furthermore, lupeol markedly decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while improving high-density lipoprotein cholesterol (HDL-C) levels in these mice. The antidiabetic effect of lupeol was further validated through histological examinations of the pancreas, heart, kidney, and liver of treated mice, alongside correlation analysis, CAP, and ANOSIM tests. Based on the findings from the in vitro, in silico, and in vivo investigations, this study concludes that lupeol may have potential anti-diabetic effects through the inhibition of the α-amylase enzyme.
糖尿病（DM）可用多种药物治疗。然而，由于副作用和高成本，欠发达国家的个人在使用这些治疗方法时可能面临挑战。抗糖尿病药物可以抑制酶，如负责分解碳水化合物的α-淀粉酶。在本研究中，通过气相色谱-质谱联用（GC-MS）分析从降香檀叶提取物中鉴定出16种植物成分，并注意到它们具有显著的抗氧化活性。其中，纯化合物羽扇豆醇在体外表现出86.13±1.27%的α-淀粉酶抑制活性（IC=58.50±0.83μg/mL）。此外，使用PyRx和CB-Dock进行的计算机模拟分析表明，羽扇豆醇具有最高的结合亲和力，分别为-9.5和-9.3 kcal/mol。计算机模拟分析还表明，羽扇豆醇具有可接受的药物代谢动力学（ADMET）性质，表明其具有作为抗糖尿病药物的潜力。进行了持续500纳秒的分子动力学模拟，以评估氢键、均方根波动（RMSF）、均方根偏差（RMSD）、回旋半径（Rg）和溶剂可及表面积（SASA），证实了对接方案的稳定性和完整性。在链脲佐菌素（STZ）诱导的糖尿病小鼠中，从第0天到第28天，羽扇豆醇显著降低血糖水平达70.82%。此外，羽扇豆醇显著降低了这些小鼠的总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-C）水平，同时提高了高密度脂蛋白胆固醇（HDL-C）水平。通过对治疗小鼠的胰腺、心脏、肾脏和肝脏进行组织学检查，以及相关性分析、聚类分析（CAP）和相似性分析（ANOSIM）测试，进一步验证了羽扇豆醇的抗糖尿病作用。基于体外、计算机模拟和体内研究结果，本研究得出结论，羽扇豆醇可能通过抑制α-淀粉酶而具有潜在的抗糖尿病作用。
