Katipearachchi Sugandhi, Faizan Mishal, Kalansuriya Pabasara, Attanayake Anoja Priyadarshani, De Silva Nayomi Deshani
Faculty of Applied Sciences, Lincoln University College, Kota Bharu, Malaysia.
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka.
Chem Biodivers. 2025 Aug 22:e01525. doi: 10.1002/cbdv.202501525.
Gymnema sylvestre R. Br. (gurmar, Asclepiadaceae) and Trigonella foenum-graecum L. (Fenugreek, Fabaceae) are medicinal plants with proven antidiabetic activity. This study employed the construction of a 221-compound library from G. sylvestre and T. foenum-graecum for virtual screening against α-amylase and α-glucosidase target proteins. It aimed to analyze phytochemical-target protein interactions via molecular dynamic simulations and validation of findings using in vitro antidiabetic assays. Bioinformatics tools facilitated virtual screening, molecular dynamics simulations, and ADMETox analysis. The α-amylase and α-glucosidase inhibitory potentials were screened in vitro using 50% EtOH extracts of G. sylvestre leaves and T. foenum-graecum seeds with acarbose as the reference compound. Trigoneoside XIIa (-9.1 kcal/mol) and trigofoenoside G (-9.8 kcal/mol) derived from T. foenum-graecum and gymnemasaponin V (-9.7 kcal/mol) derived from G. sylvestre showed the most stable binding interaction with the target proteins. In vitro assays further revealed that T. foenum-graecum seed extract showed the highest α-amylase inhibition (IC = 12.09 ± 2.13 mg/mL) and α-glucosidase inhibition (IC = 5.23 ± 0.33 mg/mL). Trigoneoside XIIa, trigofoenoside G, and gymnemasaponin V were identified as promising drug candidates for the development of antidiabetic drug leads, further validating the in vitro α-amylase and α-glucosidase inhibitory potentials.
匙羹藤（Gymnema sylvestre R. Br.，萝摩科）和胡芦巴（Trigonella foenum - graecum L.，豆科）是具有已证实抗糖尿病活性的药用植物。本研究构建了一个包含221种化合物的文库，该文库来自匙羹藤和胡芦巴，用于针对α - 淀粉酶和α - 葡萄糖苷酶靶蛋白进行虚拟筛选。其目的是通过分子动力学模拟分析植物化学物质与靶蛋白的相互作用，并使用体外抗糖尿病试验验证研究结果。生物信息学工具促进了虚拟筛选、分子动力学模拟和ADMETox分析。使用匙羹藤叶和胡芦巴种子的50%乙醇提取物，以阿卡波糖作为参考化合物，在体外筛选α - 淀粉酶和α - 葡萄糖苷酶抑制潜力。源自胡芦巴的胡芦巴苷XIIa（-9.1千卡/摩尔）和胡芦巴新苷G（-9.8千卡/摩尔）以及源自匙羹藤的匙羹藤皂苷V（-9.7千卡/摩尔）与靶蛋白表现出最稳定的结合相互作用。体外试验进一步表明，胡芦巴种子提取物显示出最高的α - 淀粉酶抑制率（IC = 12.09 ± 2.13毫克/毫升）和α - 葡萄糖苷酶抑制率（IC = 5.23 ± 0.33毫克/毫升）。胡芦巴苷XIIa、胡芦巴新苷G和匙羹藤皂苷V被确定为开发抗糖尿病药物先导物的有前景的候选药物，进一步验证了体外α - 淀粉酶和α - 葡萄糖苷酶的抑制潜力。
