Subba Arunika, Rai Rohit, Prasad Ranjan Kumar, Shilall Isaac, Tamang Aditya Moktan
Department of Botany, Sikkim Alpine University, Main Campus, Kamrang, Namchi, 737126 Sikkim India.
Department of Zoology, Sikkim Alpine University, Main Campus, Kamrang, Namchi, 737126 Sikkim India.
In Silico Pharmacol. 2025 Apr 16;13(2):60. doi: 10.1007/s40203-025-00348-y. eCollection 2025.
The current study investigates the network pharmacology, molecular docking, and molecular dynamics (MD) simulation of Wall. (Oleaceae) to validate its ethnomedicinal applications in Type 2 Diabetes Mellitus (T2DM). Five major bioactive compounds were identified using IMPPAT and TCMSP databases, based on pharmacokinetic properties (OB > 20%, DL > 0.18). Target genes for these compounds were predicted using Swiss Target Prediction, focusing on human targets with a high confidence score. A protein-protein interaction (PPI) network was constructed using the STRING database, revealing significant interactions among 143 nodes and 1300 edges. Molecular docking analysis revealed strong binding affinities of quercetin (- 10.4 kcal/mol), tamarixetin (- 10.4 kcal/mol), and isorhamnetin (- 9.5 kcal/mol) with MMP9, forming hydrogen bonds with key residues such as ALA189, GLN227, and TYR248. Molecular dynamics (MD) simulations confirmed the stability of the quercetin-MMP9 and tamarixetin-MMP9 complexes, with low RMSD values (~ 0.151 nm). Further, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations revealed favorable binding free energies, with quercetin exhibiting the highest binding affinity (- 6.82 kJ/mol), followed by tamarixetin (4.60 kJ/mol) and isorhamnetin (10.16 kJ/mol), reinforcing their potential role as MMP9 inhibitors. The findings highlight the potential of bioactive compounds in managing T2DM, bridging traditional medicinal knowledge with modern computational tools to accelerate drug discovery and development. This integrative approach underscores the multifaceted pharmacological properties of , including antioxidant, anti-inflammatory, and potentially anti-obesity effects, aligning with broader health benefits beyond diabetes management. Further research and clinical validation are warranted to harness these natural compounds effectively for therapeutic development against T2DM and related metabolic disorders.
The online version contains supplementary material available at 10.1007/s40203-025-00348-y.
本研究调查了 [植物名称]（木犀科）的网络药理学、分子对接和分子动力学（MD）模拟，以验证其在 2 型糖尿病（T2DM）中的民族药用应用。基于药代动力学特性（OB＞20%，DL＞0.18），使用 IMPPAT 和 TCMSP 数据库鉴定了五种主要生物活性化合物。使用 Swiss Target Prediction 预测这些化合物的靶基因，重点关注具有高置信度分数的人类靶标。使用 STRING 数据库构建了蛋白质-蛋白质相互作用（PPI）网络，揭示了 143 个节点和 1300 条边之间的显著相互作用。分子对接分析显示槲皮素（-10.4 kcal/mol）、山柰酚（-10.4 kcal/mol）和异鼠李素（-9.5 kcal/mol）与基质金属蛋白酶 9（MMP9）具有很强的结合亲和力，与关键残基如 ALA189、GLN227 和 TYR248 形成氢键。分子动力学（MD）模拟证实了槲皮素-MMP9 和山柰酚-MMP9 复合物的稳定性，均方根偏差（RMSD）值较低（约 0.151 nm）。此外，分子力学泊松-玻尔兹曼表面积（MM-PBSA）计算显示出有利的结合自由能，槲皮素表现出最高的结合亲和力（-6.82 kJ/mol），其次是山柰酚（-4.60 kJ/mol）和异鼠李素（-10.16 kJ/mol），加强了它们作为 MMP9 抑制剂的潜在作用。这些发现突出了生物活性化合物在管理 T2DM 方面的潜力，将传统医学知识与现代计算工具相结合，以加速药物发现和开发。这种综合方法强调了 [植物名称] 的多方面药理特性，包括抗氧化、抗炎和潜在的抗肥胖作用，与糖尿病管理之外更广泛的健康益处相一致。有必要进行进一步的研究和临床验证，以有效地利用这些天然化合物开发针对 T2DM 和相关代谢紊乱的治疗方法。
在线版本包含可在 10.1007/s40203-025-00348-y 获得的补充材料。
