Agriculture Plant Biotechnology Laboratory (ARL-316), University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, Delhi, 110078, India.
Sci Rep. 2024 Oct 22;14(1):24936. doi: 10.1038/s41598-024-75570-3.
Diabetes is a metabolic condition defined by abnormal blood sugar levels. Targeting starch-hydrolyzing enzymes and Dipeptidyl Peptidase 4 (DPP-4) expressed on the surface of numerous cells is one of the key strategies to lower the risk of Type-2 diabetes mellitus (T2DM). Dalbergia sissoo Roxb. bark (DSB) extracts have been reported to have anti-diabetic properties. This study intended to scientifically validate use of alcoholic and hydro-alcoholic extracts of DSB for T2DM by conducting preliminary phytochemical investigations, characterising potential phytochemicals using Fourier transform infrared (FT-IR) spectroscopy and Gas chromatography-mass spectrometry (GC-MS) analysis followed by comprehensive in-silico analysis. A qualitative phytochemical evaluation indicated the presence of alkaloids, phenolics, glycosides, conjugated acids and flavonoids. Ethanolic extracts showed highest total phenolic content (TPC) (127.072 ± 14.08031 μg GAE/g dry extract) and total flavonoid content (106.911 ± 5.84516 μg QE /g dry extract). Further FT-IR spectroscopy also revealed typical band values associated with phenol, alcohol, alkene, alkane and conjugated acid functional groups. The GC-MS analysis identified 139 compounds, 18 of which had anti-diabetic potential. In-silico ADMET analysis of potential compounds revealed 15 compounds that followed Lipinski's rule and demonstrated drug-like properties, as well as good oral bioavailability. Molecular docking was utilised to analyse their potential to interact with three targets: α-amylase, α-glucosidase, and DPP-4, which are crucial in managing diabetes-related problems. Molecular Docking analysis and membrane permeability test utilising the PerMM platform revealed that compounds in the extracts, such as Soyasapogenol B and Corydine, had better interactions and permeability across the plasma membrane than standard drugs in use. Molecular dynamics simulations also showed that selected compounds remained stable upon interaction with α-amylase. Overall, using the in-silico approaches it was predicted that DSB extracts contain potential phytochemicals with diverse anti-diabetic properties. It further needs to be investigated for possible development as formulation or drug of choice for treating T2DM.
糖尿病是一种以血糖水平异常为特征的代谢性疾病。靶向多种细胞表面表达的淀粉水解酶和二肽基肽酶 4（DPP-4）是降低 2 型糖尿病（T2DM）风险的关键策略之一。Dalbergia sissoo Roxb.树皮（DSB）提取物已被报道具有抗糖尿病作用。本研究旨在通过进行初步的植物化学研究、使用傅里叶变换红外（FT-IR）光谱和气相色谱-质谱（GC-MS）分析对潜在的植物化学物质进行表征，以及进行全面的计算机模拟分析，从科学上验证 DSB 的醇提物和水醇提物在 T2DM 中的应用。定性植物化学评价表明存在生物碱、酚类、糖苷、共轭酸和类黄酮。醇提物显示出最高的总酚含量（TPC）（127.072 ± 14.08031 μg GAE/g 干提取物）和总黄酮含量（106.911 ± 5.84516 μg QE/g 干提取物）。进一步的 FT-IR 光谱还显示了与酚类、醇类、烯烃、烷烃和共轭酸官能团相关的典型谱带值。GC-MS 分析鉴定了 139 种化合物，其中 18 种具有抗糖尿病潜力。潜在化合物的计算机模拟 ADMET 分析表明，有 15 种化合物符合利宾斯基规则，具有类药性，并且具有良好的口服生物利用度。分子对接用于分析它们与三个靶标的潜在相互作用：α-淀粉酶、α-葡萄糖苷酶和 DPP-4，这三个靶标在管理糖尿病相关问题中非常重要。分子对接分析和使用 PerMM 平台进行的膜通透性测试表明，提取物中的化合物，如 Soyasapogenol B 和 Corydine，与现有的标准药物相比，在穿过质膜时具有更好的相互作用和通透性。分子动力学模拟还表明，所选化合物在与α-淀粉酶相互作用时保持稳定。总的来说，使用计算机模拟方法预测 DSB 提取物含有具有多种抗糖尿病特性的潜在植物化学物质。还需要进一步研究其作为治疗 T2DM 的配方或首选药物的可能性。
