Department of Botany, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman.
Molecules. 2022 Feb 16;27(4):1322. doi: 10.3390/molecules27041322.
The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the α-glucosidase inhibitory assay. However, the EtOAc fraction with IC = 0.14 ± 0.06 µg/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC = 1.47 ± 0.14 and 2.18 ± 0.30 µg/mL, respectively. Moreover, the acarbose showed an IC = 377.26 ± 1.20 µg/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC = 23.97 ± 0.14 µg/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified-three and two in NIM and PIM, respectively-as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of α-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds-dihydrocatalpol and leucosceptoside A-from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus.
最近的研究调查了 的粗提物（甲醇）和乙酸乙酯（EtOAc）；氯仿；正丁醇；正己烷；水相部分的体外抗糖尿病作用，并首次通过 ESI-LC-MS 分析对活性 EtOAc 部分进行了化学成分的鉴定，通过正离子化模式（PIM）和负离子化模式（NIM）；通过标准方法通过计算分析进一步验证了鉴定的化合物。粗提物和各馏分对α-葡萄糖苷酶抑制试验表现出明显的活性。然而，EtOAc 馏分的 IC = 0.14 ± 0.06 µg/mL 在所用馏分中表现出最大的潜力，其次是 MeOH 和 n-hexane 提取物，IC = 1.47 ± 0.14 和 2.18 ± 0.30 µg/mL。此外，阿卡波糖的 IC = 377.26 ± 1.20 µg/mL，而氯仿馏分的抑制作用最小，IC = 23.97 ± 0.14 µg/mL。由于 EtOAc 馏分的重要性，当对其化学成分进行分析时，它呈现出 16 种化合物，其中黄酮类化合物占主导地位，并提供了 8 种化合物，其中 6 种在 NIM 中鉴定，2 种在 PIM 中鉴定。此外，还鉴定了五种三萜类化合物-三种和两种在 NIM 和 PIM 中，以及两种生物碱，均在 PIM 中检测到。EtOAc 馏分还含有一种在 PIM 中发现的酚类化合物。已检测到的黄酮类、三萜类、生物碱和酚类化合物以其多种生物医学应用而闻名。具有强大活性的 EtOAc 馏分经过计算分析，进一步验证了α-葡萄糖苷酶的重要性，以确定负责化合物。基于 100 ns 的分子动力学模拟轨迹的药代动力学估算和蛋白质-配体分子对接结果表明，两种生物活性化合物-二氢梓醇和莱苏斯考甙 A-来自 EtOAc 馏分，表现出良好的类药性和稳定的构象；因此，这些生物活性化合物可能是基于与重要残基的分子间相互作用、对接评分和结合自由能估计的α-葡萄糖苷酶抑制剂的潜在候选药物。所述研究结果表明， 是生物活性化合物的丰富来源，为治疗糖尿病提供了潜在的方法；特别是二氢梓醇和莱苏斯考甙 A 可能是治疗糖尿病的新型药物开发的极好的治疗选择。
