Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
Sci Rep. 2023 Feb 10;13(1):2444. doi: 10.1038/s41598-023-29446-7.
Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated for their pharmacological potential. In the present study, the efforts have been made to isolate the compound(s) from Grewia tiliaefolia Vahl., plant known for its ameliorative effect on brain related diseases such as anxiety, depression, cognitive disorders and Parkinson's disease. Plant extract was subjected to isolation of compound(s) using column chromatography and isolated compound was characterized by NMR FTIR and LCMS. The isolated compound was novel with the IUPAC name of the compound is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated as A-1 and has not been reported before. A-1 was further evaluated for its antioxidant potential using in vitro antioxidant assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay and reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory potential of A-1 and extract was analysed. Results showed that A-1 exhibited significantly higher antioxidant activity in both DPPH and RPA assay as compared to plant extract. In case of AChE inhibitory activity again, A-1 has shown significantly higher activity as compared to plant extract. In silico study was conducted to predict its action on proteins playing crucial role in neurological and neurodegenerative disorders such as gamma amino butyric acid (GABA) receptor and glutamate α amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu AMPA) receptor in epilepsy and AChE enzyme in Alzheimer's diseases. The compound has shown interaction in following order: AChE > GABA receptor > Glu AMPA receptor. Further, molecular dynamic simulations and ADME studies of A-1 and AChE enzyme revealed that A-1 yielded good results in all parameters and hence can relieve Alzheimer's like symptoms.
药用植物具有多种生物活性的植物化学物质。目前，已经从药用植物中分离出这些化合物，并对其药理潜力进行了鉴定和评价。在本研究中，我们从 Grewia tiliaefolia Vahl. 中分离化合物，这种植物因对与大脑相关的疾病（如焦虑、抑郁、认知障碍和帕金森病）具有改善作用而闻名。采用柱层析法对植物提取物进行化合物分离，用 NMR FTIR 和 LCMS 对分离得到的化合物进行了表征。该化合物是一种新型化合物，其 IUPAC 名称为丙基 3-羟基-10,13-二甲基-6,7,8,9,10,11,12,13,14,15,16,17-十二氢-3H-环戊[a]菲-17-羧酸酯，命名为 A-1，以前没有报道过。进一步采用体外抗氧化测定（2,2-二苯基-1-苦基肼水合物（DPPH）测定法和还原力测定法（RPA））对 A-1 的抗氧化潜力进行了评价。还分析了 A-1 和提取物的乙酰胆碱酯酶（AChE）抑制潜力。结果表明，与植物提取物相比，A-1 在 DPPH 和 RPA 测定中均表现出更高的抗氧化活性。在 AChE 抑制活性方面，A-1 的活性也明显高于植物提取物。进行了计算机模拟研究，以预测其对在神经和神经退行性疾病中起关键作用的蛋白质的作用，如癫痫中的γ-氨基丁酸（GABA）受体和谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（Glu AMPA）受体，以及阿尔茨海默病中的 AChE 酶。该化合物的相互作用顺序为：AChE>GABA 受体>Glu AMPA 受体。此外，A-1 和 AChE 酶的分子动力学模拟和 ADME 研究表明，A-1 在所有参数中都取得了良好的效果，因此可以缓解类似阿尔茨海默病的症状。
