The increasing incidence of neurodegenerative diseases (NDDs) has stressed the need to develop new treatments. In this regard, alkaloids from medicinal plants are being identified and developed as inhibitors of acetylcholinesterase, other enzymes, and receptors associated with the onset of NDDs. Nardostachys jatamansi, a medicinal herb native to the Himalayan region and belonging to the Caprifoliaceae family, has long been used in Indian traditional medicine to treat neurobiological symptoms. In this study, we have isolated and identified the major alkaloids from N. jatamansi using LC–MS/MS analysis. The dried root extract of N. jatamansi contained actinidine and glaziovine as its major alkaloids. These compounds were identified using LC–MS/MS fragmentation pattern and purified by semi-preparative HPLC. The molecular docking analysis was performed for the purified alkaloids with 15 target proteins associated with NDDs pathology. Notably, actinidine and glaziovine showed better interaction energy with the acetylcholine esterase, VGF nerve growth factor, cyclin-dependent kinase, and glycogen synthase kinase when compared to the clinically used drugs memantine and tacrine. Glaziovine also showed better interaction energy when docking was performed with GluN1/GluN2B NMDA receptor, β-secretase, tyrosine phosphorylation regulation kinase, necrosis factor-kappa, adenosine A2A receptor, alpha-synuclein, beta-site amyloid precursor protein cleaving enzyme 1, c-Jun N terminal kinase, monoamine oxidase B, compared to tacrine, galantamine, and memantine. Furthermore, actinidine and glaziovine showed borderline cytotoxicity on PC12 and SH-SY 5Y cells with IC₅₀ values ranging from 85.32 ± 0.87 μM, and 92.12 ± 0.56 μM, respectively, indicating that these alkaloids can be further developed as promising drug leads.

神经退行性疾病 (NDD) 发病率的增加强调了开发新疗法的必要性。在这方面，药用植物中的生物碱正在被鉴定和开发为乙酰胆碱酯酶、其他酶和与 NDD 发作相关的受体的抑制剂。Nardostachys jatamansi是一种原产于喜马拉雅地区的药草，属于 Caprifoliaceae 家族，长期以来一直在印度传统医学中用于治疗神经生物学症状。在这项研究中，我们使用 LC-MS/MS 分析从N. jatamansi中分离和鉴定了主要生物碱。N. jatamansi的干燥根提取物含有actinidine和glaziovine作为其主要生物碱。这些化合物使用 LC-MS/MS 碎裂模式进行鉴定，并通过半制备型 HPLC 进行纯化。对纯化的生物碱与15个与NDDs病理学相关的靶蛋白进行分子对接分析。值得注意的是，与临床使用的药物美金刚和他克林相比，actinidine 和 glaziovine 与乙酰胆碱酯酶、VGF 神经生长因子、细胞周期蛋白依赖性激酶和糖原合酶激酶的相互作用能更好。当与 GluN1/GluN2B NMDA 受体、β-分泌酶、酪氨酸磷酸化调节激酶、坏死因子-κ、腺苷 A2A 受体、α-突触核蛋白、β-位点淀粉样前体蛋白裂解酶 1、c 进行对接时，Glaziovine 还显示出更好的相互作用能-Jun N末端激酶，与他克林、加兰他敏和美金刚相比，单胺氧化酶 B。此外，actinidine 和 glaziovine 对具有 IC 的 PC12 和 SH-SY 5Y 细胞显示出临界细胞毒性_{50 个}值分别在 85.32 ± 0.87 μM 和 92.12 ± 0.56 μM 范围内，表明这些生物碱可以进一步开发为有前景的药物先导物。