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Purification, identification and in silico models of alkaloids from Nardostachys jatamansi — bioactive compounds for neurodegenerative diseases

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Abstract

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.

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Acknowledgements

The authors gratefully acknowledge Dr. Mohinder Singh (Ministry of Ayush), District Nodal officer, State Medicinal Plant Board (SMDP) Himachal Pradesh, Shimla, India for providing the plant samples. We also thank the management of SRM Institute of Science and Technology, College of Engineering, and Department of Biotechnology for instrumentation facilities.

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Nagasathiya Krishnan: conceptualization, formal analysis, project administration, resources, supervision, investigation, funding acquisition, validation, writing original draft preparation, and writing-reviewing and editing. Vairamani Mariappanadar: resources, data curation, validation, visualization, and writing-reviewing and editing. Anantha Krishnan Dhanabalan: resources, validation, visualization, and writing-reviewing and editing. Velmurugan Devadasan: data curation, validation, visualization, and writing-reviewing and editing. Subash C. B. Gopinath: validation, visualization, and writing-reviewing and editing. Pachaiappan Raman: data curation, methodology, visualization, validation, writing original draft preparation, and writing-reviewing and editing.

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Krishnan, N., Mariappanadar, V., Dhanabalan, A.K. et al. Purification, identification and in silico models of alkaloids from Nardostachys jatamansi — bioactive compounds for neurodegenerative diseases. Biomass Conv. Bioref. 13, 14889–14900 (2023). https://doi.org/10.1007/s13399-022-03237-y

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