Unveiling the effect of Withania somnifera on neuronal cytoarchitecture and synaptogenesis: A combined in vitro and network pharmacology approach.

Autor: Mitra S; Department of Anatomy, Dongguk University College of Medicine, Gyeongju, Republic of Korea., Munni YA; Department of Anatomy, Dongguk University College of Medicine, Gyeongju, Republic of Korea., Dash R; Department of Anatomy, Dongguk University College of Medicine, Gyeongju, Republic of Korea., Sultana A; Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh., Moon IS; Department of Anatomy, Dongguk University College of Medicine, Gyeongju, Republic of Korea.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2022 Jun; Vol. 36 (6), pp. 2524-2541. Date of Electronic Publication: 2022 Apr 20.
DOI: 10.1002/ptr.7466
Abstrakt: Withania somnifera (WS), is known for its remarkable contribution in herbal medicine and Ayurveda, which is therapeutically applied to improve memory and anxiety in patients. However, the pharmacological details of this plant on memory boosting yet remained undefined. This study provides mechanistic insights on the effect of ethanol solution extract of the whole plant of WS (WSEE) on neuritogenesis by combining in vitro and in silico network pharmacology approaches. WSEE promoted significant neuronal growth through early differentiation, axodendritic arborization, and synaptogenesis on primary hippocampal neurons. The network pharmacological study confirmed that the neuritogenic activity is potentially mediated by modulating the neurotrophin signaling pathway, where NRTK1 (TrkA) was revealed as the primary target of WS secondary metabolites. This neurotrophic activity of WSEE was significantly stifled by the presence of TrkA inhibitor, which further confirms the TrkA-dependent activity of WSEE. In addition, a molecular docking study suggested steroidal lactones present in the WS might act as nerve growth factor (NGF)-mimetics, activating TrkA by binding to the NGF-binding domain. As a whole, the findings of the study suggest a significant role of WSEE on neuritogenesis and its potential to function as a therapeutic agent and in drug designing for the prevention and treatment of memory-related neurological disorders.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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