Unveiling the effect ofWithania somniferaon neuronal cytoarchitecture and synaptogenesis: A combinedin vitroand network pharmacology approach

Abstract

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.

Differential Effects of the Processed and Unprocessed Garlic (Allium sativum L.) Ethanol Extracts on Neuritogenesis and Synaptogenesis in Rat Primary Hippocampal Neurons

“…Isofluorane was used to euthanize the rats, and the fetuses were collected on embryonic developmental day 19. The brains were dissected in order to obtain the hippocampal tissues, and the hippocampal neurons were prepared in the same manner as previously reported [10,45]. In brief, for morphometric analysis of early development, the cells were plated in 24-well plates with poly-DL-lysine (Sigma-Aldrich, St. Louis, MO, USA) coated coverslips and maintained in a specified serum-free neurobasal media supplemented with B27 and incubated at 37 • C with 5% CO 2 and 95% air.…”

“…Small molecule NTF mimetics have benefits over NTFs due to their accessibility to the blood-brain barrier [7]. As NTF mimetics, various medicinal herbs and their bioactive phytochemicals have emerged as a promising source of novel therapeutic agents for the treatment of neurodegenerative illnesses in recent years where the neurotrophic effects of these natural products have been linked to an increase in neuronal outgrowth [8][9][10][11]. Focusing on the neurotrophic effects of the bioactive components, the aim of this present study is to investigate the progression of neurons from the nascent neuronal differentiation stage to the synapse formation of the ethanol extract of unprocessed and processed A. sativum L.…”

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

“…The regulation of numerous receptors by W. somnifera bioactive substances was demonstrated using molecular docking, network pharmacology, and dynamic simulation‐based techniques to efficiently manage diverse neurological illnesses (Ahmad, Samuel, et al, 2016, Ahmad, Arya, et al, 2016, 2022; Shukla et al, 2022). In the same context, a further investigation was carried out using a combination of in vitro and in silico network pharmacology‐based methods (Mitra et al, 2022). There are multiple synthetic drugs made available for treating cancer.…”