Neuritic regeneration and synaptic reconstruction induced by withanolide A

Abstract

1 We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. 2 Treatment with Ab(25-35) (10 mM) induced axonal and dendritic atrophy, and pre-and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 mM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre-and postsynapses in the neurons. 3 WL-A (10 mmol kg À1 day À1 , for 13 days, p.o.) recovered Ab(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. 4 WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.

Estimation of antioxidant potential of individual components present in complex mixture ofWithania somnifera(Ashwagandha) root fraction by thin-layer chromatography-2,2-diphenyl-1-picrylhdrazyl method

“…The intensity of peak was estimated by ImageJ software; values are summarized in Table 2. WF A, WN A, WS V, WNN, and 1,2-DWM are biologically active, and among all these, WF A and WN A are potent [38][39][40][41][42][43][44][45]; from the present study, we also observed the same results. WF A has the highest antioxidant activity followed by WN B, WN A, WS V, 1,2-DWM, and WNN, respectively, while in unknown components, peak No.…”

Withanolides and Related Steroids

“…Withanoside IV (31) and VI (32) predominantly induced dendritic outgrowth in normal cortical neurons, while withanolide A (504) predominantly induced axon outgrowth (262). These withanolides also showed neuritic regeneration and synaptic reconstruction of damaged cortical neurons and prevented both dendritic and axonal atrophy induced by Ab (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) (261,263). Oral administration of withanoside IV significantly improved memory deficit in Ab(25-35) treated mice, and sominone, the aglycone of withanoside IV, was shown to be the major metabolite after administration.…”

Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster

“…WS root extract and withanoside VI were shown to possess inhibitory action on acetylcholinesterase activity in both in vivo and in vitro (Choudhary et al 2005). Further, evidences suggest the protective effect of WS root extract and its constituents on presynaptic and post-synaptic neurons in animal models of dementia and spinal cord injury (Kuboyama et al 2005). A polyherbal preparation, BR-16 (Mentat®), which includes WS as one of the major component exhibited significant protective effect against reserpine-induced catalepsy in mice (Kumar and Kulkarni 2006).…”