Ameliorative Effect of <b><i>Withaferin</i></b> <b><i>A</i></b> on Ageing-Mediated Impairment in the Dopamine System and Its Associated Behavior of Wistar Albino Rat

Abstract

Withaferin A (WA) was evaluated for its neuro-protective efficacy on ageing induced striatal dopamine (DA) and behavioural changes in aged rats. Wistar albino rats were divided into group I – young (3 months), Group II – aged (24 months), Group III – aged rats supplemented with WA (50 mg/kg b.w once in a day for 30 days) and Group IV – young rats supplemented with WA (50 mg/kg b.w). The HPLC assay revealed significant decline in the levels of DA and homovanillic acid (HVA) in substantia nigra (SN) and striatum (ST) of aged rat. A marked decline in motor activity of aged rat was observed through open field, beam walking and grid walking motor experiments. These results indicate that ageing reduces nigro-striatal activity as well as nigro-striatal DA levels. Interestingly, the administration of WA (50 mg\kg b.w) resulted in a substantial resurge of DA and HVA in SN and ST and a significant reversal of motor impairment in aged rats. This study is the first report that evidently determines the neuro-protective efficacy of WA on dopaminergic system of SN and ST in aged rats.

Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera

“…WA decreased the signal mediated by the chemokines and cytokines, and also attenuated TGFβ along with the downstream signalling molecule resulting in the inhibition of expression of GF-β1, TGF-β2, p-Smad2, p-Smad3, total Smad4, p-Akt and p-ERK. Banu et al (2019aBanu et al ( , 2019b's study evaluated the efficacy of WA on ageing induced oxidative stress in substantia nigra (SN-a basal ganglia structure that is located in the midbrain; it plays a relevant role in movement) and striatum of Wistar rats; 50 mg/kg/day dose was given for 30 days, to both aged and young rats. In aged rats, there is observed reduced enzymatic antioxidant, increase in the reactive oxygen species, increased caspase activity and increased apoptotic nuclear morphology compared to the young rats.…”

“…Notably, WA significantly reduced the activation of the NLRP3 inflammasome. Banu et al (2019aBanu et al ( , 2019b evaluated the neuroprotective effect of WA on the behavioural changes in aged rats and ageing induced striatal dopamine (DA); to both groups, 50 mg/kg dose was administered (to the young and aged rats); the other two groups were included, aged and young rats, without WA administration. HPLC assay was used for the measurement of dopamine and homo vanillic acid in substantia nigra and striatum of aged rats.…”