Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation

Abstract

Background Systemic inflammation driven neuroinflammation is an event which correlates with pathogenesis of several neurodegenerative diseases. Therefore, targeting peripheral and central inflammation simultaneously could be a promising approach for the management of these diseases. Nowadays, herbal medicines are emerging as potent therapeutics against various brain pathologies. Therefore, in this contemporary study, the neuroprotective activity of Ashwagandha ( Withania somnifera ) was elucidated against the inflammation associated neurodegeneration and cognitive impairments induced by systemic LPS administration using in vivo rat model system. Methods To achieve this aim, young adult wistar strain male albino rats were randomized into four groups: (i) Control, (ii) LPS alone, (iii) LPS + ASH-WEX, (iv) ASH-WEX alone. Post regimen, the animals were subjected to Rotarod, Narrow Beam Walking and Novel Object Recognition test to analyze their neuromuscular coordination, working memory and learning functions. The rats were then sacrificed to isolate the brain regions and expression of proteins associated with synaptic plasticity and cell survival was studied using Western blotting and Quantitative real time PCR. Further, neuroprotective potential of ASH-WEX and its active fraction (FIV) against inflammatory neurodegeneration was studied and validated using in vitro model system of microglial conditioned medium–treated neuronal cultures and microglial-neuronal co-cultures. Results Orally administered ASH-WEX significantly suppressed the cognitive and motor-coordination impairments in rats. On the molecular basis, ASH-WEX supplementation also regulated the expression of various proteins involved in synaptic plasticity and neuronal cell survival. Since microglial-neuronal crosstalk is crucial for maintaining CNS homeostasis, the current study was further extended to ascertain whether LPS–mediated microglial activation caused damage to neurons via direct cell to cell contact or through secretion of inflammatory mediators. ASH-WEX and FIV pretreatment was found to restore neurite outgrowth and protect neurons from apoptotic cell death caused by LPS-induced neuroinflammation in both activated microglial conditioned medium–treated neuronal cultures as well as microglial-neuronal co-cultures. Conclusion This extensive study using in vivo and in vitro model systems provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.

Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management

“…WS leaf aqueous extract ameliorated inflammatory cytokine-induced neuroinflammation by inhibiting the NF-κB pathway in the rat model ( Gupta and Kaur, 2018 ). The same extract also showed a neuroprotective effect by normalizing MAP2 expression in microglial cells ( Gupta and Kaur, 2019 ). Therefore, this extract can be a promising candidate to prevent neuroinflammation.…”

Phytotherapy for treatment of cytokine storm in COVID-19

“…It was observed that after 8 weeks of administration, water extract of Ashawagandha ameliorated the inflammatory condition by suppressing the production of inflammatory cytokines viz. IL-1β, IL-6, and TNF-α by inhibiting Nuclear factor kappa B (NF-κB), P38 and mitogen activated protein kinase (MAPKs) signaling pathway [77,78]. WA treatment suppressed the activation of the nucleotide binding domain leucin rich repeat (NLRP3) inflammasome that further inhibited the IL-1β secretion in LPS induced macrophages and also suppressed the Helicobacter pylori stimulated production of IL-1β from dendritic cells by modulating NLRP-3 inflammasome and NF-κB activation in a dose dependent manner [79].…”

The role of nutraceutical fruit drink on neurodegenerative diseases: a review

“…Ageing remains an unavoidable and complex natural occurrence that can lead to the emergence of neurodegenerative diseases. It has been linked with a reduction in cognitive function which can significantly affect the quality of life (Gupta & Kaur, 2019). The term 'Nutraceutical' was derived from 'nutrition' and 'pharmaceutics'.…”