Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke

Abstract

Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model

“…Interestingly, pre-treatment of SH-SY5Y cells with KSM-66 followed by 6-OHDA treatment was able to lower protein glutathionylation within the cells ( Figure 7 ). These results are in agreement with earlier reports on Ashwagandha extract mediated inhibition of glutathionylation formation in in vitro and in vivo studies ( Sood et al., 2018 ; Vidyashankar et al., 2014 ). It has been reported that a mechanism for Ashwagandha protection of neuronal cells was through activation of the Nrf2 pathway ( Hybertson et al., 2019 ; Priyandoko et al., 2011 ).…”

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics

“…Withaferin A is a component of Withania somnifera ( ashwagandha or Indian ginseng ) ( Srivastava et al, 2020 ). W. somnifera has been used in traditional medicine as an antioxidant, antianxiety, anti-inflammatory, antibacterial, aphrodisiac, and herbal tonic for general health ( Sood et al, 2018 ). The active ingredients include withanolides, saponins, alkaloids, and steroidal lactones.…”

“…Adjunctive treatment with ashwagandha improved symptoms and stress in patients with schizophrenia, offering beneficial effects on cognitive function in patients with bipolar disorder and improves balance in patients with progressive degenerative cerebral ataxias ( Sood et al, 2018 ; Singh et al, 2021 ). It was recently shown that withanolides present in ashwagandha possess anti-COVID-19 properties , and these compounds exhibit good absorption and transport kinetics with no related mutagenic or adverse effects ( Srivastava et al, 2020 ).…”

Deciphering Novel SARS CoV-2 specific Disease Pathways from RNA Sequencing Data of COVID-19 Infected A549 Cells and Potential Therapeutics using Next Generation Knowledge Discovery Platforms

“…The active ingredients mainly include withanolides, saponins, alkaloids, and steroidal lactones. W. somnifera is used in herbal formulations in traditional medicine possess antioxidant, anti-anxiety, anti-in ammatory, anti-bacterial, and aphrodisiac properties, etc (Sood et al, 2018). Ashwagandha has neuroprotective, cardioprotective, immunomodulating, and anti-cancer properties (Singh et al, 2021).…”