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

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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.

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Abbreviations

WS :

Withania somnifera

IRI:

Ischemia reperfusion injury

Bcl-2:

B-cell lymphoma 2

Bax:

Bcl-2-associated X-protein

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Acknowledgements

The authors acknowledge the financial assistance received from the University Grants Commission (New-Delhi) under Basic Science Research (BSR) scheme-Special Assistance Programme (SAP) and Department of Science and Technology (DST, New-Delhi) under DST-FIST Programme. Authors also acknowledge Dabur India Private Limited (Ghaziabad, India) for providing hydro-alcoholic root extract of WS for research purpose.

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Authors and Affiliations

  1. Department of Biochemistry, Panjab University, Chandigarh, 160014, India

    Abhilasha Sood, Arpit Mehrotra & Rajat Sandhir

  2. CSIR-Institute of Microbial Technology, Chandigarh, 160036, India

    Arpit Mehrotra

  3. Department of Biophysics, Panjab University, Chandigarh, 160014, India

    Devinder K. Dhawan

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  1. Abhilasha Sood
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  2. Arpit Mehrotra
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Correspondence to Rajat Sandhir.

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Sood, A., Mehrotra, A., Dhawan, D.K. et al. Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke. Metab Brain Dis 33, 1261–1274 (2018). https://doi.org/10.1007/s11011-018-0234-2

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