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Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment

Abstract

Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment.

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Acknowledgments

The authors thank the Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH), Ministry of Health and Family Welfare, Government of India, New Delhi, for the financial assistance. The technical assistance of Dharamvir Singh and Abdul Fitr are greatly acknowledged. We greatly acknowledge Dr. Amrish Kumar Tiwari (M.V.Sc. Pathology), Jamia Hamdard, India for the histological interpretation for this manuscript.

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The authors have no conflict of interest.

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Correspondence to Fakhrul Islam.

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Fund for the Improvement of Science and Technology was sponsored by DST and Special Assistance Programme was sponsored by UGC.

Handling Editor: Pavel Dráber

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Ahmed, M.E., Javed, H., Khan, M.M. et al. Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment. Protoplasma 250, 1067–1078 (2013). https://doi.org/10.1007/s00709-013-0482-2

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Keywords

  • Antioxidant
  • Cognitive impairment
  • Oxidative stress
  • Streptozotocin
  • Withania somnifera