Abstract
Global cerebral ischemia/reperfusion (I-R) injury often results in an irreparable brain damage like behavioral impairment and neuronal death. This neurological complication involves diverse intricate pathological mechanisms like oxidative stress, inflammation, and apoptosis. Recently, the therapeutic value of plant-based polyphenols has gained researcher’s attention. The present study focused on the putative neuroprotective role of negundoside on behavioral and oxidative stress status in an experimental model of global cerebral ischemia and reperfusion-induced brain injury. Negundoside was isolated from the leaves of Vitex negundo Linn. by chromatography for investigating its possible neurobehavioral and neuropharmacological implications. Healthy Balb/C mice of either sex were subjected to 10 min of global cerebral ischemia (GCI) followed by 24-h reperfusion. Mice were pre-treated intraperitoneally with negundoside at varying doses (1, 3, 5, 10, and 15 mg/kg) 60 min before the induction of GCI. Mice were later subjected to a battery of behavioral tests for evaluating memory-related and motor abilities. Elevated plus maze (EPM) was used to determine the anxiety levels and short-term memory whereas motor abilities were evaluated by inclined beam-walking test, rotarod, and lateral push test. TBARS and reduced glutathione (GSH) content in brains were analyzed spectrophotometrically as oxidative stress markers. Behavioral study revealed enhanced anxiety-related responses and motor deficits in I-R injured mice. Additionally, GSH and TBARS levels were found to be altered following I-R-induced neuronal injury. Contrastingly, negundoside administration was able to alleviate the behavioral and biochemical alterations to the normal levels. Together, our findings provide preliminary evidence of neuroprotective role of negundoside against global cerebral ischemia and reperfusion-induced behavioral dysfunction and oxidative damage in mice brain.
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Acknowledgements
We duly acknowledge the generous support provided by Dr. K.A. Suri, the Chairman of the Instrumentation Division of the Indian Institute of Integrative Medicine (IIIM), CSIR, Jammu-Tawi for providing a laboratory space to conduct fingerprinting of the isolated Negundoside and to carry out the present investigation.
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Kamakshi Mehta and Deepak Prabhakar Bhagwat share equal first authorship.
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Mehta, K., Bhagwat, D.P., Devraj et al. Vitex negundo protects against cerebral ischemia–reperfusion injury in mouse via attenuating behavioral deficits and oxidative damage. Psychopharmacology 239, 573–587 (2022). https://doi.org/10.1007/s00213-021-06050-z
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DOI: https://doi.org/10.1007/s00213-021-06050-z