Noscapine alleviates cerebral damage in ischemia-reperfusion injury in rats
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ORIGINAL ARTICLE
Noscapine alleviates cerebral damage in ischemia-reperfusion injury in rats Manisha Kawadkar 1 & Avinash S. Mandloi 1 & Vidhu Saxena 1 & Chetana Tamadaddi 2 & Chandan Sahi 2 & Vipin V. Dhote 1 Received: 15 May 2020 / Accepted: 15 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract With high unmet medical needs, stroke remains an intensely focused research area. Although noscapine is a neuroprotective agent, its mechanism of action in ischemic-reperfusion (I-R) injury is yet to be ascertained. We investigated the effect of noscapine on the molecular mechanisms of cell damage using yeast, and its neuroprotection on cerebral I-R injury in rats. Yeast, both wild-type and Δtrx2 strains, was evaluated for cell growth and viability, and oxidative stress to assess the noscapine effect at 8, 10, 12, and 20 μg/ml concentrations. The neuroprotective activity of noscapine (5 and 10 mg/kg; po for 8 days) was investigated in rats using middle cerebral artery occlusion-induced I-R injury. Infarct volume, neurological deficit, oxidative stress, myeloperoxidase activity, and histological alterations were determined in I-R rats. In vitro yeast assays exhibited significant antioxidant activity and enhanced cell tolerance against oxidative stress after noscapine treatment. Similarly, noscapine pretreatment significantly reduced infarct volume and edema in the brain. The neurological deficit was decreased and oxidative stress biomarkers, superoxide dismutase activity and glutathione levels, were significantly increased while lipid peroxidation showed significant decrease in comparison to vehicle-treated I-R rats. Myeloperoxidase activity, an indicator of inflammation, was also reduced significantly in treated rats; histological changes were attenuated with noscapine. The study demonstrates the protective effect of noscapine in yeast and I-R rats by improving cell viability and attenuating neuronal damage, respectively. This protective activity of noscapine could be attributed to potent free radical scavenging and inhibition of inflammation in cerebral ischemia-reperfusion injury. Keywords Yeast . Middle cerebral artery occlusion . Inflammation . Antioxidant . Ischemia-reperfusion injury
Abbreviations tPA Tissue plasminogen activator FDA Food and Drug Administration MCAO Middle cerebral artery occlusion I-R Ischemia-reperfusion H2O2 Hydrogen peroxide YPD Yeast extract, peptone, dextrose WT Wild type Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00210-02002005-x. * Vipin V. Dhote [email protected]; [email protected] 1
Department of Pharmacology, Faculty of Pharmacy, VNS Group of Institutions, VidyaVihar, Neelbud, Bhopal, Madhya Pradesh 462044, India
2
Chaperone and Stress Biology Lab, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India
TRX2 ROS NOS SOD GSH LPO MPO BBB TTC DTNB TCA MDA EB
Thioredoxin-2 Reactive oxygen species Noscap
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