Abstract
Stroke is one of the most common causes of death worldwide and also responsible for permanent disability. Ischemic stroke has been found to affect 80% of stroke patients. Recombinant tissue plasminogen activator (rtPA) is the widely used drug for the ischemic stroke with narrow therapeutic window. Indole-3-carbinol (I3C) is a natural compound obtained from brassica species having antithrombotic activity. Middle cerebral artery occlusion (MCAO) model was used followed by reperfusion after 2 h of ischemia for the evaluation of the I3C against ischemic stroke. After reperfusion, I3C (12.5, 25, and 50 mg/kg) was given by oral route once daily and continued up to the 14th day. Behavioral studies including postural reflex, forelimb placing, and cylinder tests showed I3C attenuated the MCAO-induced increase in average score and asymmetry score efficiently. Mean cerebral blood flow (CBF) was improved by treatment with I3C (12.5 mg/kg) by 60% of baseline at 6 h. I3C inhibited ADP-induced platelet aggregation and reduced ischemic volume significantly. It also inhibited in vitro the ADP-induced platelet aggregation in healthy human volunteers. I3C improves behavioral scores and mean CBF after focal cerebral ischemia in rats. Furthermore, I3C showed prophylactic anti-thrombotic activity against carrageenan induced tail thrombosis. Therefore, preclinical evidence points to I3C as a potential candidate for use in cerebral ischemic stroke.
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This work was supported by the teaching assistantship to Pankaj Paliwal from Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, U.P., India.
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P.P, G.C and S.K are inventors of an Indian patent application “An Oral Composition of Indole-3-Carbinol and A Method of Preparation Thereof” (No. 201711026941, 28/July/2017). All other authors declare no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Ethics Committee, Institute of Medical Sciences, Banaras Hindu University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Ethics Committee at which the studies were conducted (Protocol no. Dean/2016/CAEC/31).
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Paliwal, P., Chauhan, G., Gautam, D. et al. Indole-3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model. Naunyn-Schmiedeberg's Arch Pharmacol 391, 613–625 (2018). https://doi.org/10.1007/s00210-018-1488-2
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DOI: https://doi.org/10.1007/s00210-018-1488-2