Diindolylmethane Ameliorates Ischemic Stroke-Induced Brain Injury by Peripheral and Central Mechanisms

Abstract

Introduction: Diindolylmethane (DIM), a major acid condensation product of Indole-3-carbinol, is known to inhibit platelet aggregation and thrombosis. The drugs with antiplatelet and antithrombotic activities are used to treat ischemic stroke. Objective: The present study investigated the role of DIM on platelet aggregation inhibitory properties in middle cerebral artery occluded (MCAO) rats. Methods: DIM (12.5, 25, and 50 mg/kg) was orally administered to MCAO rats for 3 days. Platelet aggregation, platelet cyclic adenosine monophosphate (cAMP), reactive oxygen species (ROS), hydrogen peroxide (H2O2), and serum cyclooxygenase (COX-1), thromboxane B2 (TXB2), and pros-taglandin E2 (PGE2), and inflammatory markers were estimated. Further brain structural and functional recovery was evaluated by measuring cerebral blood flow, neurological deficits, brain infarction, blood-brain barrier (BBB) leakage, brain water content, and histological abnormalities. Results: DIM significantly ameliorated adenosine diphosphate (ADP), collagen, thrombin, and ara-chidonic acid-induced platelet aggregation by inhibiting COX-1, TXB2, and PGE2 and elevating cAMP. Further, DIM also alleviated platelet-mediated oxidative stress (ROS and H2O2) and reduced the serum inflammatory markers, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and increased anti-inflammatory cytokine, IL-10, in MCAO rats. Conclusion: DIM treatment confers neuroprotection in MCAO rats by inhibition of platelet aggre-gation, platelet-mediated oxidative stress, and inflammation. Correspondingly, DIM improved cerebral blood flow and reduced neurological deficits, brain infarction, BBB leakage, brain water con-tent, and histopathological abnormalities indicating the preservation of brain structural integrity. Thus, the present study provided preclinical evidence of DIM neuroprotection against ischemic stroke. © 2022 Bentham Science Pub.