morin and Brain-Ischemia

Cerebral damage following cerebral ischemia/reperfusion injury affects the neurological deficits and motor impairment of stroke patients in the long-term period. Angiogenesis, the essential process for restoration of cerebral blood flow (CBF) in the ischemic brain, promotes the recovery of neurological function following ischemia. The aim of this study was to investigate the long-term effects of morin on angiogenesis and functional outcomes in a middle cerebral artery occlusion (MCAO) and reperfusion model. Male Wistar rats were subjected to MCAO, and they were administered 30 mg/kg of morin at reperfusion via i.p. injection daily for 14 days. Fourteen days after I/R injury, the rats were evaluated for the brain damage, and angiogenic factors involved in Ang1/Tie-2 and Wnt/β-catenin signaling. In addition, at 1, 7, and 14 days after reperfusion, rotarod and pole tests were performed to investigate the functional recovery. We found morin significantly reduced the infarct size, blood-brain barrier (BBB) leakage, and apoptotic cells at 14 days after I/R injury. It also promoted angiogenesis via boosting the expression of angiogenic proteins, such as angiopoietin 1 (Ang1), Tie-2, Wnt3α, β-catenin, and cyclin D1. Morin-mediated angiogenesis was confirmed by a significant increase in microvessel's density in the penumbra area and an increase in von Willebrand factor (vWF) protein expression of the morin-treated rats. Moreover, the rotarod and pole tests also demonstrated morin increased functional recovery in the morin-treated rats compared to the vehicle rats. Therefore, our data exposed that morin promotes angiogenesis and improves functional outcomes in MCAO and reperfusion rats.

Topics: Angiopoietin-1; Animals; beta Catenin; Brain Ischemia; Flavonoids; Humans; Infarction, Middle Cerebral Artery; Male; Rats; Rats, Wistar; Reperfusion Injury

This study aimed to investigate the effects of morin on cerebral damage and blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) and reperfusion model. Wistar rats were exposed to MCAO for 2 h, followed by reperfusion. Thirty mg/kg of morin was administered via intraperitoneal injection at the different time points: before ischemia, during ischemia, and at reperfusion. The rats were divided into five groups, including sham, vehicle, and three groups of morin. Twenty-four hours after reperfusion, the rats were tested for neurological deficits, and the brains were harvested to assess brain damage. In addition, brains were harvested 72 h to determine BBB disruption. We found that morin significantly reduced reactive oxygen species production and lipid peroxidation. It also decreased inflammation via reducing the expression of Toll-like receptor 4, nuclear factor kappa-beta. Morin ameliorated cerebral damage and reduced apoptosis through decreasing the cerebral infarct size, including apoptotic cell death. Moreover, morin decreased the BBB damage via reducing Evans blue extravasation, neutrophil infiltration, and increasing tight junction protein expression. Therefore, morin protected against cerebral and BBB damage by attenuating oxidative stress, inflammation, and apoptosis in MCAO and reperfusion models.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Blood-Brain Barrier; Brain Ischemia; Disease Models, Animal; Flavonoids; Inflammation; Injections, Intraperitoneal; Lipid Peroxidation; Male; Neutrophil Infiltration; NF-kappa B; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Toll-Like Receptor 4

Morin is a flavanoid which exhibits potent antioxidant activity in various oxidative stress related diseases. The current study was attempted to scrutinize the preclinical bio-efficacy of morin on focal ischemia.. The animal model of focal cerebral ischemic injury was done by midbrain carotid artery occlusion (MCAO) method, followed by Morin (30mg/kg) administration for seven days.. The outcome of the study showed that treatment with morin displayed positive effects in reducing the focal cerebral ischemia. This effect was evident with the improvements in neurological deficits, reduction in MDA content and elevation of antioxidant levels (SOD, GSH and Gpx). Furthermore, protein expression of Bax and caspase-3 were effectively down-regulated, whilst the expression of Bcl-2 was significantly elevated. On the other hand, the mRNA expression of proinflammatory cytokines was significantly reduced in focal cerebral ischemic rats upon morin intervention.. Thus, the beneficial effects of morin on cerebral ischemia assault may result from the reduction of oxidative stress, inhibition of apoptosis and inflammation. The neuroprotective effects of morin supplement may serve as potent adjuvant in the amelioration of ischemic stroke.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Ischemia; Cytokines; Disease Models, Animal; Flavonoids; Inflammation; Male; Oxidative Stress; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley; RNA, Messenger; Stroke