lignans and Cerebral-Hemorrhage

Polyphenols are an important family of molecules of vegetal origin present in many medicinal and edible plants, which represent important alimentary sources in the human diet. Polyphenols are known for their beneficial health effects and have been investigated for their potential protective role against various pathologies, including cancer, brain dysfunctions, cardiovascular diseases and stroke. The prevention of stroke promoted by polyphenols relies mainly on their effect on cardio- and cerebrovascular systems. However, a growing body of evidence from preclinical models of stroke points out a neuroprotective role of these molecules. Notably, in many preclinical studies, the polyphenolic compounds were effective also when administered after the stroke onset, suggesting their possible use in promoting recovery of patients suffering from stroke. Here, we review the effects of the major polyphenols in cellular and in vivo models of both ischemic and hemorrhagic stroke in immature and adult brains. The results from human studies are also reported.

Topics: Animals; Brain Ischemia; Cerebral Hemorrhage; Diarylheptanoids; Ellagic Acid; Flavonoids; Gastrointestinal Microbiome; Humans; Hydrolyzable Tannins; Hydroxybenzoates; Lignans; Polyphenols; Stilbenes; Stroke; Subarachnoid Hemorrhage

Intracerebral haemorrhage (ICH) induces inflammation, which can cause severe secondary injury. Recent evidence has suggested that magnolol (MG) has a protective effect against ischaemic stroke through the inhibition of inflammation. However, the anti-inflammatory effect of MG in intracerebral haemorrhage (ICH) remains unclear. Here, we report that the protective effect of MG in a rat model of ICH can be achieved by anti-inflammatory processes. We found that MG administration significantly reduced the brain water content, restored the blood-brain barrier (BBB) and subsequently attenuated neurological deficits via decreasing the activation of glial cells, decreasing the infiltration of neutrophils and reducing the production of pro-inflammation factors (IL-1β, TNF-α and MMP-9) in a rat model of ICH. These results suggest that MG reduced inflammatory injury and improved neurological outcomes in ICH model.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Biphenyl Compounds; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Cerebral Hemorrhage; Cytokines; Disease Models, Animal; Inflammation; Lignans; Male; Neuroglia; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Stroke

Thrombin plays important roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MAPK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 μM) suppressed thrombin-induced nitric oxide (NO) production by primary-cultured rat microglia via inhibition of inducible NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MAPK phosphorylation in the MAPK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model was prepared by intrastriatal injection of 0.20U collagenase type IV unilaterally. ICH evoked the phosphorylation of p44/42 MAPK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The phosphorylation of p44/42 MAPK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MAPK pathway in ICH.

Topics: Animals; Antioxidants; Brain; Cell Death; Cell Proliferation; Cells, Cultured; Cerebral Hemorrhage; Dioxoles; Disease Models, Animal; Lignans; Male; MAP Kinase Signaling System; Microglia; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neurons; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Rats, Sprague-Dawley; Rats, Wistar