isoquercitrin and Ischemia

Ischemic stroke is a major disability and cause of death worldwide due to its narrow therapeutic time window. Neuroprotective agent is a promising strategy to salvage acutely ischemic brain tissue and extend the therapeutic time window for stroke treatment. In this study, we aimed to evaluate the neuroprotective effects of isoquercetin in (1) primary culture of rat hippocampal neurons exposure on oxygen and glucose deprivation and reperfusion (OGD/R) injury and (2) rats subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R) injury. The results showed that isoquercetin post-treatment reduced the infarct size, number of apoptotic cells, oxidative stress, and inflammatory response after ischemia and reperfusion injury. The underlying mechanism study indicated that the neuroprotective effects of isoquercetin were elicited via suppressing the activation of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and caspase-1; the phosphorylation of ERK1/2, JNK1/2, and p38 mitogen-activated protein kinase (MAPK); and the secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. In addition, isoquercetin also effectively alleviated hippocampus neuron apoptosis by regulation of cyclic AMP responsive element-binding protein (CREB), Bax, Bcl-2, and caspase-3. Our report provided new considerations into the therapeutic action and the underlying mechanisms of isoquercetin to improve brain injury in individuals who have suffered from ischemic stroke. As a potent anti-inflammatory and anti-oxidative compound with neuroprotective capacities, the beneficial effects of isoquercetin when used to treat ischemic stroke and related diseases in humans warrant further studies.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Brain Ischemia; CA1 Region, Hippocampal; Cells, Cultured; Inflammation; Ischemia; Male; Neurons; Neuroprotective Agents; Oxidative Stress; Quercetin; Rats, Sprague-Dawley; Reperfusion Injury

Dietary flavonoid intake shows a significant inverse association with mortality from coronary heart disease, incidence of myocardial infarction and stroke. Quercetin is one of the most common flavonoids in our diet and has several favorable biological activities. Quercetin glucosides, which are enzymatically trans-glycosylated isoquercitrin, have high water-solubility and bioavailability compared with quercetin. Here, we investigated the effects of quercetin glucosides on collateral development in a murine hindlimb ischemia model.. We induced hindlimb ischemia in 24- to 32-week-old male C3H/HeJ mice by resecting the right femoral artery. Then, 0.5% carboxymethyl cellulose (control) or quercetin glucosides (100mg/kg/day) were administered daily by gavage. Blood flow was monitored weekly by laser Doppler imaging.. Recovery of blood flow to the ischemic leg was significantly enhanced by quercetin glucosides (blood flow ratio at 4 weeks: control, 0.57 ± 0.11; quercetin glucosides, 0.95 ± 0.10, p<0.05). Furthermore, anti-CD31 immunostaining revealed that quercetin glucosides increased capillary density in the ischemic muscle (control, 200 ± 24/mm(2); quercetin glucosides, 364 ± 41/mm(2), p<0.01). Quercetin glucosides did not promote tumor growth. The beneficial effect of quercetin glucosides was abrogated in eNOS-deficient mice.. These results suggest that quercetin glucosides may have therapeutic potential to promote angiogenesis in ischemic tissue.

Topics: Angiogenesis Inducing Agents; Animals; Antioxidants; Capillaries; Cytokines; Disease Models, Animal; Glucosides; Hindlimb; Ischemia; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Mutant Strains; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; Quercetin