luteolin-7-glucoside and Infarction--Middle-Cerebral-Artery

Galuteolin, a Chinese herbal medicine, purified from Lonicera Japonica. In this study, we aimed to investigate the neuroprotective effect of galuteolin against cerebral ischemia/reperfusion (I/R) injury. We administered galuteolin or galuteolin and rapamycin to rats which had middle cerebral artery occlusion/reperfusion (MCAO/R). A series of characterizations were carried out to monitor the outcomes of galuteolin in I/R rats regarding the infarct volumes, neurological deficits, and brain water, as well as its effect on neuroprotection and autophagy. It was found that galuteolin significantly reduced the infarct volume, brain water content, and the neurological deficits in a dose-dependent manner. Neuron damages were decreased in the hippocampal carotid artery 1 pyramidal layer by galuteolin. The expression levels of neuron-specific enolase (NSE) increased after galuteolin treatment. Galuteolin significantly decreased the expression levels of autophagy-related proteins. In addition, galuteolin decreased rapamycin-related neuron damages and activations of autophagy in I/R rats. Our data suggested that galuteolin can inhibit ischemic brain injuries through the regulation of autophagy-related indicators in I/R.

Topics: Animals; Autophagy; Body Water; Cerebral Infarction; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Glucosides; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Luteolin; Male; Molecular Structure; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sirolimus

Luteoloside, a flavonoid compound, has been reported to have anti-inflammatory, anti-oxidative, antibacterial, antiviral, anticancer, and cardioprotective effects, among others, but its neuroprotective effects have rarely been studied. The purpose of this study was to investigate the protective effect of luteoloside on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of luteoloside on cerebral ischemia-reperfusion (I/R). Male Sprague-Dawley rats were randomly divided into six groups: sham, MCAO, luteoloside (20 mg/kg, 40 mg/kg, 80 mg/kg) and nimodipine (4 mg/kg). The results showed that luteoloside alleviated neurologic deficits and cerebral edema as well as improved cerebral infarction and histopathological changes in MCAO rats. Luteoloside significantly inhibited I/R-induced neuroinflammation, as demonstrated by reduced levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the brain tissues of MCAO rats. Furthermore, our results demonstrated that luteoloside significantly suppressed the activation of nuclear factor-kappa B (NF-κB) signaling, upregulated the protein expression of peroxisome proliferator activated receptor gamma (PPARγ) and increased NF-E2-related factor (Nrf2) nuclear accumulation in MCAO rats. Collectively, our findings suggested that luteoloside played a crucial neuroprotective role by inhibiting NF-κB signaling in focal cerebral ischemia in rats. Furthermore, PPARγ and Nrf2 were also important for the anti-inflammatory effect of luteoloside. In addition, our data suggested that luteoloside might be an effective treatment for cerebral ischemia and other neurological disorders.

Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Cells, Cultured; Cyclooxygenase 2; Disease Models, Animal; Glucosides; Humans; Infarction, Middle Cerebral Artery; Interleukin-1beta; Luteolin; Male; Neurogenic Inflammation; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; PPAR gamma; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha