Isoquercitrin Upregulates Aldolase C Through Nrf2 to Ameliorate OGD/R-Induced Damage in SH-SY5Y Cells.

Isoquercitrin (ISO), an extract from Chinese traditional herb, exhibits potent neuroprotective roles in various disease models. However, its role in stroke is not fully understood. We established oxygen-glucose deprivation and reoxygenation (OGD/R) model in SH-SY5Y cell to study the roles of ISO in stroke. In the experiment, the changes of LDH level and cell viability (MTT) were analyzed. Apoptotic cells stained with anti-Annexin V antibody and propidium iodide (PI) were detected by flow cytometry. The mRNA and protein level of aldolase C (ALDOC) and nuclear factor erythroid 2-related factor (Nrf2) was determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting assay, respectively. The localization of Nrf2 was investigated by immunofluorescent assay. OGD/R reduced cell viability via inducing cell apoptosis, while ISO treatment reduced the level of apoptosis in OGD/R-treated SH-SY5Y cells ISO rescued OGD/R-treated cells. Mechanistically, the expression of Nrf2 and ALDOC was upregulated upon ISO treatment, while knockdown of ALDOC diminished the activation of autophagy and hence inhibited ISO-mediated protective activity. We further demonstrated that ISO enhanced ALDOC transcription by promoting nuclear translocation of Nrf2, and suppression of Nrf2 decreased the expression of ALDOC. Our data revealed that ISO exhibited neuroprotective activity in OGD/R model through Nrf2-ALDOC-autopagy axis and highlighted the potential application of ISO in stroke treatment.

Black Bamboo Rhizome Extract Improves Cognitive Dysfunction by Upregulating the Expression of Hippocampal BDNF and CREB in Rats with Cerebral Ischaemia-Reperfusion Injury.

INTRODUCTION: The study aimed to explore the effects of treatment with black bamboo rhizome extracts on learning and memory and determine the underlying mechanisms in rats with cerebral ischaemia-reperfusion injury. METHODS: Sprague-Dawley rats were randomly divided into the following four groups: control, middle cerebral artery occlusion (MCAO), low-dose drug, and high-dose drug groups. Rats underwent MCAO using a suture method before drug treatment. Then, neurological impairment was assessed using the Longa scoring method, and triphenyl tetrazolium chloride staining was used to analyse the cerebral infarction area. The Elliott formula was used to calculate water content in the brain tissue. A Morris water maze (MWM) was used to assess changes in learning and memory abilities, and Western blotting was used to detect cyclic adenosine phosphate response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of MCAO rats. RESULTS: After treatment with black bamboo rhizome extracts, the neurological dysfunction score was lower in the drug groups than in the MCAO group, and a significant difference was observed between the high-dose drug and MCAO groups (P<0.05). Additionally, the cerebral infarction area was significantly smaller in the drug groups than in the MCAO group (P<0.01), and the effect was more obvious in the high-dose drug group than in the low-dose drug group. There was also a significant difference in water content between the high-dose drug and MCAO groups, and cerebral oedema was significantly reduced in the high-dose drug group (P<0.05). In the MWM, the incubation period was significantly reduced, the number of platform crossings was significantly increased, and the search time was prolonged in the drug groups compared with those in the MCAO group (P<0.05). Moreover, the expression of BDNF and CREB was significantly increased in the drug groups compared to that in the MCAO group, and the increase was more obvious in the high-dose group than in the low-dose group (P<0.05). DISCUSSION: Black bamboo rhizome extracts significantly improved cognitive dysfunction, reduced cerebral oedema, decreased the cerebral infarction area, and improved the neurological function score and learning and memory abilities in rats with cerebral ischaemia-reperfusion injury.

Neuroprotection by 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside extracts from Polygonum multiflorum against cerebral ischemia/reperfusion injury through the 5-hydroxytryptamine/5-hydroxytryptamine receptor pathway.

Objective: To investigate the therapeutic effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) on the expression of 5-hydroxytryptamine (5-HT)/5-HT receptor 2A (5-HT2A), 5-HT transporter (5-HTT), and uncoupling protein 4 (UCP4) after cerebral ischemia/reperfusion (I/R) injury. Methods: Sprague-Dawley rats were randomly divided into control, model and 125 (low-dose), 250 (middle-dose), and 500 (high-dose) mg/mL TSG groups. Rat cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO). After successful establishment of rat MCAO model, rats in control and model groups were decapitated immediately. Rats in TSG group were orally administered 125, 250, and 500 mg/mL TSG in corresponding groups at a dose of 1 mL/100 g per day for 7 continuous days, and then the rats were decapitated. The infarct size was determined using triphenyl tetrazolium chloride staining and the expression of UCP4 and 5-HT2A in the hippocampus and thalamic nucleus was detected using immunohistochemistry and western blot assay. The expression of 5-HTT in brain tissue was detected using western blot assay. Serum 5-HT levels were detected using ELISA. Results: After treatment, the infarct size due to cerebral I/R injury decreased with increased concentrations of TSG. Synchronous reduction of 5-HT in the blood and 5-HTT in the brain was observed, and 5-HT2A was expressed in normal brain tissue but its level was increased in rats after cerebral I/R injury. A high level of UCP4 was found in normal brain tissue, which rose by 6 hrs after cerebral I/R injury but reduced to minimal levels 24 hrs after injury. With increasing TSG concentration, the levels of 5-HT, 5HTT, and UCP4 were increased, while the level of 5-HT2A was decreased. Conclusion: TSG is effective in treating cerebral I/R injury in rats, and its mechanism may be implemented through the 5-HT/5-HTR pathway, by increasing 5-HT release, enhancing the activity of 5-HTT, increasing expression of UCP4, and inhibiting 5-HT2A activity.