scutellarein and Brain-Ischemia

Topics: Animals; Apigenin; Brain Ischemia; Disease Models, Animal; Infarction, Middle Cerebral Artery; Neurons; Neuroprotective Agents; PC12 Cells; Pyrazines; Rats; Reperfusion Injury; Stroke

Scutellarin (

Topics: Animals; Antioxidants; Apigenin; Biphenyl Compounds; Brain Ischemia; Cerebrovascular Disorders; Chromans; Erigeron; Fibrinolytic Agents; Free Radical Scavengers; Glucuronates; Humans; Male; Picrates; Rabbits; Solubility

Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 -induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.

Topics: Animals; Anticoagulants; Antioxidants; Apigenin; Brain Ischemia; Drug Design; Drug Evaluation, Preclinical; Neuroprotective Agents; PC12 Cells; Rats

For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

Topics: Animals; Apigenin; Brain Ischemia; Drugs, Chinese Herbal; Glucuronates; Male; Metabolome; Metabolomics; Neuroprotective Agents; Rats; Rats, Wistar

Scutellarin had protective effects against neuronal injury, however, there are few studies on the protective effect of scutellarein, which is the main metabolite of scutellarin in vivo. This study investigated whether the neural injury by ischemia/reperfusion would be influenced by different doses of scutellarin and scutellarein. Male Wistar rats were orally administered with scutellarin and scutellarein at the doses of 0.09, 0.17, 0.35, 0.70, 1.40 mmol/kg, respectively; then after six consecutive days, they were subjected to global ischemia by occlusion of the bilateral common carotid arteries (BCCAO). After reperfusion for about 21 h, neurological and histological examinations were performed. The present results showed that scutellarein attenuated neuronal cell damage, reduced cerebral water content, regulated the expression of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), γ-aminobutyric acid (GABA) and taurine (Tau), and improved the Ca(2+)-ATPase and Na(+),K(+)-ATPase activity. Meanwhile, significant difference was found among various doses of scutellarin and scutellarein. Our studies indicated that scutellarin and scutellarein could improve neuronal injury, and scutellarein had better protective effect than scutellarin in rat cerebral ischemia.

Topics: Amino Acids; Animals; Antioxidants; Apigenin; Brain; Brain Injuries; Brain Ischemia; CA1 Region, Hippocampal; Calcium; Calcium-Transporting ATPases; Glucuronates; Learning; Male; Memory; Neuroprotective Agents; Nimodipine; Potassium; Rats; Rats, Wistar; Reperfusion Injury; Sodium; Sodium-Potassium-Exchanging ATPase

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO) with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.

Topics: Animals; Apigenin; Brain Ischemia; Glucuronates; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Rats; Reperfusion Injury

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.

Topics: Animals; Brain Ischemia; Flavanones; Flavonoids; Hippocampus; Male; Neuroprotective Agents; Nitric Oxide; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha