1-1-diphenyl-2-picrylhydrazyl and Ischemia

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, it is very difficult to obtain scutellarein in nature compared with scutellarin. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. The in vitro antioxidant activities of scutellarein were evaluated by measuring its scavenging capacities toward DPPH, ABTS(+•), (•)OH free radicals and its protective effect on H(2)O(2)-induced cytotoxicity in PC12 cells using MTT assay method. The results showed that essential point to the synthesis was the implementation of H(2)SO(4) in 90% ethanol in N(2) atmosphere; scutellarein had stronger antioxidant activity than scutellarin. The results have laid the foundation for further research and the development of scutellarein as a promising candidate for ischemic cerebrovascular disease.

Topics: Animals; Apigenin; Benzothiazoles; Biphenyl Compounds; Cell Survival; Cerebrovascular Disorders; Free Radical Scavengers; Glucuronates; Hydrogen Peroxide; Ischemia; PC12 Cells; Picrates; Rats; Sulfonic Acids

The neuroprotective effects of minocycline-which is broadly protective in neurologic-disease models featuring cell death and is being evaluated in clinical trials-were investigated both in vitro and in vivo. For the in vivo study, focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice. Minocycline at 90 mg/kg intraperitoneally administered 60 min before or 30 min after (but not 4 h after) the occlusion reduced infarction, brain swelling, and neurologic deficits at 24 h after the occlusion. For the in vitro studies, we used cortical-neuron cultures from rat fetuses in which neurotoxicity was induced by 24-h exposure to 500 microM glutamate. Furthermore, the effects of minocycline on oxidative stress [such as lipid peroxidation in mouse forebrain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. Minocycline significantly inhibited glutamate-induced cell death at 2 microM and lipid peroxidation and free radical scavenging at 0.2 and 2 microM, respectively. These findings indicate that minocycline has neuroprotective effects in vivo against permanent focal cerebral ischemia and in vitro against glutamate-induced cell death and that an inhibition of oxidative stress by minocycline may be partly responsible for these effects.

Topics: Animals; Antioxidants; Benzimidazoles; Benzoxazoles; Biphenyl Compounds; Brain Edema; Brain Infarction; Cell Death; Cell Survival; Cells, Cultured; Cerebral Cortex; Chromans; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Fluorescent Dyes; Glutamic Acid; Hydrazines; Infarction, Middle Cerebral Artery; Inhibitory Concentration 50; Ischemia; Lipid Peroxidation; Male; Mice; Minocycline; Neurons; Neuroprotective Agents; Oxidative Stress; Picrates; Quinolinium Compounds; Saponins; Tetrazolium Salts; Time Factors