benzofurans and Cerebrovascular-Disorders

Topics: Adult; Benzofurans; Carotid Artery Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Evaluation; Female; Furans; Humans; Lateral Medullary Syndrome; Male; Middle Aged; Succinates; Vasodilator Agents

Ischemic stroke (IS) is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. It has been a worldwide critical disease threatening to the health and life of human beings. Despite significant progresses achieved, effective treatment still remains a formidable challenge due to the complexity of the disease. Salvianolic acid B (Sal-B) and Puerarin (Pue) are two active neuroprotectants isolated from traditional Chinese herbs, Salvia miltiorrhiza and Kudzu root respectively, which have been used for the prevention and treatment of IS for thousands of years in China. The activities of two compounds against cerebral ischemia reperfusion injury have been confirmed via various pathways. However, the therapeutic efficacy of any of the two components is still unsatisfied. In the present study, the effect of the combination of Sal-B and Pue on IS was evaluated and validated in vitro and in vivo. The ratio of two compounds was firstly optimized based on the results of CoCl₂ damaged PC12 cells model. The co-administration exhibited significantly protective effect in CoCl₂ induced PC12 cells injury model by reducing ROS, inhibiting apoptosis and improving mitochondrial membrane potential in vitro. Moreover, Sal-B + Pue significantly relieved neurological deficit scores and infarct area than Sal-B or Pue alone in vivo. The results indicated that neuroprotection mechanism of Sal-B + Pue was related to TLR4/MyD88 and SIRT1 activation signaling pathway to achieve synergistic effect, due to the inhibition of NF-κB transcriptional activity and expression of pro-inflammatory cytokine (TNF-α, IL-1β, IL-6). In conclusion, the combination of Sal-B and Pue exerted much stronger neuroprotective effect than Sal-B or Pue alone, which provides a potential new drug and has great significance for the treatment of IS.

Topics: Animals; Apoptosis; Benzofurans; Brain Ischemia; Cerebrovascular Disorders; Cobalt; Drug Combinations; Drug Synergism; Gene Expression Regulation; Interleukin-1beta; Interleukin-6; Isoflavones; Middle Cerebral Artery; Myeloid Differentiation Factor 88; Neuroprotective Agents; NF-kappa B; PC12 Cells; Rats; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Effects of NBP on liability of stroke, life span and neurological deficits following stroke were studied in stroke prone spontaneously hypertensive rats (SHRsp). The SHRsp rat was kept on 1% NaCl solution as drinking water and was fed 15 g soft food containing 0.6-0.8 g NaCl per day. Total NaCl intake for one rat was 1.1-1.3 g per day. After the onset of stroke, tap water and normal food was given instead of that containing NaCl. The neurological deficits were evaluated by a specially designed scoring system. These symptoms were divided into 4 degrees (1-4). Grade 1. stress (mild). Grade 2. forelimb or head twitch or with stress (severe). Grade 3. hemiparalysis, body inclined or disabled. Grade 4. paralysis, tremor or convulsion. Blood pressure, heart rate and body weight were measured once every 2 weeks. The weights of heart, brain and kidneys were also measured. The results show that NBP pre-treatment at the dose of 100 mg.kg-1.d-1 po delayed the onset of stroke. So, like nimodipine, NBP showed a stroke preventive action in SHRsp rats. In addition, treatment with NBP 100 mg.kg-1.d-1 po after the onset of stroke, the life span was prolonged and the score of neurological deficit decreased significantly. Because high blood pressure can not be lowered by NBP treatment, therefore, the protective effect against stroke can not be explained by the effect of hypotension. No change was found in BP, HR and the organ weight. The results indicate that NBP is expected to be useful in the treatment of stroke.

Topics: Animals; Benzofurans; Blood Pressure; Body Weight; Cerebrovascular Disorders; Heart Rate; Male; Neuroprotective Agents; Nimodipine; Rats; Rats, Inbred SHR; Stereoisomerism

A series of alpha-tocopherol analogues was synthesized with potential therapeutic value for such pathological conditions as stroke and trauma. A set of criteria such as the inhibition of in vitro lipid peroxidation, superoxyl radical scavenging, and brain penetration, as measured by ex vivo inhibition of lipid peroxidation, was applied to select the most effective compound. 2,3-Dihydro-2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)methyl]-1 - benzofuran-5-ol dihydrochloride (22) was selected because of its superior antioxidant properties and better brain penetration. This compound also protected mice against the effects of head injury. The criteria thus turned out to be useful for the characterization of a neuroprotective analogue of alpha-tocopherol.

Topics: Animals; Benzofurans; Brain; Cerebrovascular Disorders; Craniocerebral Trauma; Drug Evaluation, Preclinical; Free Radical Scavengers; Lipid Peroxidation; Male; Mice; Superoxides; Vitamin E

Topics: Aged; Benzofurans; Cerebrovascular Circulation; Cerebrovascular Disorders; Female; Humans; Lactones; Male; Middle Aged; Psychological Tests; Vasodilator Agents