6-ketoprostaglandin-f1-alpha and 3-n-butylphthalide

The effects of dl-3-n-butylphthalide (dl-NBP), l-3-n-butylphthalide (l-NBP), and d-3-n-butylphthalide (d-NBP) on the production of nitric oxide (NO), epoprostenol (Epo) and endothelin-1 (ET-1) were investigated in cerebrovascular and aortic endothelium in culture.. Bovine cerebral endothelial cells (BCEC) and bovine aortic endothelial cells (BAEC) were cultured in Medium 199 in vitro. After incubation with dl-, l-, and d-NBP for 24 h, the release of NO, Epo, and ET-1 were analyzed by using spectrometry assay and radioimmunoassay (RIA) respectively.. Low concentrations of dl- and l-NBP (0.1-10 mumol.L-1) enhanced nitrite and 6-ketoprostaglandin F1 alpha (6-ketoPGF1 alpha) production in both BAEC and BCEC after a 24-h incubation, and l-NBP has a potent effect on promoting Epo production in BCEC. The production of ET-1 secreted by BCEC and BAEC was increased after TNF alpha stimulation, this enhancement was not blunted by the simultaneous addition of dl-, l-, and d-NBP.. 1) dl-NBP and l-NBP increase NO production in both BCEC and BAEC. 2) l-NBP increases more Epo production in BCEC than that in BAEC, and dl-NBP has selective effect on increasing Epo production in BCEC.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Aorta; Benzofurans; Cattle; Cells, Cultured; Cerebral Cortex; Endothelin-1; Endothelium, Vascular; Epoprostenol; Neuroprotective Agents; Nitric Oxide; Stereoisomerism

The effects of 3-n-butylphthalide(NBP) on the levels of 6-keto-PGF1 alpha, TXB2 and 6-keto-PGF1 alpha/TXB2 ratio were studied with methods of RIA. d-NBP and l-NBP(0.1-100 mumol.L-1) concentration-dependently increased 6-keto-PGF1 alpha release, decreased TXB2 release from neuronal cells, and significantly enhanced extracellular 6-keto-PGF1 alpha/TXB2 ratio in primary cultured rat cortical neurons exposed to hypoxic-hypoglycemic media for 5 h or hypoxic-hypoglycemic media for 5 h following normal media for 3 h. Aspirin(0.1-100 mumol.L-1) was also shown to inhibit TXB2 release from cortical neurons in a dose-dependent manner. However aspirin only increased 6-keto-PGF1 alpha/TXB2 ratio at low dose because aspirin inhibited both 6-keto-PGF1 alpha and TXB2 release simultaneously at large dose(10-100 mumol.L-1). This suggests that the action of l-NBP, d-NBP and dl-NBP on the increase of 6-keto-PGF1 alpha/TXB2 ratio might be one of the mechanisms in which NBP enhanced focal cerebral blood flow and improved ischemic brain damage.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Benzofurans; Cell Hypoxia; Cells, Cultured; Cerebral Cortex; Drugs, Chinese Herbal; Female; Fetus; Glucose; Neurons; Neuroprotective Agents; Rats; Rats, Wistar; Thromboxane B2

To study the effects of dl-3-n-butylphthalide (NBP) on the changes of thromboxane B2 (TXB2) and 6-keto-PGF1 alpha (6-keto-PGF1 alpha) contents in hippocampus, striatum, and cerebral cortex of rats subjected to focal cerebral ischemia followed by reperfusion.. Focal cerebral ischemia was induced by inserting a nylon suture into intracranial segment of internal carotid artery from external carotid artery and blockade of the origin of middle cerebral artery. For reperfusion, the suture was pulled out to restore the blood flow to the ischemic brain. Determination of TXB2 and 6-keto-PGF1 alpha was performed by RIA method.. Reperfusion following focal cerebral ischemia resulted in increases in TXB2 at 5 min and 6-keto-PGF1 alpha at 30 min and a decrease in the ratio of epoprostenol (PGI2)/thromboxane A2 (TXA2) (6-keto-PGF1 alpha/TXB2) at 5 min in hippocampus, striatum, and cerebral cortex. NBP 10 mg.kg-1 reduced the content of TXB2 without decreasing effect on 6-keto-PGF1 alpha. NBP 20 mg.kg-1 reduced both TXB2 and 6-keto-PGF1 alpha in lesser extent than aspirin (Asp, 20 mg.kg-1). NBP 20 or 10 mg.kg-1 elevated the ratio of PGI2/TXA2 after reperfusion, but Asp 20 mg.kg-1 did not increase the ratio except in striatum at 5 min after reperfusion.. NBP increases the ratio of PGI2/TXA2 which may have beneficial effects on the impaired microcirculation in postischemic brain tissues.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Benzofurans; Brain; Ischemic Attack, Transient; Neuroprotective Agents; Rats; Reperfusion Injury; Thromboxane B2