calcimycin and baicalein

Mitogen-activated protein kinase (MAPK) is a family of serine/threonine kinase that appears to be a component common to signalling pathway initiated by a wide range of factors including hormones, differentiation factors and mitogens. Baicalein is a flavonoid derived from the root of Scutellaria baicaleins. From searching the inhibitors of prostaglandin synthesis in C6 rat glioma cells, we found that baicalein had a potent inhibitory activity of prostaglandin synthesis induced by either histamine or A23187, a Ca2+ ionophore. Baicalein inhibited histamine- and A23187-induced phosphorylation of MAPK in the cells, which was known to cause the phosphorylation of cytosolic phospholipase A2. Baicalein also inhibited the phosphorylation of MAPK kinase (MEK) induced by histamine or A23187 in the cells. In vitro kinase assay, baicalein inhibited the activities of raf but not MEK. These results imply that baicalein is a specific inhibitor of MAPK cascade, acting on phosphorylation of MEK by raf.

Topics: Animals; Calcimycin; Flavanones; Flavonoids; Free Radical Scavengers; Glioma; Histamine; Ionophores; Mitogen-Activated Protein Kinases; Phosphorylation; Prostaglandin Antagonists; Rats; Tumor Cells, Cultured

Inhibitory mechanism of the water extract of Scutellariae Radix on prostaglandin E2 (PGE2) release was examined in C6 rat glioma cells. Scutellariae Radix reduced a Ca2+ ionophore A23187-induced PGE2 release by inhibition of arachidonic acid (AA) liberation. Sho-saiko-to and San'o-shashin-to, which contain Scutellariae Radix, also inhibited PGE2 release. A23187 caused phosphorylation of mitrogen-activated protein kinase (MAPK), resulting in activation of cytosolic phospholipase A2 (cPLA2). Scutellariae Radix and baicalein inhibited the phosphorylation of MAPK. Baicalein, but not baicalin, inhibited A23187-induced PGE2 release. These results suggest that baicalein in Scutellariae Radix reduces AA liberation through the inhibition of the MAPK-cPLA2 pathway.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Arachidonic Acid; Calcimycin; Calcium-Calmodulin-Dependent Protein Kinases; Dinoprostone; Drugs, Chinese Herbal; Enzyme Inhibitors; Flavanones; Flavonoids; Glioma; Ionophores; Molecular Sequence Data; Phosphorylation; Prostaglandin Antagonists; Rats; Tumor Cells, Cultured

Studies were made on the effects of baicalein (5,6,7-trihydroxyflavone) on leukotrienes B4 and C4 biosyntheses and degranulation induced by calcium ionophore A23187 (A23187) in human polymorphonuclear leukocytes. Baicalein inhibited A23187-induced biosynthesis of leukotrienes B4 and C4 in human polymorphonuclear leukocytes. The concentration of baicalein required for 50% inhibition (IC50) of leukotrienes B4 and C4 formations was 1.46.10(-6) and 6.00.10(-7) M, respectively, using 1.0 microgram/ml of A23187. In addition, baicalein dose-dependently inhibited beta-glucuronidase and lysozyme releases induced by A23187, leukotriene B4 plus cytochalasin B and platelet-activating factor plus cytochalasin B. Furthermore, baicalein was found to inhibit dose-dependently Ca2+ uptake into the cells and Ca2+ mobilization from the intracellular stores.

Topics: Calcimycin; Calcium; Cyclic AMP; Cytochalasin B; Dose-Response Relationship, Drug; Flavanones; Flavonoids; Glucuronidase; Humans; Muramidase; Neutrophils; Platelet Activating Factor; SRS-A