thunberginol-b and hydrangenol

We examined the structure-activity relationships of isocoumarins, phthalides and stilbenes isolated from Hydrangeae Dulcis Folium and related compounds for the inhibition of histamine release in rat peritoneal mast cells. The activities of isocoumarins such as thunberginols A and B were more potent than those of dihydroisocoumarins such as hydrangenol and thunberginol G. The double bond at the 3-position seemed to be essential to potentiate the activity. The hydroxyl groups at the 8-, 3'- and 4'-positions of isocoumarin were essential for the activity, while the hydroxyl group at the 6-position was scarcely needed. Since the activities of benzylidenephthalides such as thunberginol F were more potent than those of hydramacrophyllols A and B, the presence of a double bond at the 3-position was needed to increase the activity. Moreover, the hydroxyl group at the 8-position was essential for the activity. On the time course study, thunberginols A, B and F completely inhibited histamine release by pretreatment at 100 microM for 1 to 15 min, whereas DSCG inhibited histamine release only following 1-min pretreatment at 1000 microM. These results suggested that the mechanisms of the inhibitory effect of thunberginols are different from that of DSCG.

Topics: Animals; Antigen-Antibody Reactions; Benzofurans; Benzopyrans; Bibenzyls; Calcimycin; Coumarins; Histamine Release; Immunoglobulin E; Inhibitory Concentration 50; Ionophores; Isocoumarins; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Peritoneum; Phenols; Phthalic Acids; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Stilbenes; Structure-Activity Relationship

Six new antiallergic and antimicrobial principles, thunberginols A, B, C, D, E, and F, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO. The chemical structures of thunberginols A, B, and F have been determined on the basis of chemical and physiocochemical evidence. Thunberginols A, B, and F showed more potent antiallergic activity than phyllodulcin, hydrangenol, and AA-861 in the in vitro test using the Schults-Dale reaction in sensitized guinea pig bronchial muscle. Thunberginols A, B, and F also exhibited antimicrobial activity against oral bacteria.

Topics: Animals; Anti-Bacterial Agents; Bacteroidaceae; Benzofurans; Benzopyrans; Benzoquinones; Bronchoconstriction; Coumarins; Guinea Pigs; In Vitro Techniques; Isocoumarins; Microbial Sensitivity Tests; Passive Cutaneous Anaphylaxis; Plant Extracts; Plants, Medicinal