Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of ent-Kaurane-Type Diterpenoids from Croton tonkinensis

摘要

Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common -kaurane skeleton have been purified from . Methods: We examined any modifications of croton components (i.e., croton-01 [ -18-acetoxy-7α-hydroxykaur-16-en-15-one], croton-02 [ -7α,14β-dihydroxykaur-16-en-15-one] and croton-03 [ -1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one] on either hyperpolarization-activated cation current ( ) or -mediated K current identified in pituitary tumor (GH ) cells and in rat insulin-secreting (INS-1) cells via patch-clamp methods. Results: Addition of croton-01, croton-02, or croton-03 effectively and differentially depressed amplitude. Croton-03 (3 μM) shifted the activation curve of to a more negative potential by approximately 11 mV. The voltage-dependent hysteresis of was also diminished by croton-03 administration. Croton-03-induced depression of could not be attenuated by SQ-22536 (10 μM), an inhibitor of adenylate cyclase, but indeed reversed by oxaliplatin (10 μM). The in INS-1 cells was also depressed effectively by croton-03. Conclusion: Our study highlights the evidence that these -kaurane diterpenoids might conceivably perturb these ionic currents through which they have high influence on the functional activities of endocrine or neuroendocrine cells.