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

ABSTRACT: Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common ent-kaurane skeleton have been purified from Croton tonkinensis. METHODS:We examined any modifications of croton components (i.e., croton-01 [ent-18-acetoxy-7?-hydroxykaur-16-en-15-one], croton-02 [ent-7?,14?-dihydroxykaur-16-en-15-one] and croton-03 [ent-1?-acetoxy-7?,14?-dihydroxykaur-16-en-15-one] on either hyperpolarization-activated cation current (Ih) or erg-mediated K+ current identified in pituitary tumor (GH3) 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 Ih amplitude. Croton-03 (3 ?M) shifted the activation curve of Ih to a more negative potential by approximately 11 mV. The voltage-dependent hysteresis of Ih was also diminished by croton-03 administration. Croton-03-induced depression of Ih could not be attenuated by SQ-22536 (10 ?M), an inhibitor of adenylate cyclase, but indeed reversed by oxaliplatin (10 ?M). The Ih in INS-1 cells was also depressed effectively by croton-03. CONCLUSION:Our study highlights the evidence that these ent-kaurane diterpenoids might conceivably perturb these ionic currents through which they have high influence on the functional activities of endocrine or neuroendocrine cells.

SUBMITTER: Kuo PC 

PROVIDER: S-EPMC7072998 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature