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-7α-hydroxykaur-16-en-15-one], croton-02 [ent-7α,14β-dihydroxykaur-16-en-15-one] and croton-03 [ent-1β-acetoxy-7α,14β-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 μM) 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 μM), an inhibitor of adenylate cyclase, but indeed reversed by oxaliplatin (10 μM). 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.

• Authors: Ping-Chung Kuo, Yen-Chin Liu, Yi-Ching Lo, Sheng-Nan Wu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 4 (Feb 13 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32070065 (Publication Type: Journal Article)

Chemical References

• Diterpenes, Kaurane
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
• Plant Extracts
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (genetics)
• Animals
• Cell Line, Tumor
• Croton (chemistry)
• Disease Models, Animal
• Diterpenes, Kaurane (chemistry, pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (antagonists & inhibitors, chemistry, genetics)
• Molecular Structure
• Pituitary Neoplasms (drug therapy, genetics, pathology)
• Plant Extracts (chemistry, pharmacology)
• Plant Leaves (chemistry)
• Rats