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The inhibition effect of uncarialin A on voltage-dependent L-type calcium channel subunit alpha-1C: Inhibition potential and molecular stimulation.
- Source :
-
International Journal of Biological Macromolecules . Sep2020, Vol. 159, p1022-1030. 9p. - Publication Year :
- 2020
-
Abstract
- Cardiovascular diseases, such as hypertension and cardiac failure, have become the most major and global cause for threatening human health in recent years. Uncaria rhynchophylla as a traditional Chinese medicine is widely used to treat hypertension for a long history, whereas its medicinal effective components and potential action mechanism are uncertain. Therefore, twenty-four alkaloids (1–24) isolated from U. rhynchophylla were assayed for their relaxant effects against phenylephrine (Phe)-induced contraction of rat mesenteric arteries. Among them, we surprisingly found that uncarialin A (21) exhibited most potent relaxation effect against Phe-induced contraction (IC 50 = 0.18 μM) in the manner of independent on endothelium-derived vasorelaxing factors and endothelium. All the experiments including measurement of Ca2+ in vascular smooth muscle cells (VSMCs) by fluorescence microscopy, whole-cell path clamp, molecular docking, and molecular dynamics, demonstrated that uncarialin A (21) could significantly inhibit L-type calcium channel subunit alpha-1C (Cav1.2) via the hydrogen bond interaction with amino acid residue Met1186, allowing the inhibition of Ca2+ inward current. Our results suggested that uncarialin A (21) could be served as a potential L-type Cav1.2 blocker in the effective treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01418130
- Volume :
- 159
- Database :
- Academic Search Index
- Journal :
- International Journal of Biological Macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 145117255
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2020.05.100