ABSTRACT
Title
Discovery of novel vascular active agents from selected Vietnamese medicinal plants.
Authors
M. Durante.
Doctorate School in Pharmacology and Toxicology
Dept. of Neuroscience, University of Siena. Italy
Doctorate School in Pharmacology and Toxicology
Dept. of Neuroscience, University of Siena. Italy
Abstract
The vasorelaxing effect of 29 samples (18 plant extracts, 2 pure compounds, and 9 fractions) isolated from Vietnamese medicinal plants has been assessed using rat vascular preparations. VIP-6, VIP-10, VIP-11, and VIP-14 (one fraction and 3 extracts from plants belonging to the Rutaceae family), and VIP-23 (osthole, isolated from the fruit of Cnidium onnieri belonging to the Umbeliferae family) inhibited rat aorta rings tonic contraction induced by 60 mM K+ in a concentration-dependent manner. VIP-23, the most potent compound, showed an IC50 value of 7 µM. An in-depth analysis of the effects of VIP-23 on rat tail artery myocytes was performed by means of whole-cell patch-clamp recordings of Cav1.2 Ca2+ current [ICa1.2]. At a holding potential of -50 mV, VIP-23 decreased ICa1.2 in a concentration-dependent manner with an IC50 value of 10 µM. The maximum and the threshold of the ICa1.2-voltage relationship remained unaffected. VIP-23 (10 µM) modified the inactivation kinetics of ICa1.2 and shifted, in a concentration-dependent manner, the voltage dependence of the inactivation curve to more negative potentials. In conclusion, VIP-23 (osthole) is a naturally-occurring vasodilator that, by inhibiting ICa1.2, may represent a scaffold for the design of novel drugs of potential interest for treatment of systemic hypertension.
Acknowledgements: This work was funded by a grant from Ministero degli Affari Esteri (Rome, Italy) as stipulated by Law 212 (26-2-1992) to a joint research projects entitled “Discovery of novel cardiovascular active agents from selected Vietnamese medicinal plants”within the IV executive programme of scientific and technological co-operation between Italy and Vietnam for the years 2009-2011.
Acknowledgements: This work was funded by a grant from Ministero degli Affari Esteri (Rome, Italy) as stipulated by Law 212 (26-2-1992) to a joint research projects entitled “Discovery of novel cardiovascular active agents from selected Vietnamese medicinal plants”within the IV executive programme of scientific and technological co-operation between Italy and Vietnam for the years 2009-2011.