Antiproliferative quillaic acid and gypsogenin saponins from Saponaria officinalis L. roots.

Nine quillaic acid and five gypsogenin bisdesmosides were isolated from roots of Saponaria officinalis L. (Caryophyllaceae). Seven of the quillaic acid saponins possessed a 3-O-ß-D-galactopyranosyl-(1 → 2)-[ß-D-xylopyranosyl-(1 → 3)]-ß-D-glucuronopyranosyl unit, but differed from each other in oligosaccharide units linked to the C-28 ester. The five gypsogenin saponins isolated from the roots all possessed the 3-O-ß-D-galactopyranosyl-(1 → 2)-[ß-D-xylopyranosyl-(1 → 3)]-ß-D-glucuronopyranosyl unit, with their oligosaccharide units linked to the C-28 ester differing. Structures were elucidated by extensive 1D and 2D NMR spectroscopy and mass spectrometry. The saponins were evaluated for growth inhibitory activity in two human cancer cell lines and hemolytic activity in sheep red blood cells.

Catharanthine dilates small mesenteric arteries and decreases heart rate and cardiac contractility by inhibition of voltage-operated calcium channels on vascular smooth muscle cells and cardiomyocytes.

Catharanthine is a constituent of anticancer vinca alkaloids. Its cardiovascular effects have not been investigated. This study compares the in vivo hemodynamic as well as in vitro effects of catharanthine on isolated blood vessels, vascular smooth muscle cells (VSMCs), and cardiomyocytes. Intravenous administration of catharanthine (0.5-20 mg/kg) to anesthetized rats induced rapid, dose-dependent decreases in blood pressure (BP), heart rate (HR), left ventricular blood pressure, cardiac contractility (dP/dt(max)), and the slope of the end-systolic pressure-volume relationship (ESPVR) curve. Catharanthine evoked concentration-dependent decreases (I(max) >98%) in endothelium-independent tonic responses of aortic rings to phenylephrine (PE) and KCl (IC(50) = 28 µM for PE and IC(50) = 34 µM for KCl) and of third-order branches of the small mesenteric artery (MA) (IC(50) = 3 µM for PE and IC(50) = 6 µM for KCl). Catharanthine also increased the inner vessel wall diameter (IC(50) = 10 µM) and reduced intracellular free Ca(2+) levels (IC(50) = 16 µM) in PE-constricted MAs. Patch-clamp studies demonstrated that catharanthine inhibited voltage-operated L-type Ca(2+) channel (VOCC) currents in cardiomyocytes and VSMCs (IC(50) = 220 µM and IC(50) = 8 µM, respectively) of MA. Catharanthine lowers BP, HR, left ventricular systolic blood pressure, and dP/dt(max) and ESPVR likely via inhibition of VOCCs in both VSMCs and cardiomyocytes. Since smaller vessels such as the third-order branches of MAs are more sensitive to VOCC blockade than conduit vessels (aorta), the primary site of action of catharanthine for lowering mean arterial pressure appears to be the resistance vasculature, whereas blockade of cardiac VOCCs may contribute to the reduction in HR and cardiac contractility seen with this agent.