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Inhibition of the L-type calcium channel by a standardised Olea europaea leaf extract: A phytochemical and electrophysiological examination
Cardiovascular diseases are still the leading causes of morbidity and mortality in industrialized countries with hypertension being one of the main risk factors . In Southern Europe Olea europaea leaves are known as a folk remedy for this ailment [2, 3]. The quality of the used leaf raw material and dry extract were analysed according to PhEur 5 monograph. In addition a gradient elution HPLC method was developed showing a fingerprint chromatogram with six characteristic phenolic compounds: oleuropein, hydroxytyrosol, tyrosol, verbascoside, apigenin-7-O-glucoside, and luteolin-7-O-glucoside . For pharmacological testing, we investigated the effects of a commercial Olea europaea leaf extract (OLE) on cultured cardiomyocytes and isolated rabbit hearts, which were perfused according to the Langendorff technique and connected to a 256 channel epicardial mapping system. Voltage clamp experiments were performed in cultured neonatal rat cardiomyocytes using a perforated-patch technique. OLE caused a concentration-dependent decrease in systolic left ventricular pressure and heart rate as well as an increase in relative coronary flow and a slight, but no significant prolongation of PQ-time. There were no significant changes between the groups in the activation-recovery-interval and its dispersion, total-activation-time, peak-to-peak amplitude, percentage of identical breakthrough-points and similar vectors of local activation. Voltage clamp experiments in cultured neonatal rat cardiomyocytes showed a significant decrease in maximum ICa,L by OLE which was reversible upon wash-out. Our findings demonstrate that OLE suppresses the L-type-calcium-channel directly and reversibly and thus help to understand the traditional use of OLE in the treatment of cardiovascular disease.
References: 1. Dhein, S. et al. (1993) Circulation 87: 617–630.
2. Rauwald, H. W. et al. (1991) Pharm Pharmacol Lett 1: 78–81.
3. Rauwald, H. W. et al. (1994) Phytother Res 8: 135–140.
4. Kampa, B. (2007) Diploma Thesis, Leipzig University