Methods
Chemicals and reagentsAll chemicals except those noted below were purchased from Abstract Background: Peperomia pellucida is used as a medicinal plant and as an antihypertensive remedy. We investigated the possible mechanism of this action and its impact on cytochrome P450 (CYP) enzyme activity.Methods: Mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized, normotensive Sprague-Dawley rats following intravenous administration of Peperomia pellucida aqueous (10-30 mg/ kg) plant extract (PPAE). Recordings of the contractile activity of the aortic rings to the extract (1.9-8.6 mg/ml) were done using standard organ bath techniques. Impact on CYP3A4 and CYP2D6 enzyme activities was investigated using human liver and heterologously expressed microsomes.
Results:We observed a dose-dependent reduction in systolic, diastolic, MAP and HR. Pre-treatment with atropine (2 mg/kg) and propranolol (1 mg/kg) but not mepyramine (2 mg/kg) significantly (p<0.05) reduced the hypotensive and negative chronotropic activities caused by the extract, while L-NAME (5 mg/kg) completely abolished it. PPAE significantly (p<0.05) relaxed the phenylephrine (10 -9 -10 -4 M) and KCl-induced contractions and displayed moderate inhibition of CYP3A4 enzyme activity with IC 50 values of 0.466 ± 0.126 mg/mL and 0.153 ± 0.054 mg/mL, respectively using heterogenously expressed CYP3A4 and human liver microsomes (HLMs) Conclusion: Results suggest dose-dependent hypotensive, bradycardic and vasorelaxant effects of PPAE are mediated through Nitric oxide-dependent mechanisms. The impact on CYPs enzyme activities indicate unlikely adverse drug effect when Peperomia pellucida is consumed with other medications reliant on CYP3A4 metabolism.
The chemical investigation of the organic extract of Canistrocarpus cervicornis, collected at Drunken Man’s Cay at Port Royal, Jamaica, has led to the isolation of two new dolastane diterpenes 4R-acetoxy-8S,9S-epoxy-14S-hydroxy-7-oxodolastane (1) and 4R-hydroxy-8S,9S-epoxy-14S-hydroxy-7-oxodolastane (2) and the previously isolated dolastane (4R,9S,14S)-4,9,14-trihydroxydolast-1(15),7-diene (3) as a major diterpene constituent. The structures of the new compounds were elucidated by extensive spectroscopic analyses. Compounds 1–3 were evaluated for their cytotoxicity against human tumor cell lines PC3 and HT29. The results revealed that the dolastane diterpenes (1–3) displayed moderate, concentration dependent, cytotoxicity.
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