One of the biological systems playing a major role in blood pressure regulation and in the pathology of the most important cardiovascular diseases is the renin-angiotensin system. It is well known that the deleterious effects of angiotensin II are mediated through the angiotensin II AT1 (AT1) receptor, which has been recognized as an effective target to develop antihypertensive drugs. Nevertheless, increasing interest is there to find drugs capable of activating protective and regenerative pathways like the activation of the angiotensin II AT2 (AT2) receptor (1).
A preliminary study of our group showed that extracts from the leaves from Cecropia obtusifolia Bertol., a plant used by Panamanian folk medicine as a remedy for hypertension, inhibited angiotensin II binding to the AT1 receptor in more than 50% (2). In this study, we have isolated the major compounds present in the butanol extract of the stems and leaves of this plant and evaluated their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used a cellular luminescence-based read-out system in which intracellular calcium signaling is measured in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Our results showed that the crude extract blocked the response in the AT1 receptor (9.4 ± 8.2%) and activated it in the AT2 receptor (91.8±2.5%). Interestingly, when the major compounds present in the active extract were tested individually they were less active (36.6±11.4 – 51.0±31.8% for AT1 and 0.00±0.00-45.0±24.9% for AT2) than the mixture suggesting a synergistic effect of these compounds. These results validate the traditional use of C. obtusifolia as an antihypertensive plant.
References
- Kaschina et al., Pharmacol Res 2017; 125(Pt A):39-47.
- Caballero-George et al., Phytomedicine 2001; 8(1):59-70