[Show abstract][Hide abstract] ABSTRACT: Panama is a unique terrestrial bridge of extreme biological importance. It is one of the "hot spots" and occupies the fourth place among the 25 most plant-rich countries in the world, with 13.4 % endemic species. Panamanian plants have been screened for a wide range of biological activities: as cytotoxic, brine shrimp-toxic, antiplasmodial, antimicrobial, antiviral, antioxidant, immunosuppressive, and antihypertensive agents. This review concentrates on ethnopharmacological uses of medicinal plants employed by three Amerindian groups of Panama and on selected plants with novel structures and/or interesting bioactive compounds. During the last quarter century, a total of approximately 390 compounds from 86 plants have been isolated, of which 160 are new to the literature. Most of the work reported here has been the result of many international collaborative efforts with scientists worldwide. From the results presented, it is immediately obvious that the Panamanian flora is still an untapped source of new bioactive compounds.
[Show abstract][Hide abstract] ABSTRACT: I t is widely recognized that developing countries in the tropics that harbor a large fraction of the world's bio-diversity could, in principle, obtain substantial benefits from their biodiversity. The challenge has been to harness the eco-nomic value of sustainable uses of biodiversity in order to jus-tify the conservation of habitat in its natural state. Promising strategies for meeting this challenge include ecotourism, car-bon credits obtained from intact forest, and ecosystem ser-vices, such as the provision of clean water. Here we focus on how bioprospecting, the investigation of biodiversity as a source of useful medicines or genes (ten Kate and Laird 1999), might, in practice, provide the expected benefits. The Convention on Biological Diversity (1992–1993) and more recent agreements recognize that nations have owner-ship of, and can control access to, species ("genetic resources") within their boundaries; these agreements mandate equi-table sharing of the benefits derived from biodiversity (Gollin 1993, 1999). A principal focus has been on the legal issues con-cerning bioprospecting, such as the definition of prior in-formed consent for the use of traditional knowledge and specification of benefit-sharing arrangements (Blaustein 2006, CBD 2006). This emphasis resulted from the many cases—some recent—of the use of biodiversity without rec-ompense, as occurred with the insecticide from the Indian tree Azadirachta indica (neem), which has low toxicity to verte-brates, and with a heat-stable enzyme from the bacterium Thermus aquaticus, which is a key research tool. As a con-sequence, many governments have inhibited basic research on biodiversity (Grajal 1999, Gómez-Pompa 2004). It is very likely that biodiversity-based research carried out by phar-maceutical and agricultural companies also has been inhib-ited, although the extent of this inhibition is difficult to quantify. Even though bioprospecting research could promote substantial economic growth in areas with high biological diversity, such as the tropics, countries there have failed to capture the value of their biodiversity.
[Show abstract][Hide abstract] ABSTRACT: Bioprospecting has frequently been cited as a sustainable use of biodiversity. Nevertheless, the level of bioprospecting in biodiversity-rich tropical regions falls below its potential, with the result that bioprospecting has produced only limited economic benefits. We present a bioprospecting program that, in addition to promoting drug discovery, provides economic benefits to and promotes conservation in Panama through the sustainable use of biodiversity. The program was initiated using insights from 20 years of nonapplied ecological research to enhance the likelihood of finding treatments for human disease. Samples are not sent abroad; rather, most of the research is carried out in Panamanian laboratories. Panama has received immediate benefits for the use of its biodiversity in the form of research funding derived from sources outside Panama, training for young Panamanian scientists, and enhanced laboratory infrastructure. Over the long term, discoveries derived from bioprospecting may help to establish research-based industries in Panama.
[Show abstract][Hide abstract] ABSTRACT: Different types of triterpenes including saponins and aglycons were evaluated for their ability to inhibit [3H] BQ-123 and [3H] angiotensin II binding to the human endothelin 1 ETA and angiotensin II AT1 receptors, respectively. Selectivity for only one of the two receptors was exhibited by asiatic acid and its saponins (ETA) and oleanolic acid (AT1). To a lesser extent betulinic acid, beta-amyrin and friedelin also showed selectivity for the ETA receptor. To address the question whether the effect of saponins on cell membranes might interfere with the normal binding of specific radioligands to their receptors, the activity of saponins with different haemolytic properties were compared. Highly haemolytic saponins such as alpha-hederin and beta-escine showed partial (60%) inhibition of radioligand-binding to the ETA receptor and complete inhibition (100%) to the AT1 receptor. Moreover, the haemolytically inactive kryptoescine, at the same concentration, caused complete inhibiton of radioligand-binding to both receptors, indicating that inhibition of receptor binding was not related to the membrane-interacting properties of saponins.
Phytotherapy Research 10/2004; 18(9):729-36. · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The type of interaction of 5-methyl-2,3,7,8-bis(methylenedioxy)benzo[c]phenanthridinium (sanguinarine), an alkaloid isolated from the root of Bocconia frutescens L., with the human angiotensin AT(1) receptor was evaluated in both intact cells and membrane binding of [3H](2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid) ([3H]candesartan). The results indicate that the inhibition of [3H]candesartan binding by sanguinarine is independent of cell viability, since the alkaloid inhibited at a similar extent radioligand binding on both intact Chinese hamster ovary (CHO) cells transfected with the human angiotensin AT(1) receptor (hAT(1)) and their cell membranes (K(i)=0.14 and 1.10 microM, respectively). The unsuccessful recovery of [3H]candesartan binding after washing sanguinarine off the cells suggested a nearly irreversible or slow reversible interaction. Saturation binding studies showed a substantial reduction of the B(max) without affecting the K(d). In addition, the presence of 2-n-butyl-4chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole (losartan) could not prevent sanguinarine inhibition of [3H]candesartan binding neither. The present findings indicate that sanguinarine interacts with the receptor in a slow, nearly irreversible and noncompetitive manner.
European Journal of Pharmacology 02/2003; 458(3):257-62. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A bioassay-guided fractionation of the 70% acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT 1 receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [3H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins.
[Show abstract][Hide abstract] ABSTRACT: A bioassay-guided fractionation of the 70% acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT 1 receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [3H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins
[Show abstract][Hide abstract] ABSTRACT: A bioassay-guided fractionation of the 80 % ethanolic extract from Bocconia frutescens L. roots, showing a dose-dependent inhibitory effect towards both [(3)H]-angiotensin II and [(3)H]-BQ-123 binding to the human angiotensin II AT 1 and endothelin 1 ET(A) receptors, led to an alkaloidal subfraction as the only responsible fraction for the activity of the whole extract. Among the alkaloids present in this fraction sanguinarine and chelerythrine were significant inhibitors of [(3)H]-angiotensin II binding (hAT 1 receptor), with IC(50) values within the micromolar range. On the contrary, the [(3)H]-BQ-123 binding (ET(A) receptor) was only weakly inhibited. Moreover, other members of the isoquinoline alkaloid family such as chelidonine and some protoberberine alkaloids exhibited no affinity for the two receptors. The present work shows the possible structure-activity relationship for these benzophenanthridine alkaloids on a screening bioassay using both stably transfected Chinese hamster ovary (CHO) and the human neuroblastoma SK-N-MC cells. Furthermore, the ability of these compounds to block AT(1) and/or ET(A) receptors may provide some justification for the traditional use of Bocconia frutescens L. to control hypertension.
[Show abstract][Hide abstract] ABSTRACT: Nineteen plants from the Republic of Panama were selected by their traditional uses in the treatment of hypertension, cardiovascular, mental and feeding disorders and 149 extracts were screened using radioligand-receptor-binding assays. The methanol:dicloromethane extracts of the bark and leaves of Anacardium occidentale L., the leaves of Begonia urophylla Hook., the roots of Bocconia frutescens L., the stems and leaves of Cecropia cf.obtusifolia Bertol., the branches of Clusia coclensis Standl., the bark of Cochlospermum vitifolium (Willd.)Spreng., the roots of Dimerocostus strobilaceus Kuntze, the bark of Guazuma ulmifolia Lam., the leaves of Persea americana Mill. and the branches of Witheringia solanaceae L'Her. inhibited the [3H]-AT II binding (angiotensin II AT1 receptor) more than 50%. Only extracts of the roots of Dimerocostus strobilaceus Kuntze and the stems of Psychotria elata (Sw.) Hammel were potent inhibitors of the [3H] NPY binding (neuropeptide Y Y1 receptor) more than 50% and the ethanolic extracts of the leaves of Cecropia cf. obtusifolia Bertol., the leaves of Hedyosmum bonplandianum H.B.K., the roots of Bocconia frutescens L., the stem of Cecropia cf. obtusifolia Bertol. and the branches of Psychotria elata (Sw.) Hammel showed high inhibition of the [3H] BQ-123 binding (endothelin-1 ET(A) receptor) in a preliminary screening. These results promote the further investigation of these plants using the same assays.
[Show abstract][Hide abstract] ABSTRACT: The limited international resources for economic aid and conservation can only mitigate poverty and losses of biodiversity.
Hence, developing nations must establish the capacity to resolve their problems. Additionally, policy-makers and donors need
to obtain scientific input on issues such as global change and ecosystem services. We propose that for nations rich in biodiversity,
ecosystem services derived from bioprospecting, or drug discovery, could contribute to economic development. In the case where
unstudied samples are shipped abroad for research, the chances of obtaining royalties are infinitesimally small. Therefore
developing nations will only realize benefits from bioprospecting through in-country research on their own biodiversity. Policy-makers
and donors have failed to appreciate the value of this approach. In order to provide an example of the inherent links between
conservation and sustainable economic development, we initiated a drug discovery effort in Panama that emphasizes local benefit.
As much of the drug discovery process as possible is conducted in Panamanian laboratories, providing jobs dependent on intact
biodiversity and enhancing local research and training. In short, research, plus the spin-offs from research, provide immediate
and long-lasting benefits to Panama. The connection between conservation and development has been highlighted in publicity
about the project in Panama’s urban media. This provides a constructive alternative to the perception the among the urban
populace that economic development inevitably competes with conservation. In summary, our program uses biodiversity to promote
human health as well as to support research capacity, economic development and conservation within Panama. The program provides
an example of the widely recognized but little developed concept of bioprospecting research as an ecosystem service.
KeywordsBioprospecting-Chagas’ disease-Convention on biological diversity-Ecosystem services-ICBG-Leishmaniasis-Malaria-Panama-Policy-makers-Sustainable development
Biodiversity and Conservation 16(10):2789-2800. · 2.26 Impact Factor