Possibilidades terapêuticas e risco toxicológico de Jatropha gossypiifolia L: uma revisão narrativa / Therapeutic possibilities and toxicological risk of Jatropha gossypiifolia L: a narrative review

A espécie Jatropha gossypiifolia L. (Euphorbiaceae), popularmente conhecida como pião-roxo, entre tantos outros nomes, é um bom exemplo do tênue limiar que separa o efeito terapêutico do tóxico. Apesar de ser classicamente conhecida como planta tóxica possui usos na medicina popular. Alguns desses efeitos têm sido comprovados em estudos experimentais, como os de antimicrobiano, antineoplásico, cicatrizante e hipotensor, sendo possivelmente explicados pela presença de substâncias como alcalóides, terpenóides, flavonóides, lignanas e taninos. Esta revisão aborda aspectos importantes, com ênfase na toxicidade crônica dessa espécie, de modo a servir de fonte de informação aos interessados em avaliar a relação risco/benefício do uso terapêutico de Jatropha gossypiifolia L.

The species Jatropha gossypiifolia L. (Euphorbiaceae), popularly known as bellyache bush, among several other names, is an important example of the tenuous threshold that separates the therapeutic from the toxic effect. Although traditionally known as a toxic plant, it has been used in folk medicine. Some of its effects have been proved by experimental studies as antimicrobial, antineoplastic, healing and hypotensive, likely explained by the presence of substances such as alkaloids, terpenoids, flavonoids, lignans and tannins. This review deals with important aspects, focusing on the chronic toxicity of this species, in order to serve as an information source for those interested in evaluating the risk-benefit ratio of the therapeutic use of Jatropha gossypiifolia L.

Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism.

Cecropia glaziovii Sneth is a common tree at the Southeastern Brazilian coast. As many other species of the genus, it shares the reputed folk use to treat heart failure, cough, asthma and bronchitis. The plant has been cultivated under controlled conditions and the 2% aqueous extract (AE) prepared with the dried leaves was standardized by its chemical contents on catechins, flavonoids and procyanidins. The present paper reports the antihypertensive activity of AE and of n-butanol fraction (BuF), an enriched semi-purified butanolic fraction used to isolate the main chemical constituents. Oral administration of AE and BuF induced hypotension in normotensive rats. The effect of AE (0.5 g/kg/bi, p.o.) was time and dose-dependent peaking at 2-3 weeks after daily administration. BuF was faster but not more active than AE. Both extracts decreased the hypertension of spontaneous hypertensive rats, the hypertension induced in rats by L-NAME treatment and that induced by constriction of one renal artery. The antihypertensive effect was maintained for as long as 60 days of treatment and was reversible upon drug washout at the same rate of its establishment. Acute i.v. administration of BuF to anesthetized rats induced a fast short-lasting hypotension and inhibited the pressor responses to noradrenaline, angiotensin I and angiotensin II by 40%. These results were indirect indications that the hypotension induced by AE is not related to ACE inhibition, increased NO synthesis, or specific blockade of alpha1 and AT1 receptors. It can be suggested that BuF interferes with the calcium handling mechanisms in smooth muscle cells and neurons. Intravenous injection of five out of nine compounds isolated from BuF produced immediate but short-lasting hypotension that does not correlate with the onset of the hypotension after oral treatment. This finding suggests that they may not be the compounds directly responsible for the delayed and sustained hypotension after per os administration of AE. The many compounds isolated from AE are under evaluation to determine its pharmacokinetics, mechanisms of action and interactions necessary to yield the plant effect. Although its mechanism is still unknown, AE seems to be an effective and safe antihypertensive phytomedicine.

Anti-inflammatory and anti-nociceptive activities of Pluchea quitoc (DC.) ethanolic extract.

Pluchea quitoc DC. (Asteraceae), a plant widely distributed throughout Brazil and popularly known as "quitoco", "madre-cravo" or "tabacarana", is used in traditional medicine for the treatment of inflammation, as well as of digestive and respiratory diseases. The anti-inflammatory and anti-nociceptive activities of the ethanolic extract (EE) from aerial parts of this plant were evaluated in mice and rats. Oral treatment with the EE (1-2g/kg, p.o.) decreased the paw oedema induced by carrageenan in rats, showed anti-nociceptive effects on the tail-flick test and on acid-induced writhing in mice, and inhibited both phases of pain (neurogenic and inflammatory) of the formalin test in rats. Topical application (EE 1.25, 2.5 and 5.0mg) inhibited the ear oedema induced by croton oil in mice. The results support the folkloric use of the plant in inflammatory processes.

Role of smooth muscle cell membrane potential in neointima formation in arteries of spontaneously hypertensive rats.

Based on observations that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) have altered resting potentials as well as abnormal cell proliferation rates, neointima formation after controlled balloon injury was compared in arteries from SHR and Wistar Kyoto rats (WKY). SHR aortic VSMC showed hyperpolarized resting membrane potentials (-93+/-8 mV) when compared to those from WKY (-61+/-6 mV). Histomorphometric analysis of cross sections from aortic segments submitted to balloon injury showed reduced neointima formation in SHR (neointima/media ratio: 0.04+/-0.03) as compared to WKY (0.2+/-0.1). On the other hand, in injured carotid arteries, neointima formation was more extensive in SHR (neointima/media ratio 5.0+/-0.9) than in WKY (0.8+/-0.7), leading in most cases to luminal occlusion. Measurements of VSMC resting potential showed that carotid artery cells from SHR were depolarized with respect to those from WKY (-46+/-4 vs. -69+/-5 mV, respectively). The results demonstrate an inverse relationship between VSMC membrane polarization and neointima formation in SHR arteries, suggesting that genetic modifications in SHR determine a dysfunctional cellular physiology that may influence cell proliferation subsequent to injury.

Abnormal proliferative response of the carotid artery of spontaneously hypertensive rats after angioplasty may be related to the depolarized state of its smooth muscle cells

Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 + or - 1.9 mV) compared to NWR (-69 + or - 1.4 mV), NWR 1K-1C (-60.8 + or - 1.6 mV), WKY (-67.1 + or - 3.2 mV) and WKY 1K-1C (-56.9 + or - 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 + or - 0.86) when compared to arteries of all the other groups (NWR 0.93 + or - 0.65, NWR 1K-1C 1.24 + or - 0.45, WKY 1.22 + or - 0.32, WKY 1K-1C 1.15 + or - 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state