Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells.

BACKGROUND/AIM: Aurelianolide A and B were identified and isolated from Aureliana fasciculata var. fasciculata leaves. Withanolides are naturally occurring C-28 steroidal lactone triterpenoids with cytotoxic and anticancer properties, among other relevant pharmacological activities. Herein we have described, for the first time, the cytotoxic effects of aurelianolides on human cancer cells. MATERIALS AND METHODS: Aurelianolide A and B were tested on human leukemia cell lines: THP-1, MOLT-4, Jurkat, K562 and K562-Lucena 1. RESULTS: For aurelianolide A, MOLT-4 had the lower IC50 (1.17 µM) and for aurelianolide B, Jurkat was the most susceptible cell line (IC50 2.25 µM). On the other hand, the multidrug resistant (MDR) cell line K562-Lucena 1 showed higher IC50 for both aurelianolides. Using 293T, a non-tumor embryonic kidney cell line, we observed an excellent selectivity index for both aurelianolides, from 2.24 (aurelianolide B in K562-Lucena 1) to 45.5 (aurelianolide A in MOLT-4). Aurelianolide A and B activated caspase 3/7 with consequent induction of apoptosis on Jurkat and K562-Lucena 1 cell lines. We have not observed induction of necrosis. CONCLUSION: Aurelianolides A and B have important cytotoxic effects on human leukemia cell lines by the activation of the caspase pathway.

Utilization of the Plant Clusia Fluminensis Planch & Triana Against Some Toxic Activities of the Venom of Bothrops jararaca and B. jararacussu Snake Venom Toxic Activities.

BACKGROUND: In Brazil, the Bothrops genus accounts for 87% of registered snakebites, which are characterized by hemorrhage, tissue necrosis, hemostatic disturbances, and death. The treatment recommended by governments is the administration of specific antivenoms. Although antivenom efficiently prevents venom-induced lethality, it has limited efficacy in terms of preventing local tissue damage. Thus, researchers are seeking alternative therapies able to inhibit the main toxic effects of venoms, without compromising safety. OBJECTIVE: The study aimed to test the ability of aqueous extracts of leaves, stems, and fruits of the plant Clusia fluminensis to neutralize some toxic effects induced by the venoms of Bothrops jararaca and Bothrops jararacussu. METHODS: The plant extracts were incubated with venoms for 30 min. at 25 °C, and then in vitro (coagulant and proteolytic) and in vivo (hemorrhagic, myotoxic, and edematogenic) activities were evaluated. In addition, the extracts were administered to animals (by oral, intravenous or subcutaneous routes) before or after the injection of venom samples, and then hemorrhage and edema assays were performed. In addition, a gel solution of the fruit extract was produced and tested in terms of reducing hemorrhage effects. A chemical prospection was performed to identify the main classes of compounds present in the extracts. RESULTS: All the extracts inhibited the activities of the two venoms, regardless of the experimental protocol or route of administration of the extracts. Moreover, the gel of the fruit extract inhibited the venom-induced-hemorrhage. The extracts comprised of tannins, flavonoids, saponins, steroids, and terpenoids. CONCLUSION: Antivenom properties of C. fluminensis extracts deserve further investigation in order to gain detailed knowledge regarding the neutralization profile of these extracts.

Leishmanicidal Activity of Withanolides from Aureliana Fasciculata var. Fasciculata.

Leishmaniasis is the generic denomination to the neglected diseases caused by more than 20 species of protozoa belonging to the genus Leishmania. The toxic and parenteral-delivered pentavalent antimonials remain to be the first-line treatment. However, all the current used drugs have restrictions. The species Aureliana fasciculata (Vell.) Sendtner var. fasciculata is a native Brazilian species parsimoniously studied on a chemical point of view. In this study, the antileishmanial activity of A. fasciculata was evaluated. Among the evaluated samples of the leaves, the dichloromethane partition (AFfDi) showed the more pronounced activity, with IC50 1.85 µg/ml against promastigotes of L. amazonensis. From AFfDi, two active withanolides were isolated, the Aurelianolides A and B, with IC50 7.61 µM and 7.94 µM, respectively. The withanolides also proved to be active against the clinically important form, the intracellular amastigote, with IC50 2.25 µM and 6.43 µM for Aurelianolides A and B, respectively. Furthermore, withanolides showed results for in silico parameters of absorption, distribution, metabolism, excretion, and toxicity (ADMET) similar to miltefosine, the reference drug, and were predicted as good oral drugs, with the advantage of not being hepatotoxic. These results suggest that these compounds can be useful as scaffolds for planning drug design.

Isolation of a larvicidal compound from Piper solmsianum C.DC. (Piperaceae).

The Aedes aegypti mosquito is one of the major vectors of arboviruses. These diseases have re-emerged and the insecticides used nowadays are toxic to mammals and environment and have only been effective in the short-term. In this context, natural products are an alternative. The genus Piper has many active compounds against arthropods, including neolignans. The present study evaluated the larvicidal potential of the n-hexanic extract of Piper solmsianum and eupomatenoid-6, identified by GC-MS and NMR techniques, from this extract against Ae. aegypti. The crude extract (100 µg/mL) killed 80% and 98.3% of larvae in the first and third day, respectively. Eupomatenoid-6 exhibited LD50 of 19.33 µM and LD90 of 28.68 µM and was then assayed in human fibroblast cells (MRC5), showing an IC50 of 39.30 µM with estimated LD50 of 42.26 mmol/kg. Our results indicate eupomatenoid-6 as a potent insecticide with relatively low toxicity for mammals.

Antiviral and Immunomodulatory Effects of Norantea brasiliensis Choisy on Dengue Virus-2.

BACKGROUND/AIMS: Severe dengue fever is a result of exacerbated immune responses and no specific treatments are available. We evaluated the antiviral and immunomodulatory effects of Norantea brasiliensis Choisy. METHODS: Human adherent monocytes infected in vitro with dengue virus (DENV)-2 were incubated with the crude ethanol extract from leaves (NB1) or 3 derived fractions: dichloromethane (NB3), ethyl acetate (NB5), and butanolic (NB6) partitions. The antiviral and immunomodulatory activities were determined by intracellular detection of DENV antigen within monocytes and by secreted NS1 viral protein and cytokines. RESULTS: The crude extract alone exhibited both antiviral activities (intracellular and secreted antigens) and all fractions derived from this extract modulated NS1 production. Regarding the immunomodulatory effect, among the secreted factors, TNF-α was inhibited by NB3 and NB6; IL-6 was inhibited by NB1, NB3, and NB6; IL-10 by NB1 and NB3; and IFN-α by NB6. The crude extract (NB1) presented the best antiviral effect, whereas the dichloromethane fraction (NB3) presented an immunomodulatory effect in the inflammatory and anti-inflammatory cytokines. CONCLUSION: During in vitro DENV infection, N. brasiliensis Choisy exerts both antiviral and immunomodulatory effects that are likely associated, considering that less viral load may lead to less immunostimulation.

Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolius is a species of plant from the Anacardiaceae family, which can be found in different regions of Brazil. Schinus is popularly known as aroeirinha, aroeira-vermelha, or Brazilian pepper. In folk medicine, S. terebinthifolius is used for several disorders, including inflammatory conditions, skin wounds, mucosal membrane ulcers, respiratory problems, gout, tumors, diarrhea and arthritis. According to chemical analyses, gallic acid, methyl gallate and pentagalloylglucose are the main components of hydroalcoholic extracts from S. terebinthifolius leaves. In the present study, we demonstrated the ability of a hydroalcoholic extract to inhibit cell migration in arthritis and investigated the mechanisms underlying this phenomenon. MATERIALS AND METHODS: The anti-inflammatory effect of S. terebinthifolius hydroalcoholic leaf extract (ST-70) was investigated in a zymosan-induced experimental model of inflammation. Male Swiss and C57Bl/6 mice received zymosan (100 µg/cavity) via intra-thoracic (i.t.) or intra-articular (i.a.) injection after oral pre-treatment with ST-70. The direct action of ST-70 on neutrophils was evaluated via chemotaxis. RESULTS: ST-70 exhibited a dose-dependent effect in the pleurisy model. The median effective dose (ED50) was 100mg/kg, which inhibited 70% of neutrophil accumulation when compared with the control group. ST-70 reduced joint diameter and neutrophil influx for synovial tissues at 6h and 24h in zymosan-induced arthritis. Additionally, ST-70 inhibited synovial interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (CXCL1/KC) and Tumor Necrosis Factor (TNF)-α production at 6h and CXCL1/KC and IL-1ß production at 24h. The direct activity of ST-70 on neutrophils was observed via the impairment of CXCL1/KC-induced chemotaxis in neutrophils. Oral administration of ST-70 did not induce gastric damage. Daily administration for twenty days did not kill any animals. In contrast, similar administrations of diclofenac induced gastric damage and killed all animals by the fifth day. CONCLUSIONS: Our results demonstrated significant anti-inflammatory effects of ST-70, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, such as joint inflammation.

3ß-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through modulation of intracellular levels of GSH and inhibition of GST activity.

ABC transporter overexpression is an important mechanism of multidrug resistance (MDR) and one of the main obstacles to successful cancer treatment. As these proteins actively remove chemotherapeutics from the tumor cells, the pharmacological inhibition of their activity is a possible strategy to revert drug resistance. Moreover, the ability of MDR inhibitors to sensitize resistant cells to conventional drugs is important for their clinical use. Evidence has shown that the multidrug resistance protein 1 (MRP1/ABCC1) is a negative prognostic marker in patients with lung, gastric, or breast cancers or neuroblastoma. Previous data have shown that 3ß-acetyl tormentic acid (3ATA) inhibits the transport activity of the protein MRP1/ABCC1. In this study, we evaluated the ability of 3ATA to sensitize an MDR cell line (GLC4/ADR), which overexpresses MRP1, and investigated the anti-MRP1 mechanisms activated by 3ATA. The results showed that 3ATA is able to reverse the resistance of the MDR cell line to doxorubicin and vincristine, two drugs that are commonly used in cancer chemotherapy. Regarding the sensitizing mechanism induced by 3ATA, this work shows that the triterpene does not modulate the expression of MRP1/ABCC1 but is able to reduce total intracellular glutathione (GSH) levels and decrease the activity of glutathione-s-transferase (GST), the enzyme responsible for the glutathione conjugation of xenobiotics. Together, these results show that 3ATA sensitizes the MDR cell line overexpressing MRP1/ABCC1 to antineoplastic drugs and that this effect is mediated by the modulation of intracellular levels of GSH and GST activity.

Chemical composition and efficacy in the egg-hatching inhibition of essential oil of Piper aduncum against Haemonchus contortus from sheep

Piper aduncum L., Piperaceae, has been used to treat mainly inflammatory diseases and has shown several biological activities such as insecticidal and larvicidal. The aim of this study was to analyze the chemical composition of essential oil of P. aduncum and its efficacy to egg-hatching inhibition of Haemonchus contortus from sheep. The essential oil was obtained from leaves and analysed by gas chromatography coupled to flame ionization detector and gas chromatography coupled to mass spectrometry. It was possible to characterize 22 different substances, among them monoterpenes (80.6%) and sesquiterpenes (13.9%). The major compound was identified as 1,8-cineole (55.8%). Eggs of the nematode were exposed to four concentrations of the essential oil. Levamisole phosphate was used as positive control. The essential oil showed to be effective in inhibiting H. contortus hatchability and the LC90 was calculated as 8.9 mg.ml-1. These results can point out the P. aduncum essential oil and its chemical components as potential alternative to control of H. contortus .

Vasodilator activity of the essential oil from aerial parts of Pectis brevipedunculata and its main constituent citral in rat aorta.

The essential oil of Pectis brevipedunculata (EOPB), a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%), limonene (4.7%) and α-pinene (3.4%). Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY) rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50) of 0.044% ± 0.006% and 0.093% ± 0.015% (p < 0.05), respectively. The IC50 values for citral in endothelium-intact and denuded rings were 0.024% ± 0.004% and 0.021% ± 0.004%, respectively (p > 0.05). In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively.

Effects of 3ß-acethyl tormentic acid (3ATA) on ABCC proteins activity.

Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3ß-acetyl tormentic acid (3ATA) had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors.

3ß-acetyl tormentic acid induces apoptosis of resistant leukemia cells independently of P-gp/ABCB1 activity or expression.

Chronic myeloid leukemia (CML) is a potentially fatal stem-cell cancer. P-glycoprotein (P-gp/ABCB1) activity has been described as a relevant factor in the chemotherapeutic failure and correlated to a poor prognosis in these malignancies. In the present study, we investigated the mechanism of the antineoplastic activity of 3ß-acetyl tormentic acid (3ATA), a triterpene isolated from C. lyratiloba, on Lucena-1, an MDR leukemia cell line, that overexpressed P-gp/ABCB1. Results showing that this triterpene induced DNA-fragmentation, activation of caspase-3 and cytochrome c release indicated that its activity is mediated by the activation of the intrinsic pathway of apoptosis. Interestingly, this triterpene did not interfere with P-gp/ABCB1 expression or activity, indicating that induction of death is not mediated by any effect on this protein. Moreover, the results show that none of the others triterpenes from C. lyratiloba were able to modulate the activity of P-gp/ABCB1. Together these results suggest 3ATA and the other triterpenes as a promising material for the development of anti-neoplastic drugs for leukemia and other tumors independent of P-gp/ABCB1 activity or expression.

Sedative and anticonvulsant activities of methanol extract of Dorstenia arifolia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dorstenia arifolia is a plant that has been used in the folk medicine to produce hypnotic, sedative and ansiolitic effects but the pharmacological properties have not yet been studied. In addition, the smoke of its rhizome is reputed to induce lethargic sensation. AIMS OF THE STUDY: The present study investigated possible activities of the methanol extract (ME) of Dorstenia arifolia rhizome on the central nervous system (CNS). MATERIALS AND METHODS: ME was tested for sedative, hypnotic and anticonsulsant effects using locomotor activity evaluation, pentobarbital-induced sleeping time and pentylenetetrazol (PTZ)-induced convulsion, respectively. RESULTS: Intraperitoneal administration of ME (10 and 50mg/kg) significantly decreased locomotor activity from 205.2+/-25.6 movements/min (DMSO) to 112.1+/-18.4 (P<0.05) and 114.9+/-16.9 (P<0.05), respectively. Flumazenil (10 mg/kg), an antagonist of GABA(A) receptor, prevented the ME-induced sedation. Treatment with ME (50mg/kg) significantly increased the duration of pentobarbital-induced sleeping time from 41.0+/-2.3 to 57.9+/-2.9 min (P<0.05). The latencies to seizures after intraperitoneal injection of PTZ was recorded and compared between groups. ME promoted a significant protection of PTZ-induced seizures and mortality in a dose-dependent manner. CONCLUSIONS: Our findings indicate that ME of Dorstenia arifolia rizhome has pronounced central effects, and that the sedative and anticonvulsant activities may be related to a facilitation of the GABAergic transmission.

Analgesic and anti-inflammatory properties of essential oil from Ageratum fastigiatum

The chemical composition, analgesic and anti-inflammatory properties of essential oil from Ageratum fastigiatum were investigated. The main compounds found in the essential oil were germacrene D, α-humulene and β-cedrene. The oil, with LD50 of 2.50 g/kg, inhibited the acetic acid-induced writhing at the dose of 200 mg/kg. In the formalin test, the oil inhibited the first phase (200 mg/kg) and the second phase (100 mg/kg and 200 mg/kg). In the hot plate test, after 30 and 60 min of treatment the doses of 100 and 200 mg/kg increased the reaction time. The antiedematogenic effect, reduction on the exudate volume and leukocyte mobilization were observed at the doses of 100 and 200 mg/kg. The results indicated that A. fastigiatum possessed the analgesic and anti-inflammatory properties that supported the popular medicinal use of the plant.

A composição química e as propriedades analgésica e antiinflamatória do óleo essencial de Ageratum fastigiatum foram investigadas. Os principais constituintes do óleo essencial foram germacreno D, α-humuleno e β-cedreno. O óleo, com DL50 de 2,50 g/kg, inibiu as contorções abdominais induzidas por ácido acético na dose de 200 mg/kg. No teste da formalina, o óleo inibiu a primeira fase (200 mg/kg) e a segunda fase (100 e 200 mg/kg). O tempo de latência aumentou no teste da placa quente, após 30 e 60 minutos de tratamento, nas doses de 100 e 200 mg/kg. O efeito antiedematogênico, assim como a redução do volume do exsudato e da migração leucocitária foram observados nas doses de 100 e 200 mg/kg. Os resultados indicam que o A. fastigiatum possui propriedades analgésica e antiinflamatória, o que corrobora com o uso popular da planta.

Atividade antiviral de Musa acuminata Colla, Musaceae / Antiviral activity of Musa acuminata Colla, Musaceae

O presente trabalho avalia a atividade antiviral de extratos e frações de Musa acuminata Colla, Musaceae, coletada em duas regiões do Estado do Rio de Janeiro (Petrópolis e Santo Antônio de Pádua). As inflorescências de M. acuminata apresentaram excelente atividade para os dois vírus avaliados: herpesvírus simples humano tipo 1 e herpesvírus simples humano tipo 2, ambos resistentes ao Aciclovir. Os resultados indicam que os extratos de M. acuminata testados podem constituir alvo potencial para uso em terapias antivirais.

This study evaluates the antiviral activity of extracts and fractions of Musa acuminata Colla collected in two regions of Rio de Janeiro State (Petrópolis and Santo Antônio de Pádua). The inflorescences of M. acuminata showed excellent activity for the two virus evaluated: simple human herpesvirus type 1 and simple human herpesvirus type 2, both resistant to Acyclovir. The results indicate that the tested extracts of M. acuminata can be potential target for use in antiviral therapy.

In vitro cytotoxic, antioxidant and antiviral effects of Pterocaulon alopecuroides and Bidens segetum extracts / Efeitos citotóxico, antioxidante e antiviral in vitro de extratos de Pterocaulon alopecuroides e Bidens segetum

Pterocaulon alopecuroides (Lamark) De Candolle and Bidens segetum Mart. ex Colla are two species belonging to the Asteraceae family. Extracts from those two species were evaluated to their cytotoxic, antioxidant and antiviral activities. All the extracts assayed have shown a very high cytotoxity against RBL-2H3 cell line. The antioxidant assay pointed out a really high activity of the ethyl acetate extracts for B. segetum and P. alopecuroides. This can be partially explained due to the high content of coumarins, at least for P. alopecuroides. None of the total ethanol extracts from B. segetum showed significant activity against the two strains of Herpes simplex virus (Types 1 and 2 resistant to acyclovir). P. alopecuroides ethanol extract was also inactive against the Herpes simplex virus type 1 resistant to acyclovir. However, this extract presented inhibitory activity against the Herpes simplex virus type 2 resistant to acyclovir. From the ethanol crude extract of P. alopecuroides, it was possible to isolate 7-(2',3'-dihidroxy-3'-methylbutyloxy)-6-methoxycoumarin, which was tested in the same conditions, showing a viral inhibitory rate almost twice bigger than the P. alopecuroides sample for HSV-2-ACVr. The coumarin was also active against HSV-1-ACVr. Those results provide further evidence of the importance of Pterocaulon alopecuroides and Bidens segetum as medicinal plants.

Pterocaulon alopecuroides (Lamark) De Candolle e Bidens segetum Mart. ex Colla são duas espécies pertencentes à família Asteraceae. Os extratos dessas duas espécies foram avaliados quanto às suas atividades citotóxica, antioxidante e antiviral. Todos os extratos analisados apresentaram citotoxidade muito alta contra linhagens de células RBL-2H3. O ensaio de atividade antioxidante demonstrou uma alta atividade das frações em acetato de etila de B. segetum e P. alopecuroides. Isso pode ser parcialmente explicado pelo alto conteúdo de cumarinas, ao menos para P. alopecuroides. Nenhum dos extratos etanólicos totais de B. segetum mostraram atividade significativa contra o vírus Herpes simplex (Tipos 1 e 2 resistentes ao aciclovir). O extrato etanólico de P. alopecuroides também foi inativo contra o vírus Herpes simplex tipo 1 resistente ao aciclovir. Entretanto, este extrato apresentou atividade inibitória contra o vírus Herpes simplex tipo 2 resistente ao aciclovir. Do extrato etanólico bruto de P. alopecuroides foi possível isolar a 7-(2',3'-dihidroxi-3'-metilbutiloxi)-6-metoxicumarina, a qual foi testada nas mesmas condições, demonstrando um índice de inibição viral quase duas vezes maior do que o da amostra de P. alopecuroides para HSV-2-ACVr. A cumarina tabém foi ativa contra HSV-1-ACVr. Esses resultados evidenciam a importância de Pterocaulon alopecuroides e Bidens segetum como plantas medicinais.

The lignan eudesmin extracted from Piper truncatum induced vascular relaxation via activation of endothelial histamine H1 receptors.

In Brazilian folk medicine, extracts from Piper species are used to reduce blood pressure. Previously, we demonstrated the vasodilatory activity of crude extracts from leaves of Piper truncatum explaining their possible use in the treatment of hypertension in traditional medicine. In the present study, we investigated the effects of eudesmin, a lignan isolated from hexane extract of leaves from Piper truncatum, on the contractility of rat aortas and the possible mechanisms involved in its vascular action. Eudesmin induced an intense concentration-dependent relaxation of aortic rings precontracted with phenylephrine. The concentration of eudesmin necessary to reduce phenylephrine-induced aortic contraction by 50% (IC(50)) was 10.69+/-0.67 microg/ml. Eudesmin-induced vasodilation required an intact endothelium since vascular relaxation was inhibited by mechanic removal of endothelium, and by pretreatment with nitric oxide synthase inhibitor and soluble guanylate cyclase inhibitor. Relaxation induced by eudesmin was also impaired in the presence of indomethacin and diphenhydramine, a cyclooxygenase inhibitor and an antagonist of type 1 histamine receptor (H(1)), respectively. IC(50) was increased to 18.1+/-1.8 and 18.1+/-2.6 microg/ml (P<0.05; n=6) after exposure to indomethacin and diphenhydramine, respectively. Atropine (muscarinic receptor antagonist), propranolol (beta-adrenoceptor antagonist) and glibenclamide (ATP-sensitive K(+) channel blocker) did not alter the effect of eudesmin. These results indicate that eudesmin-induced vascular relaxation in rat aorta is mediated by release of nitric oxide and prostanoid through the involvement of histamine receptor present in the endothelial cells.

The anti-allergic activity of the acetate fraction of Schinus terebinthifolius leaves in IgE induced mice paw edema and pleurisy.

Schinus is a genus of the Anacardiaceae family and contains Schinus terebinthifolius, the Brazilian pepper tree that is widely used in folk medicine. We investigate the anti-allergic activity of the ethyl acetate fraction of S. terebinthifolius Raddi (ST fraction). HPLC analysis reveled that gallic acid, methyl gallate and 1,2,3,4,6-pentagalloylglucose are the major aromatic components of the fraction. Oral pre-treatment with the ST fraction (100 mg/kg) significantly inhibited paw edema induced by compound 48/80 (100 ng/paw) and to a lesser extent, the allergic paw edema (OVA, 3 microg/paw). The ST fraction (100 and 200 mg/kg) also inhibited the edema induced by histamine (100 microg/paw), preventing mast cell degranulation and, consequently, histamine release in Wistar rat peritoneal mast cells induced by C 48/80 (5 microg/mL). This histamine inhibition was also observed after mast cell pre-treatment with both methyl gallate and 1,2,3,4,6-pentagalloylglucose (100 microg/mL), the isolated compounds from the ethyl acetate fraction. Pre-treatment with the ST fraction (100 mg/kg) significantly inhibited total leukocyte and eosinophil accumulation in pleural cavities 24 h after the intrathoracic injection of OVA (12.5 microg/cavity). This effect was related to the inhibition of CCL11/eotaxin and CCL5/RANTES in pleural lavage fluid. Pre-treatment with this fraction (100 mg/kg) failed to reduce the cell influx that was observed after LPS-injection into pleural cavity (250 ng/cavity). These findings demonstrate the anti-allergic effect of the ST fraction, which includes the inhibition of edema formation and histamine release caused by mast cell degranulation and eosinophil influx into the pleural cavity probably reflected by the decreased levels of chemokines in recovered pleural lavage fluid.

Produtos naturais de algas marinhas e seu potencial antioxidante / Natural products from marine seaweeds and their antioxidant potential

Os radicais livres e outros derivados ativos do oxigênio são inevitavelmente co-produzidos em algumas reações biológicas e exercem papel fisiológico importante. No entanto, essas espécies reativas têm sido descritas como fatores que participam diretamente dos mecanismos fisiopatológicos relacionados com a continuidade e as complicações de diversos estados patológicos como a aterosclerose, a diabetes, o câncer, a artrite reumatóide, entre outros. Dessa forma, a terapia antioxidante preveniria o desenvolvimento e a progressão dessas complicações. As algas marinhas representam uma importante fonte de substâncias antioxidantes naturais, uma vez que têm sistemas de defesas antioxidantes bem desenvolvidos. O presente trabalho é uma compilação das pesquisas realizadas sobre a atividade antioxidante de produtos naturais marinhos e extratos de algas marinhas bentônicas.

Free radicals and other reactive species of oxygen are co-produced in some biological reactions and they play important physiological role, and nevertheless they are reported as factors that take straight part in the pathophysiologic mechanism associated with continuity and complications of the several pathological process such as arteriosclerosis, diabetes mellitus, cancer, and arthritis, among others. In this way, the antioxidant therapy should prevent the development and progress of these complications. Seaweeds can be valuable source of natural antioxidant compounds since they have a well-developed antioxidant defense system. The present work is a compilation of the antioxidant activities of marine natural products and benthonic marine seaweeds crude extracts researches.