Anti-allodynic and anti-oedematogenic properties of the extract and lignans from Phyllanthus amarus in models of persistent inflammatory and neuropathic pain

This study investigated the anti-allodynic and anti-oedematogenic effects of the hexanic extract, lignan-rich fraction and purified lignans from a plant used in the traditional medicine, Phyllanthus amarus, in the inflammatory and neuropathic models of nociception. The hexanic extract inhibited the allodynia and the oedema induced by the intraplantar injection of complete Freund's adjuvant (CFA). The inhibition observed was 76 +/- 7% (ipsilateral paw), 64 +/- 7% (contralateral paw), and 41 2% (oedema). Otherwise, the lignan-rich fraction or the pure lignans did not affect CFA-induced allodynia. Administered chronically, the lignan fraction reduced CFA-induced paw oedema (39 +/- 9%). When evaluated in the model of neuropathic pain caused by partial ligation of sciatic nerve, the hexanic extract inhibited the mechanical allodynia (77 +/- 7%), with a similar efficacy to the gabapentin (71 +/- 10%). The anti-allodynic effects of hexanic extract of P. amarus seem not to be associated with the impairment of motor co-ordination or with the development of tolerance. Finally, the treatment with hexanic extract inhibited the increase of myeloperoxidase activity, either following intraplantar injection of CFA or after sciatic nerve injury. It is concluded that, apart from its anti-inflammatory actions, which are probably linked to the presence of lignans, another as yet unidentified active principle(s) present in the hexanic extract of P. amarus produces pronounced anti-allodynia in two models of inflammatory and neuropathic pain. Considering that few drugs are currently available for the treatment of chronic pain, especially of the neuropathic type, the present results may have clinical relevance and open new possibilities for the development of new anti-allodynic drugs. (C) 2003 Elsevier B.V All rights reserved.4784170014515

Composition and Evaluation of the Anti-Inflammatory and Anticancer Activities of the Essential Oil from Annona sylvatica A. St.-Hil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The essential oil from the leaves of Annona sylvatica (EOAS) was extracted by hydrodistillation, and the analysis was performed by gas chromatography-mass spectrometry. The main compounds identified in the EOAS were sesquiterpenes, such as hinesol, z-caryophyllene, beta-maaliene, gamma-gurjunene, silphiperfol-5-en-3-ol, ledol, cubecol-1-epi, and muurola-3,5-diene. Oral administration of the EOAS (20 and 200 mg/kg) and subcutaneous injection of dexamethasone (0.5 mg/kg, reference drug) significantly inhibited carrageenan- and complete Freund's adjuvant-induced mouse paw edema. The anticancer activity the EOAS showed growth inhibitory activity on all cell lines when administered in a high concentration. The EOAS inhibited the growth of human cancer cell lines with GI(50) values in the range of 36.04-45.37 mu g/mL on all of the cell lines tested. This work describes for the first time the anti-inflammatory and anticancer effects of the essential oil of A. sylvatica and its composition. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side-effects, the present results may have clinical relevance and open new possibilities for the development of novel anti-inflammatory and anticancer drugs.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.1612025Fundect (Brazil, MS)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus - Evidence for interaction with platelet activating factor receptor

Previous studies have shown that the extracts obtained from Phyllanthus amarus, and some of the lignans isolated from it, exhibit pronounced antiinflammatory properties. In the present study, we have assessed whether the antiinflammatory actions of these lignans can be mediated by interaction with platelet activating factor (PAF) receptor or interference with the action of this lipid. The local administration of nirtetralin, phyltetralin or niranthin (30 nmol/paw), similar to WEB2170 (a PAY receptor antagonist, 30 nmol/paw), significantly inhibited PAF-induced paw oedema formation in mice. The extracts of P. amarus (100 mu g/ml) and niranthin (30 mu M), but not nirtetralin or phyltetralin (30 mu M), decreased the specific binding of [H-3]-PAF in mouse cerebral cortex membranes. Furthermore, both niranthin and WEB2170 displaced, in a concentration-dependent manner, the [H-3]-PAF binding sites. The mean IC50 values from these effects were 6.5 mu M and 0.3 mu M, respectively. Additionally, both niranthin and WEB2170 (30 nmol/paw) inhibited the increase of myeloperoxidase activity induced by PAF injection in the mouse paw. When assessed the mouse model of pleurisy induced by PAT, pretreatment with niranthin (100 mu mol/kg, p.o.) or WEB2170 (1.7 mu mol/kg, i.p.) significantly inhibited PAF-induced protein extravasations. Moreover, in the rat model of PAF-induced allodynia, both niranthin (30 nmol/paw) and WEB2170 (30 nmol/paw) treatment significantly inhibited PAF-induccd allodynia. In addition, niranthin had a rapid onset and long-lasting antiallodynic action when compared with WEB2170. Collectively, the present findings suggest that niranthin exhibits anti inflammatory and antiallodynic actions which are probably mediated through its direct antagonistic action on the PAF receptor binding sites. (c) 2006 Elsevier B.V. All rights reserved.5464169918218

Chemical composition and cytotoxic activity of the essential oil from the leaves of Casearia lasiophylla

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The essential oil obtained by hydrodistillation from fresh leaves of Casearia lasiophylla Eichler, Salicaceae, was analyzed by gas capillary (GC/FID and GC/MS). The cytotoxicity of the leaves essential oil was tested in vitro against U251 (glioma), UACC-62 (melanoma), MCF-7 (breast), NC1-ADR/RES (ovarian-resistant), NCI-H460 (lung), PC03 (prostate), OVCAR-3 (ovarian), HT-29 (colon) and K562 (leukemia) human cancer cells and against VERO (no cancer cell). The yield of oil was 0.02%. Fifty two compounds were identified, representing 87.1% of the total of the oil. The main components were identified as germacrene D (18.6%), beta-caryophyllene (14.7%), delta-cadinene (6.2%), and alpha-cadinol (5.4%). The oil exhibited antiproliferative activity against all cell lines (TGI<100 mu g/mL), with exception of NCI-H460 cell line (TGI 191.31. mu g/mL). The highest activity was observed against UACC-62 (TGI 7.30 mu g/mL), and K562 (TGI 7.56 mu g/mL) cell lines. The observed activity could be related to high content of germacrene D and. beta-caryophyllene, compounds known as cytotoxic.215864868Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAEPEX-UNICAMPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: Evidence for the inhibition of angiotensin converting enzyme

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Aim of the study: Previous studies have shown that the extracts obtained from Tropaeolum majus L exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE). Methods and methods: Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10-300 mg/kg) and TMLR (12.5-100 mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100 mg/kg) and xylazine (20 mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5-4 mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF. Results: The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3 h after the administration of the extract. Additionally, the intravenous administration of ISQ but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90 min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats. Conclusion: Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE. (C) 2010 Elsevier Ireland Ltd. All rights reserved.1342363372Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)DEGPP/UNIPARFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Diuretic and potassium-sparing effect of isoquercitrin-An active flavonoid of Tropaeolum majus L.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Aim of the study: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. Material and methods: Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100 mg/kg) and isoquercitrin (5-10 mg/kg), as well the reference drug hydrochlorothiazide (10 mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na(+)) and potassium (K(+)) electrolytes were measured in the urine of saline-loaded animals. Results: The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na(+).. Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na(+) and K(+) had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. Conclusion: This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin. (C) 2010 Elsevier Ireland Ltd. All rights reserved.1342210215Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)DEGPP/UNIPARFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES