Aline Cavalcanti de Queiroz

The Antinociceptive and Anti-Inflammatory Activities of Caulerpin, a Bisindole Alkaloid Isolated from Seaweeds of the Genus Caulerpa

The antinociceptive and anti-inflammatory activity of caulerpin was investigated. This bisindole alkaloid was isolated from the lipoid extract of Caulerpa racemosa and its structure was identified by spectroscopic methods, including IR and NMR techniques. The pharmacological assays used were the writhing and the hot plate tests, the formalin-induced pain, the capsaicin-induced ear edema and the carrageenan-induced peritonitis. Caulerpin was given orally at a concentration of 100 μmol/kg. In the abdominal constriction test caulerpin showed reduction in the acetic acid-induced nociception at 0.0945 μmol (0.0103–1.0984) and for dypirone it was 0.0426 μmol (0.0092–0.1972). In the hot plate test in vivo the inhibition of nociception by caulerpin (100 μmol/kg, p.o.) was also favorable. This result suggests that this compound exhibits a central activity, without changing the motor activity (seen in the rotarod test). Caulerpin (100 μmol/kg, p.o.) reduced the formalin effects in both phases by 35.4% and 45.6%, respectively. The possible anti-inflammatory activity observed in the second phase in the formalin test of caulerpin (100 μmol/kg, p.o.) was confirmed on the capsaicin-induced ear edema model, where an inhibition of 55.8% was presented. Indeed, it was also observed in the carrageenan-induced peritonitis that caulerpin (100 μmol/kg, p.o.) exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 48.3%. Pharmacological studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive and anti-inflammatory actions and also to identify other active principles present in Caulerpa racemosa.

Antinociceptive and Anti-Inflammatory Activity from Algae of the Genus Caulerpa

Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME), acetate (AE), hexanic (HE) and chloroform (CE) extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o.) did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in the Caulerpa species.

Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates.

In this paper we report the design, synthesis and pharmacological evaluation of a series of N-phenyl-acetamide sulfonamide derivatives (5a-g), planned by structural modification on the prototype paracetamol (1). In this series (5a-g), compound LASSBio-1300 (5e; ID(50)=5.81 micromol/kg) stands out as a new non-hepatotoxic analgesic drug candidate. The increase of area, volume and electrostatic potential of paracetamols analogues seems to be beneficial to the analgesic activity. Unlike paracetamol (1) and the other analogues (5a, 5d-g), compounds 5b and 5c presented an important anti-hypernociceptive activity associated to inflammatory pain.

Antinociceptive activities of crude methanolic extract and phases, n-butanolic, chloroformic and ethyl acetate from Caulerpa racemosa (Caulerpaceae)

Neste estudo, tentamos identificar a atividade antinociceptiva do extrato metanolico bruto e das fases n-butanolica, cloroformica e acetato de etila provenientes da alga Caulerpa racemosa. Esta alga e cosmopolita no mundo, principalmente em regioes tropicais. O extrato metanolico bruto e as fases n-butanolica, cloroformica e acetato de etila foram administrados por via oral, na concentracao de 100 mg/kg. Estes foram capazes de reduzir a nocicepcao produzida pelo acido acetico, sendo 47,39%, 70,51%, 76,11% e 72,24%, respectivamente. No ensaio da placa quente as fases cloroformica e acetato de etila foram ativas neste modelo. Na fase neurogenica do teste de formalina, foi observado que o extrato metanolico bruto (51,77%), fase n-butanolica (35,12%), fase cloroformica (32,70%) e indometacina (32,06%) foram eficazes em inibir a resposta nociceptiva. Na fase inflamatoria, apenas a fase acetato de etila (75,43%) e indometacina (47,83%) foram capazes de inibir significativamente a resposta nociceptiva. Com base nestes dados, podemos sugerir que o a fase acetato de etila apresenta um significativo efeito anti-inflamatorio, cuja potencia ainda nao foi determinada. No entanto, estudos farmacologicos e quimicos serao necessarios, a fim de caracterizar o mecanismo responsavel pela acao antinociceptiva e tambem para identificar outros principios ativos presentes na alga Caulerpa racemosa.

Synthesis, Leishmanicidal Activity and Theoretical Evaluations of a Series of Substituted bis-2-Hydroxy-1,4-Naphthoquinones

A series of eight substituted bis-2-hydroxy-1,4-naphthoquinone derivatives was synthesized through lawsone condensation with various aromatic and aliphatic aldehydes under mild acidic conditions. The title compounds were evaluated for antileishmanial activity in vitro against Leishmania amazonensis and Leishmania braziliensis promastigotes; six compounds showed good activity without significant toxic effects. The compound with the highest activity was used for an in vivo assay with Leishmania amazonensis.

Antileishmanial Phenylpropanoids from the Leaves of Hyptis pectinata (L.) Poit

Hyptis pectinata, popularly known in Brazil as “sambacaitá” or “canudinho,” is an aromatic shrub largely grown in the northeast of Brazil. The leaves and bark are used in an infusion for the treatment of throat and skin inflammations, bacterial infections, pain, and cancer. Analogues of rosmarinic acid and flavonoids were obtained from the leaves of Hyptis pectinata and consisted of two new compounds, sambacaitaric acid (1) and 3-O-methyl-sambacaitaric acid (2), and nine known compounds, rosmarinic acid (3), 3-O-methyl-rosmarinic acid (4), ethyl caffeate (5), nepetoidin A (6), nepetoidin B (7), cirsiliol (8), circimaritin (9), 7-O-methylluteolin (10), and genkwanin (11). The structures of these compounds were determined by spectroscopic methods. Compounds 1–5, and 7 were evaluated in vitro against the promastigote form of L. braziliensis, and the ethanol extract. The hexane, ethyl acetate, and methanol-water fractions were also evaluated. The EtOH extract, the hexane extract, EtOAc, MeOH:H2O fractions; and compounds 1, 2 and 4 exhibited antileishmanial activity, and compound 1 was as potent as pentamidine. In contrast, compounds 3, 5, and 7 did not present activity against the promastigote form of L. braziliensis below 100 µM. To our knowledge, compounds 1 and 2 are being described for the first time.

Antinociceptive and anti-inflammatory effects of flavonoids PMT1 and PMT2 isolated from Piper montealegreanum Yuncker (Piperaceae) in mice

In this study, we identified the antinociceptive and anti-inflammatory effects of two flavonoids (PMT1 and PMT2) from Piper montealegreanum. The antinociceptive effect was evaluated using the classical tests: acetic acid-induced writhing, formalin and hot plate test. PMT1 and PMT2 (0.1, 1, 30 and 100 μmol/kg, i.p.) reduced the writhings, with an ID50 of 0.58 and 0.44 μmol/kg, respectively. Moreover, these flavonoids (100 μmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin test, but only PMT2 was active in the inflammatory phase. However, PMT1 and PMT2 (100 μmol/kg, i.p.) did not increase the latency time of the animals in the hot plate. In order to evaluate the anti-inflammatory effect of these flavonoids, capsaicin-induced ear oedema was carried out. Both flavonoids (100 μmol/kg, i.p.) were active in this model. These results suggest that PMT1 and PMT2 have antinociceptive and anti-inflammatory activities.

Antileishmanial Activity of Medicinal Plants Used in Endemic Areas in Northeastern Brazil

This study investigates the leishmanicidal activity of five species of plants used in folk medicine in endemic areas of the state of Alagoas, Brazil. Data were collected in the cities of Colonia Leopoldina, Novo Lino, and União dos Palmares, Alagoas state, from patients with cutaneous leishmaniasis (Leishmania amazonensis) who use medicinal plants to treat this disease. Plants extracts were tested at a concentration of 1–100 μg/mL in all experiments, except in an assay to evaluate activity against amastigotes, when 10 μg/mL was used. All plants extracts did not show deleterious activity to the host cell evidenced by LDH assay at 100, 10, and 1 μg/mL after 48 h of incubation. The plants extracts Hyptis pectinata (L.) Poit, Aloe vera L., Ruta graveolens L., Pfaffia glomerata (Spreng.) Pedersen, and Chenopodium ambrosioides L. exhibited direct activity against extracellular forms at 100 μg/mL; these extracts inhibited growth by 81.9%, 82.9%, 74.4%, 88.7%, and 87.4%, respectively, when compared with promastigotes. The plants extracts H. pectinata, A. vera, and R. graveolens also significantly diminished the number of amastigotes at 10 μg/mL, inhibiting growth by 85.0%, 40.4%, 94.2%, and 97.4%, respectively, when compared with control. Based on these data, we conclude that the five plants exhibited considerable leishmanicidal activity.

Antinociceptive and anti-inflammatory activities of the ethanolic extract, of fractions and of epicatechin isolated from the stem bark of Ximenia americana L. (Oleacaceae)

The antinociceptive and anti-inflammatory actions of the ethanolic extract, fractions and epicatechin (XM-Catechin) isolated from the ethanoic extracts of bark of Ximenia americana L. were determined utilizing in vivo models such as acetic acid-induced writhing, the formalin test, hot plate test, zymosan-induced peritonitis and in vitro cyclooxygenase inhibition assay. The writhing test revealed inhibitory effects. The formalin test demonstrated an antinociceptive effect in both early and late phases by XM-catechin, while the chloroform fraction showed a lower antinociceptive effect at the early phase. The aqueous fraction and ethanolic extract caused significant inhibition at the late phase. Treatment of mice with XM-catechin or with the ethyl acetate fraction had no central antinociceptive effect in the hot plate test. Anti-inflammatory effects were determined for zymosan-induced peritoneal inflammation and the data indicated that XM-catechin, the hydromethanol fraction, the ethanol extract and the ethyl acetate fraction reduced the number of recruited cells. These results demonstrate that the extract, fractions and XM-Catechin produce antinociceptive and anti-inflammatory responses. According to the results obtained in the cyclooxygenase inhibition assays, the observed effects are related to inhibition of COX-1 and COX-2. The biological actions demonstrated in the present study support the ethnomedicinal use of this plant.