Acetylcholinesterase and butyrylcholinesterase inhibition by nectriapyrone and tryptophol isolated from endophytic fungus Phomopsis sp.

Cholinesterase (ChE) inhibitors are currently the main drugs used to treat the cognitive symptoms of Alzheimer's disease (AD). Dual cholinesterase inhibitors, that is, compounds capable of inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), are considered a new potential approach for the long-term treatment of patients with AD. We evaluated the ethyl acetate extract of Phomopsis sp., grown in liquid medium malt extract and potato dextrose (PDB), an endophyte isolated from the Brazilian medicinal plant Hancornia speciosa. The anticholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were evaluated. The extracts exhibited dual action against AChE and BuChE. The compounds isolated from these extracts, nectriapyrone (1) and tryptophol (2), showed inhibitory action on BuChE (IC50 = 29.05 and 34.15 µM respectively), being selective towards BuChE. The discovery of selective BuChE inhibitors is extremely important for the development of drugs that can be used in the treatment of patients diagnosed with AD.

RP-HPLC-DAD-MS(n) Analysis and Butyrylcholinesterase Inhibitory Activity of Barbacenia blanchetii Extracts.

High-performance liquid chromatography (HPLC) coupled to a diode-array detector (DAD) and electrospray ionization mass spectrometry (MS) was applied for the separation and identification of phenolic compounds in the n-hexane, ethyl acetate and methanol crude extract of Barbacenia blanchetii. The MS, MSn and UV data together with chemosystematic evidence allowed the structural characterization of five compounds: tricin, chrysoeriol, epi-gallocatechin, kaempferol 3-O-glucoside and caffeoylquinic acid. At the same time, these extracts were evaluated against butyrylcholinesterase using Ellman's method. All extracts inhibited BuChE in a concentration-dependent form; however, the methanol extract showed a better effect that the other extracts. These compounds have been identified previously in the Velloziaceae family, but for the first time as constituents of B. blanchetii.

Antispasmodic effect of Ocimum selloi essential oil on the guinea-pig ileum.

Ocimum selloi is an herbal species popularly used in Brazil as antispasmodic. Herein, we report the antispasmodic effect of O. selloi essential oil (OS) in segments of guinea-pig ileum. OS did not reduce the tonus of the ileum. In contrast, OS reduced the contraction induced by carbachol (100 µM), BaCl2 (0.03 M) and low- and high-K(+) concentrations (25 and 60 mM, respectively). OS shifted the concentration-response curve for calcium to the right in a parallel manner. GC/MS analysis showed that OS consists mostly of methyl chavicol (97.57%). These results suggest that OS antispasmodic effect is mediated through calcium channel blockade. In addition, OS effect and mode of action could be accounted for methyl chavicol.

Evidence of the mechanism of action of Erythrina velutina Willd (Fabaceae) leaves aqueous extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina velutina is traditionally used for sleepiness, convulsions and nervous system excitation in Brazil. Although central effects have been reported for Erythrina velutina, little is known about its mechanism of action. AIM OF THE STUDY: To investigate the pharmacological evidences of mechanism of action of Erythrina velutina leaves aqueous extract (AE). MATERIALS AND METHODS: Terminal segments of the guinea-pig ileum (n=5-8) were mounted in an organ bath and isotonic contractions were recorded. Phytochemical screening was carried out on AE. RESULTS: AE (0.025-2.50 mg/ml) produced contractile response in the guinea-pig ileum, yielding typical concentration-response curves (EC50=0.63 mg/ml). Electrically evoked contractions were significantly increased in the presence of AE. AE-elicited contractions were significantly reduced by bicuculline, tetrodotoxin, atropine, verapamil or incubation in low calcium-high potassium solution. Atropine along with verapamil abolished AE contractile response. Alkaloids, catechins, steroids, flavonols, flavononols, flavonoids, phenols, saponins, tannins, triterpenoids, and xanthones were detected in AE. CONCLUSIONS: AE contains important constituents for pharmacological activities. AE-induced contractions seem to involve GABAA receptor activation, acetylcholine release, muscarinic receptor activation, augmentation of Ca2+ entry through L-type calcium channels, and calcium release from the intracellular stores. These findings provide further support for Erythrina velutina traditional uses.

Analgesic and antidiarrheal properties of Ocimum selloi essential oil in mice.

Ocimum selloi essential oil (2, 20, and 200 mg/kg; p.o.) reduced, in a dose-dependent way, the abdominal contraction induced by acetic acid (0.6%; i.p.) and the diarrhea episodes induced by castor oil in mice. At the higher dose (200 mg/kg; p.o.), the essential oil significantly reduced intestinal transit (P<0.05) in the charcoal meal test. The main component detected in O. selloi essential oil was methyl chavicol (98%; GC and GC/MS).These effects seems to support the use of O. selloi against diarrhea, intestinal spasm and visceral pain.

Avaliação dos efeitos miorelaxante, antiespasmódico e antinociceptivo do extrato aquoso da Phoradendron piperoides (Kunt.) Trel. (Viscaceae) / Investigation on miorelaxant, antispasmodic and analgesic effects of the aqueous extract of Phoradendron piperoides

Foram investigados os efeitos miorelaxante, antiespasmódico e antinociceptivo do extrato aquoso liofilizado das folhas da Phoradendron piperoides. A toxicidade aguda também foi avaliada. No íleo isolado de cobaio, o extrato aquoso da P. piperoides (0,05 - 2,0 mg/mL) produziu relaxamento de forma concentração-dependente (IC50 = 0,114 mg/mL) e, na concentração de 1,5 mg/mL, reduziu a amplitude das contrações induzidas por carbacol (2 μM), histamina (2 μM) e BaCl2 (0,03 M) em 46,6; 38,6 e 55,3 por cento (p < 0,001), respectivamente. Em camundongos, o extrato aquoso liofilizado (100-400 mg/kg) não reduziu de forma significativa as contorções abdominais induzidas por ácido acético, não modificou o tempo de reação dos animais no teste da formalina e não aumentou o tempo de latência ao calor no teste da placa quente. No ensaio de toxicidade aguda utilizado, não foi detectada a morte de nenhum animal após tratamento com doses de até 5 g/kg (p.o.) do extrato. Em conclusão, os resultados obtidos indicam que o extrato aquoso da P. piperoides apresenta efeito antiespasmódico e baixa toxicidade aguda. O extrato, no entanto, não possui efeito antinociceptivo.

The present work evaluated the antinociceptive, miorelaxant and antispasmodic effects as well as the acute toxicity of the aqueous extract from leaves of Phoradendron piperoides. In guinea pig ileum, the plant extract (0.05 - 2.0 mg/kg) decreased the preparations basal tone in a dose-dependent manner (IC50 = 0.114 mg/mL) and it (1.5 mg/mL) reduced (p < 0.001) the contractions induced by carbachol (2 μM), histamine (2 μM) and BaCl2 (0.03M). The extract, at oral doses of 100, 200, and 400 mg/kg, did not manifest a significant antinociceptive effect in the writhing, formalin and hot-plate tests. Moreover, no animal deaths were observed in doses up to 5 g/kg. In conclusion, the aqueous extract of Phoradendron piperoides showed no antinociceptive effect and no acute toxicity in mice. Indeed, it revealed miorelaxant and antispasmodic activities that are probably miogenic and not specific for neurotransmitters.

Antinociceptive activity of Maytenus rigida stem bark.

Ethanol extract of Maytenus rigida stem bark and its fractions were assessed for antinociceptive activity in tail-flick test in rats. The activity was located in the chloroform, ethyl acetate and aq.methanol fractions. Phytochemical screening revealed that catechin was the only common class of compounds present on the ethanol extract as well as on the active fractions. 4'-Methylepigallocatechin, isolated from the ethyl acetate and aq.methanol fractions, showed antinociceptive effect in the tail-flick test (75 mg/kg; p.o.), which was reversed by the opiate antagonist naloxone (3 mg/kg; i.p.).

Antinociceptive effect and acute toxicity of the Hyptis suaveolens leaves aqueous extract on mice.

The aqueous extract of Hyptis suaveolens leaves was studied for their antinociceptive property in chemical and thermal models of nociception in mice. Oral administration of the aqueous extract (100, 200, and 400 mg/kg) dose-dependently reduced the number of writhings induced by acetic acid, decreased the licking activity of the early phase in formalin test and increased the reaction time in hot-plate test. The antinociceptive effect was significantly antagonized by naloxone (3 mg/kg; i.p.). Preliminary acute toxicity study showed that no animal death with doses up to 5 g/kg (p.o.).

Antinociceptive effect and acute toxicity of the essential oil of Hyptis fruticosa in mice.

The essential oil of the Hyptis fruticosa leaves was analyzed by GC/MS and evaluated for antinociceptive property as well as acute toxicity in mice. The essential oil, at doses of 100, 200, and 400 mg/kg (s.c.), produced significant inhibition of acetic acid-induced writhing, but did not manifest a significant effect in hot-plate test. There was no acute toxicity at doses up to 5 g/kg. Bicyclogermacrene, 1,8-cineole, alpha-pinene, and beta-caryophyllene were the major compounds detected in the essential oil.

Avaliação do efeito antinociceptivo e da toxicidade aguda do extrato aquoso da Hyptis fruticosa Salmz. ex Benth / Evaluation of the analgesic effect and acute toxicity of the aqueous extract of Hyptis fruticosa (Salmz. ex Benth.)

Este trabalho descreve o efeito antinociceptivo e a toxicidade aguda do extrato aquoso das folhas da Hyptis fruticosa Salmz. ex Benth. (Lamiaceae). O extrato aquoso liofilizado, administrado por via oral, reduziu as contorções abdominais induzidas por ácido acético (200, 400 e 500 mg/kg) e o tempo de reação dos animais na primeira fase do teste da formalina (100 mg/kg e 400 mg/kg). No teste da placa quente, o extrato aquoso aumentou o tempo de latência ao calor (100 e 200 mg/kg) tendo este efeito sido revertido pelo antagonista opióide naloxona (5 mg/kg; i.p.). No ensaio de toxicidade aguda, não foi detectada a morte de nenhum animal após tratamento com doses de até 5 g/kg (v.o.) do extrato. Em conclusão, os resultados obtidos indicam que o extrato aquoso da Hyptis fruticosa apresenta efeito antinociceptivo em camundongos e não apresenta toxicidade aguda nas doses testadas.

The antinociceptive effect and the acute toxicity of Hyptis fruticosa leaves were evaluated through the administration of its aqueous extract in mice. The extract, administered orally (200, 400, and 500 mg/kg), reduced the nociceptive response in the writhing test as well as in the early phase of the formalin test (100 and 400 mg/kg) and it increased the latency time in the hot plate test (100 and 200 mg/kg). The antinociceptive effect was reversed by naloxone (5 mg/kg, i.p.). Moreover, no animal deaths were observed in doses up to 5 g/kg. In conclusion, the aqueous extract of Hyptis fruticosa showed no acute toxicity at the evaluated doses and revealed antinociceptive effect in mice. Such effects are possibly associated with the opioid system activation.

Antinociceptive effect of Hyptis pectinata leaves extracts.

Oral administration of hexanes, chloroform, and ethyl acetate extracts of the leaves of Hyptis pectinata significantly reduced the number of writhing induced by acetic acid and increased the response to thermal stimuli in hot-plate test. Such effect was completely reversed by the opioid antagonist naloxone.

Efeito antinociceptivo e antiinflamatório do extrato aquoso da entrecasca de Coutarea hexandra Schum. (Rubiaceae) / Antinociceptive and anti-inflammatory properties of Coutarea hexandra barks aqueous extract Schum. (Rubiaceae)

No estado de Sergipe, o chá da entrecasca de Coutarea hexandra Shum. (Rubiaceae) é popularmente utilizado no combate à dor e à inflamação. Estes usos etnofarmacológicos vieram motivar os estudos sobre os efeitos antinociceptivo e antiinflamatório, bem como sobre a toxicidade aguda do extrato aquoso liofilizado da entrecasca de Coutarea hexandra. Doses orais do extrato aquoso significativamente reduziram as contorções abdominais induzidas por ácido acético, aumentaram o tempo de latência ao calor no teste da placa quente, reduziram o edema de pata induzido por carragenina e, na segunda fase do teste da formalina, também reduziram a resposta dos animais à formalina. O efeito detectado no teste da formalina não foi revertido por naloxona ou cafeína. Nos ensaios de toxicidade aguda, não foi observada a morte de nenhum animal até a dose de 5 g/kg. Em conclusão, o extrato aquoso da entrecasca de C. hexandra possui efeitos antiinflamatório e antinociceptivo e não apresenta toxicidade aguda em camundongos. O efeito antinociceptivo não está relacionado à ativação dos sistemas opióide e adenosina e, ao menos parcialmente, é decorrente da atuação do extrato aquoso em nível central.

The aqueous extract of Coutarea hexandra Shum. (Rubiaceae) is extensively used on local folk medicine as anti-inflammatory and antinociceptive. In view of these facts, it was of our interest to evaluate the anti-inflammatory and antinociceptive activities. Its acute toxicity was also evaluated. The aqueous extract of Coutarea hexandra reduced acetic acid-induced writhing, increased the latency in the hot plate test, and reduced the second phase nociceptive response in the formalin test. Neither naloxone nor caffeine reversed aqueous extract of Coutarea hexandra effect in the second phase of the formalin test. The aqueous extract of Coutarea hexandra also reduced the rat paw edema induced by carrageenan. There was no animal death with doses up to 5 g/kg in the acute toxicity assays. These results showed that aqueous extract of C. hexandra has low acute toxicity, as well as, anti-inflammatory and antinociceptive effects, substantiating its popular usage. The antinociceptive effect seems to involve a central component, although it is not directly related to the opioid and adenosine systems.