Neuropharmacological and acute toxicological evaluation of ethanolic extract of Allamanda cathartica L. flowers and plumieride.

Psychiatric diseases affect more than 350 million people all over the world, and medicinal plants have been considered the basis for pharmacological research. The study investigates the anticonvulsant and antidepressant-like activities and acute toxicological effects of ethanolic extract of Allamanda cathartica flowers, and plumieride. The extract was analyzed by HPLC and plumieride was isolated. Toxicity studies were carried out on females Wistar rats (2000 mg/kg). Toxicity was evaluated by measuring biochemical parameters and conducting histopathological analysis. For pharmacological evaluation different doses of the extract (100, 150 and 300 mg/kg, p.o.) and plumieride (0.5, 1 and 2 µg/kg, i.p.) were administered before the Forced-Swimming Test (FST), pentylenetetrazole seizure test (PTZT) or Tail-Suspension Test (TST) in mice. Furthermore, hemolytic activity, cytotoxicity and micronucleus test were performed. In addition, mutagenicity and reproductive/developmental toxicity were estimated by TEST-software analysis. Data show that both treatments induce significant antidepressive-like effect in FST and TST, but not anticonvulsant effect. The effect of plumieride last up to 4 h after treatment. No signs of toxicity, mutagenicity, cytotoxicity or hemolytic activity were observed. The TEST-software demonstrated that plumieride present reproductive/developmental toxicity. Together, the data obtained show that the flowers extract and plumieride present antidepressant-like effect and did not present signals of acute toxicity.

Spray-dried O-carboxymethyl chitosan as potential hydrophilic matrix tablet for sustained release of drug.

OBJECTIVE: The aim of the present investigation was to evaluate the use of spray-dried O-carboxymethyl chitosan (OCMCS) as potential hydrophilic matrix excipient for sustained release of drug. METHODS: The polymer was synthesized from chitosan, then spray-dried and characterized. Tablets with different OCMCS concentrations (80, 50, 30, 5 and 2% w/w), containing diltiazem (DTZ) as model drug, were prepared for direct compression (DC) and after the wet granulation method (WG). RESULTS: The spray-dried OCMCS powder was spherical, with a smooth surface and an average size of 2.2 µm. The tablets prepared for WG disintegrated in time less than 30 min. The tablets obtained for DC presented high retention of the drug, with zero order or Higuchi release kinetic. There was a direct relationship between the OCMCS concentration and the release ratio, swelling degree and water uptake behavior. DC tablets containing 80% OCMCS presented behavior as an effective swelling-control system. The DC tablets with 5% OCMCS showed a similar release profile at formulations with 30% HPMC. CONCLUSION: Spray-dried OCMCS showed great potential as hydrophilic matrices for drug-sustained release.

Aleurites moluccana (L.) Willd. Leaves: Mechanical Antinociceptive Properties of a Standardized Dried Extract and Its Chemical Markers.

Seeking to develop a new analgesic phytomedicine, a spray-dried extract (SDE) of Aleurites moluccana (L.) Willd. leaves was developed in scale up (5 kg). The SDE was standardized at 3% w/w in relation to the flavonoid 2''-O-rhamnosylswertisin. The SDE batches were evaluated in relation to their physical, physiochemical, and pharmacological characteristics. The results demonstrated the reproducibility of the scale up SDE process which, when dosed orally, reduced carrageenan-induced mechanical hypernociception, with an ID(50)% of 443 mg/kg. Similar results were obtained with animals injected with complete Freund's adjuvant (CFA), in which SDE caused inhibition of 48 ± 4%. SDE was effective in preventing prostaglandin E2 (PGE2)-induced mechanical hypernociception (inhibition of 26 ± 10% and 33 ± 3%, at 250 and 500 mg/kg, respectively). Swertisin and 2''-O-rhamnosylswertisin isolated from the own extract were effective in inhibiting the hypernociceptive response induced by carrageenan (70 ± 2% and 50 ± 5%, resp.). Furthermore, 2''-O-rhamnosylswertisin was capable of significantly inhibiting the mechanical sensitization induced by CFA or PGE2, with inhibitions of 25 ± 3% and 94 ± 6%, respectively. These results suggest that the effects of SDE are related, at least in part, to the presence of these flavonoids.

Nanoemulsion as a carrier to improve the topical anti-inflammatory activity of stem bark extract of Rapanea ferruginea.

The aim of this study was to develop nanoemulsion containing soft extract of stem bark of Rapanea ferruginea to improve the topical delivery and anti-inflammatory activity. The extract of R. ferruginea stem bark was incorporated into the oily phase of the nanoemulsion by the method of phase inversion at low energy. The developed nanoemulsion had an average droplet size of 47.88±8.20 nm and a polydispersibility index of 0.228. Uniformity of size, spherical shape of droplet, and absence of clusters were confirmed by transmission electronic microscopy. The zeta potential was -34.7±1.15 mV. The nanoemulsion showed a moderate degree of skin irritation in the agarose overlay assay in vitro. The content of the extract markers, myrsinoic acids A and B, was 54.10±0.08 and 53.03 µg/g in the formulation, respectively. The formulation demonstrated pseudoplastic and thixotropic rheological behavior. In vitro release of chemical markers was controlled by diffusion mechanism. An extract-loaded nanoemulsion showed a topical anti-inflammatory activity in a croton oil-induced edema ear model, with a decrease in tumor necrosis factor release and myeloperoxidase activity. The nanoemulsion was 160% more efficient than the conventional cream containing 0.13% of the extract. The nanoemulsion showed suitable properties as a carrier for topical use of R. ferruginea extract and the approach for improving the topical anti-inflammatory activity.

Aleurites moluccana and its main active ingredient, the flavonoid 2″-O-rhamnosylswertisin, have promising antinociceptive effects in experimental models of hypersensitivity in mice.

This study investigated the antinociceptive effect of Aleurites moluccana dried extract (DE; 125 to 500 mg/kg, p.o.) and the isolated flavonoid 2″-O-rhamnosylswertisin (5 to 50.6 µmol/kg, p.o.) using different models of long-lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse the mechanisms through which A. moluccana exerted its effects. A. moluccana DE inhibited complete Freund's adjuvant (CFA)-induced mechanical nociception. It was also evidenced by a reduction of sensitization in the contralateral hindpaw. The extract reversed the mechanical hypersensitivity of partial ligation of sciatic nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid, dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE antinociceptive effects. A single dose of 2″-O-rhamnosylswertisin inhibited the carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound caused expressive antinociception in PLSN-mice, with inhibition value greater than obtained with gabapentin. Oral treatment with the extract or the isolated compound attenuated the neutrophil migration and IL-1ß levels following carrageenan injection. Of note, A. moluccana DE did not interfere with thermal sensitivity in healthy mice. The absence of side effects, including interference in locomotor activity, motor performance in animals treated with the extract, showed excellent potential for the therapeutic use of this medicinal plant in treating persistent pain in humans.

Development and validation of an HPLC-PDA method for the determination of myrsinoic acid B in the extracts of Rapanea ferruginea Mez.

New, simple, rapid and precise HPLC-PDA method has been developed and validated for quantification of biomarker myrsinoic acid B in stem bark extracts of Rapanea ferruginea Mez. The method employs a Phenomenex C18 column (250 mm × 4.6mm I.D., 5 µm) with acetonitrile:methanol:water (pH 2.6 with phosphoric acid) at 48:30:22 as mobile phase, at a flow rate of 0.7 mL min(-1) and photo diode array (PDA) detection at 270 nm. The validation data show that the method is specific, accurate, precise and robust. The method was linear, over a range of 5-100.0 µg mL(-1), with a limit of detection of 0.369 µg mL(-1) and limit of quantification of 1.233 µg mL(-1). The method has also shown consistent recoveries (average of 101.3% and 0.12% RSD) of the biomarker, with low intra and inter-day relative standard deviation (1.26% and 1.62%, respectively). The evaluated hydroethanolic extract and dry extract presented MAB values of 63.53 and 36.07 mg g(-1), respectively.

Análise morfoanatômica das partes aéreas de Wedelia paludosa DC. (Acmela brasiliensis, Sphagneticola trilobata), Asteraceae / Morphoanatomic analysis of aerial parts of Wedelia paludosa DC. (Acmela brasiliensis, Sphagneticola trilobata), Asteraceae

O presente trabalho teve por objetivo o estabelecimento de parâmetros para análise morfo-anatômica das partes aéreas (caule e folhas) da planta Wedelia paludosa DC., Asteraceae. A droga vegetal e o respectivo pó foram submetidos às análises macro e microscópica após preparação de lâminas semi-permanentes de cortes transversais e paradérmicos. O pó foi analisado após diafanização com cloral hidratado. É uma planta herbácea com caule castanho-avermelhado, folhas opostas, curto-pecioladas e membranáceas, apresentando pêlos nas duas faces, estreitada em direção à base acima do meio provida de dois pequenos lobos laterais e um terminal, maior e denteado. A planta apresenta secção circular de caule, que em crescimento primário, possui epiderme, colênquima angular, parênquima cortical e cilindro vascular, assim como oxalato de cálcio (várias drusas e alguns cristais prismáticos). A folha é simples, contendo tricomas tectores e estômato anomocítico. O mesofilo possui organização dorso-ventral e a nervura central, em corte transversal, apresenta-se côncavo-convexo com três feixes colaterais e presença de drusas de oxalato de cálcio nas células parenquimáticas. No pó obtido da droga vegetal foram verificadas as mesmas estruturas microscópicas observadas na droga vegetal rasurada. Os parâmetros morfo-anatômicos estabelecidos neste trabalho permitem o controle de qualidade macro e microscópico da planta tanto rasurada como na forma de pó.

This study aimed to establish parameters for morphoanatomical analysis of the aerial parts (stem and leaves) of the plant Wedelia paludosa DC., Asteraceae. The drug and its respective powder were characterized by macro and microscopic analysis after obtaining semi-permanent lamina of transverse and paradermal sections. The powder was analyzed after being cleared with chloral hydrate. It is an herbaceous plant with reddish-brown stems, opposite leaves, short-petiolated and membranous, with hair on both faces, narrowed towards the base up the middle provided with two small lateral lobes and a, large and jagged terminal. The plant has circular cross-section of stem, in which the primary growth, has epidermis, angular collenchyma, cortical parenchyma and vascular cylinder, as well as calcium oxalate (several clusters and some prismatic crystals). The leaf is simple, containing trichomes and stomata. The mesophyll has dorsiventral organization and the midrib, in cross section presents concave-convex face with three bundles and presence of calcium oxalate in parenchymal cells. In the powder was found the same structures observed in microscopic drug erased. The morphoanatomical parameters established in this work allow the macro and microscopic quality control of power and sectioned drug.