Constituents and antiulcer effect of Alchornea glandulosa: Activation of cell proliferation in gastric mucosa during the healing process

Alchornea glandulosa (Euphorbiaceae) is a plant used in folk medicine as an antiulcer agent. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose-dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (35%) in relation to the control group. Pretreatment of mice with AG (500, 1000 mg/kg, p.o.) showed dose-dependent activity and significantly decreased the severity of lesions caused by HCl/ethanol and by non steroidal anti inflammatory drug-induced gastric lesions. Pretreatment with AG also induced antisecretory action via local and systemic routes and a significant decrease in the total gastric acid content. The gastroprotective effects of AG involved the participation of nitric oxide and increased levels of endogenous sulfhydryl compounds, which are defensive mechanisms of the gastrointestinal mucosa against aggressive factors. The ability of AG to heal gastric ulcers was evaluated after 14 consecutive days of treatment. The results showed that single oral administrations of AG (250 mg/kg/once daily) potently stimulates gastric epithelial cell proliferation that contributes to the accelerated healing of gastric ulcers induced by acetic acid. In addition, no subacute toxicity (body weight gain, vital organs, and serum biochemical parameters) was observed during treatment with AG. Phytochemical investigation of AG led to the isolation of myricetin-3-O-alpha-L-rhamnopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin, amentoflavone, methyl gallate, gallic acid, and pterogynidine. We also established the phytochemical profile of AG with the quantification of total phenolic compounds. These compounds may contribute to the observed antiulcerogenic effects of AG.

Studies on anti-allergic constituents in the leaves and stems of Anchietia salutaris var. martiana (Violaceae)

The anti-allergic active fractionation of hexane extracts of the leaves and stems of Anchietia salutaris,ar. martiana (family Violaceae) nas performed by monitoring their activities with an in vitro bioassay system measuring the inhibitory effects on induced histamine release from guinea pig lung cells. Three known pentacyclic triterpenes (friedelin, alpha-amyrin, beta-amyrin) were isolated, but these compounds were inactive. Aliphatic hydrocarbons and methyl esters of fatty acids (palmitic, oleic, linoleic, linolenic acids) were detected in active fractions. All compounds isolated were detected for the first time in this medicinal plant.

Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L.

Citrus aurantium L. is commonly used as an alternative treatment for insomnia, anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v) extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and final aqueous (AF) fractions were obtained from HE by successive partitions. Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these preparations 30 min before the experiments for the evaluation of the sedative/hypnotic activity (sleeping time induced by sodium pentobarbital-SPB: 40 mg/kg, i.p.), anxiolytic activity (elevated plus maze-EPM) and anticonvulsant activity (induced by pentylenetetrazole-PTZ: 85 mg/kg, se or by maximal electroshock-MES: 50 mA, 0.11s, corneal). The results showed that EOP (0.5 g/kg) increased the latency period of tonic seizures in both convulsing experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg increased the sleeping time induced by barbiturates and the time spent in the open arms of the EPM. Specific tests indicated that the preparation, in both doses used, did not promote deficits in general activity or motor coordination. HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but were able to enhance the sleeping time induced by barbiturates. The results obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation model, are in accord with the ethnopharmacological use of Citrus aurantium L., which could be useful in primary medical care, after toxicological investigation.

Influence of compression forces on tablets disintegration by AC Biosusceptometry

Analysis of physical phenomena that occurs during tablet disintegration has been studied by several experimental approaches; however none of them satisfactorily describe this process. The aim of this study was to investigate the influence of compression force on the tablets by associating the AC Biosusceptometry with consolidated methods in order to validate the biomagnetic technique as a tool for quality control in pharmaceutical processes.Tablets obtained at five compression levels were submitted to mechanical properties tests. For uncoated tablets, water uptake and disintegration force measurements were performed in order to compare with magnetic data. For coated tablets, magnetic measurements were carried out to establish a relationship between physical parameters of the disintegration process. According to the results, differences between the compression levels were found for water uptake, force development and magnetic area variation measurements. ACB method was able to estimate the disintegration properties as well as the kinetics of disintegration process for uncoated and coated tablets. This study provided a new approach for in vitro investigation and validated this biomagnetic technique as a tool for quality control for pharmaceutical industry. Moreover, using ACB will also be possible to test these parameters in humans allowing to establish an in vitro/in vivo correlation (IVIVC). (C) 2007 Elsevier B.V. All rights reserved.

Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia amara L. (Simaroubaceae)

Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is widely used in Caribbean folk medicine and in some northern states of Brazil for the treatment of gastric ulcers. This plant is a source of numerous compounds including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100% EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000 mg/kg intraperitoneally, caused neither toxicity or death. In the indomethacin[bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%, respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60, 82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre-treatment with a single intraduodenal administration of 100 mg/kg of each extract, only 70% EtOH did not change the biochemical parameters of gastric juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content, increased pH values and decreased acid output. We also determined the antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25 mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous amount in the gastric stomach content was also evaluated. All extracts showed significant increases (p<0.05) of free mucous. This effect was abolished when the animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated by the administration of HEX extracts by the oral route (100 mg/kg). Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this effect was abolished with prior administration of indomethacin. We concluded that Quassia amara is a probable source for a new drug to treat gastric ulcers, and the mechanism of its activity relates to cytoprotective factors, such as mucous and prostaglandins, but there is still the possibility that antisecretory activity is involved in its antiulcerogenic effect.

Propolis effect on streptozotocin-induced diabetic rats

Propolis is one of the hive products that has been used extensively in folk medicine, due to its several biological and pharmacological properties. Besides, propolis-containing products have been intensely marketed by the pharmaceutical industry and health-food stores. This work was carried out in order to investigate whether propolis treatment could revert the metabolic alterations of streptozotocin-induced diabetic rats. Animals were kept in metabolic cages and diabetes was induced by a single dose of streptozotocin (35 mg/kg, IV). After a week, rats with glycemia higher than 230 mg/dL were divided into two groups and treated with ethanolic extract of propolis (10 and 90 mg/kg, PO) for seven days. Glycemia and free fatty acids were determined, as well as food and water intake, body weight and urine volume were registered weekly. Data showed no significant differences in the analyzed variables. Based on these results, one may conclude that propolis had no effects after diabetes establishment, in our conditions assays. Further assays with different concentrations of propolis and periods of administration should be carried out in order to evaluate its therapeutic potential in this disease.

Propolis: Is there a potential for the development of new drugs?

Introduction: Propolis has plenty of biological and pharmacological properties and its mechanisms of action have been widely investigated in the last years, using different experimental models in vitro and in vivo. Researchers have been interested in the investigation of isolated compounds responsible for propolis action; however, there is lack of clinical research on the effects of propolis.Strategy and objectives: Since propolis-containing products have been marketed and humans have used propolis for different purposes, the goal of this review is to discuss the potential of propolis for the development of new drugs, by comparing data from the literature that suggest candidate areas for the establishment of drugs against tumors, infections, allergy, diabetes, ulcers and with immunomodulatory action.Conclusions: The efficacy of propolis in different protocols in vitro and in vivo suggests its therapeutic properties, but before establishing a strategy using this bee product, it is necessary to study: (a) the chemical nature of the propolis sample. (b) Propolis efficacy should be compared to well-established parameters, e.g. positive or negative controls in the experiments. Moreover, possible interactions between propolis and other medicines should be investigated in humans as well. (c) Clinical investigation is needed to evaluate propolis potential in patients or healthy individuals, to understand under which conditions propolis may promote health. Data point out the importance of this research field not only for the readers and researchers in the scientific community waiting for further clarification on the potential of propolis but also for the pharmaceutical industry that looks for new drugs. (C) 2010 Elsevier B.V. All rights reserved.

Acerola: importance, culture conditions, production and biochemical aspects

Origin and importance. Acerola, or Malpighia emarginata D. C., is native to the Caribbean islands, Central America and the Amazonian region. More recently, it has been introduced in subtropical areas (Asia, India and South America). The vitamin C produced by acerola is better absorbed by the human organism than synthetic ascorbic acid. Exportation of acerola crops is a potential alternative source of income in agricultural businesses. In Brazil, the commercial farming of acerola is quite recent. Climatic conditions. Acerola is a rustic plant. It can resist temperatures close to 0 degrees C, but it is well adapted to temperatures around 26 degrees C with rainfall between (1200 and 1600) mm per year. Fruit characteristics. Acerola fruit is drupaceous, whose form can vary from round to conic. When ripe, it can be red, purple or yellow. The fruit weight varies between (3 and 16) g. Maturation. Acerola fruit presents fast metabolic activity and its maturation occurs rapidly. When commercialised in ambient conditions, it requires fast transportation or the use of refrigerated containers to retard its respiration and metabolism partially. Production and productivity. Flowering and fruiting are typically in cycles associated with rain. Usually, they take place in 25-day cycles, up to 8 times per year. The plant can be propagated by cuttings, grafting or seedlings. Harvest. Fruits produced for markets needs to be harvested at its optimal maturation stage. For distant markets, they need to be packed in boxes and piled up in low layers; transportation should be done in refrigerated trucks in relatively high humid conditions. Biochemical constituents. Acerola is the most important natural source of vitamin C [(1000 to 4500) mg.100(-1) g of pulp], but it is also rich in pectin and pectolytic enzymes, carotenoids, plant fibre, vitamin B, thiamin, riboflavin, niacin, proteins and mineral salts. It has also shown active anti-fungal properties. Products and market. Acerola is used in the production of juice, soft drinks, gums and liqueurs. The USA and Europe are great potential markets. In Europe, acerola extracts are used to enrich pear or apple juices. In the USA, they are used in the pharmaceutical industry. Conclusions. The demand for acerola has increased significantly in recent years because of the relevance of vitamin C in human health, coupled with the use of ascorbic acid as an antioxidant in food and feed. Acerola fruit contains other significant components, which are likely to lead to a further increase in its production and trade all over the world.

Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline

In early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema, only (-)-spectaline exhibited an anti-inflammatory profile, showing an ED(50) value of 56.6 mu mol/kg. Our results suggest different mechanisms of action for the analgesic activity observed for LASSBio-776 (3-O-Bocspectaline), LASSBio-755 (3-O-acetyl-spectaline) and (-)-spectaline (LASSBio-754). The antinociceptive profile of some of the semi-synthetic spectaline derivatives extends our research concerning the chemical and pharmacological optimization of isolated natural products in the search of new drug candidates from brazilian biodiversity.

Planejamento racional de fármacos baseado em produtos naturais

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development of a bioassay to quantify the ricin toxin content of castor bean (Ricinus communis L.) seeds

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Morfoanatomia e histoquímica de Brosimum gaudichaudii Trécul (Moraceae)

Brosimum gaudichaudii, conhecida como mamacadela, é espécie comum nos cerrados, com grande valor na medicina popular e na indústria de medicamentos. A casca da raiz e do caule é empregada no tratamento do vitiligo, sendo o bergapteno e psoraleno, duas furanocumarinas, responsáveis pela ação farmacológica. Neste trabalho são apresentadas a caracterização morfoanatômica e a histoquímica de órgãos vegetativos de B. gaudichaudii, com informações sobre o embrião e o desenvolvimento pós-seminal. Amostras foram processadas segundo técnicas usuais em anatomia e ultra-estrutura vegetal. O embrião é do tipo total e invaginado, a plântula cripto-hipogéia e o sistema radicular do tirodendro é composto por raiz primária pouco desenvolvida em relação às raízes laterais. Plantas adultas apresentam raízes gemíferas longas, plagiotrópicas originando ramos caulinares aéreos; tais raízes possuem periderme com súber desenvolvido e floema secundário abundante em relação ao xilema, sendo facilmente destacados quando manipulados. O caule jovem e a folha apresentam epiderme unisseriada, grande densidade de tricomas tectores unicelulares e tricomas glandulares. Laticíferos não-articulados ramificados ocorrem em todos os órgãos, podendo invadir os elementos de vaso. Idioblastos fenólicos ocorrem em abundância em todos tecidos e órgãos analisados. O valor das características anatômicas observadas no controle de qualidade da droga é discutido.

Lições para a história das ciências no Brasil: Instituto Pasteur de São Paulo

Este artigo pretende mostrar a importância e o papel do Instituto Pasteur de São Paulo (1903-16) no desenvolvimento da ciência microbiológica no Brasil e no surgimento da indústria farmacêutica de capital nacional.

Saúde pública e as empresas químico-farmacêuticas

O artigo trata da formação da indústria farmacêutica brasileira. Aborda algumas questões de história econômica e social, tais como o surgimento do sistema de saúde pública, as práticas de combate às doenças infecciosas, desde as desinfecções e produção de substâncias químicas pela indústria, à soroterapia e produção de soros e vacinas nas instituições de pesquisa científica públicas e nas empresas farmacêuticas privadas. Toma para análise da indústria farmacêutica privada nacional, a empresa Instituto Pinheiros - Produtos Terapêuticos S.A., enfatizando as relações entre seus cientistas, no desenvolvimento de produtos, de tecnologia e da própria discussão científica com as instituições públicas de pesquisa criadas no âmbito da política de saúde pública pelo estado de São Paulo.

Gastric antiulcer activity of Syngonanthus arthrotrichus SILVEIRA

Syngonanthus arthrotrichus SILVEIRA, popularly known as sempre-vivas mini-saia, is found in mountains of the Espinhaco range in the Brazilian states of Bahia and Minas Gerais. Extracts of this species contain several constituents, including flavonoids which may have antiulcerogenic activity. An ethanolic extract (EEOH), and flavonoid-rich (FRF) and flavonoid-deficient (FDF) fractions obtained from the scapes of S. arthrotrichus were investigated for their ability to prevent ulceration of the gastric mucosa in mice and rats. In the ethanol/HCl-induced ulcer model, lansoprazole (30 mg/kg), EEOH (50, 100, 250 mg/kg) given orally protected the gastric mucosal against injury in mice by 79%, 78%, 73%, and 64% respectively. In the ethanol-induced gastric ulcer model in rats, the lansoprazole (30 mg/kg), FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of rats by 65%, 38% and 25% respectively when compared with the negative control group. In indomethacin/ bethanechol-induced gastric ulcers, cimetidine (100 mg/kg) and the EEOH (100, 250 mg/kg) inhibited gastric ulcer formation by 73%, 55% and 32% respectively. In this exactly model other treatments as cimetidine, FRF and FDF (100 mg/kg) each caused 54%, 36% and 45% inhibition, respectively. In the stress-induced gastric ulcer model, cimetidine (100 mg/kg) and the EEOH (50, 100, 250 mg/kg), inhibited gastric ulcer formation by 63%, 73%, 68% and 69% respectively. In the same model, cimetidine, FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of the mice by 60%, 51% and 47% when compared to the control group. In pylorus-ligated mice, cimetidine (positive control) and FRF significantly decreased gastric acid secretion, increased gastric pH and reduced the acid output when compared to the negative control. FDF had no significant effect on these parameters. The protection provided by FRF probably involved an antisecretory mechanism mediated by flavonoids which were absent in FDF. The amount of adherent mucous in the stomach contents was also evaluated with the treatments carbenoxolone (200 mg/kg), FRF and FDF (100 mg/kg) treatment. Each treatments significantly increased the amount of adherent mucous in the gastric juice (8.67 +/- 1.73, 3.35 +/- 1.59, 2.1 +/- 0.41 mg/g of wet tissue, respectively) compared to the control group, indicating a cytoprotective action on the gastric mucosa. Treatment with FRF plus indomethacin and FDF plus indomethacin reduced the prostaglandin biosyntesis (13.6 +/- 6.5, 27 +/- 5.5 pg/well) by the mucosa, indicating that the cytoprotective action on the gastric mucosa was not related to the level of prostaglandins. Only FDF (38 +/- 17 pg/well) maintained the level of prostaglandins and guaranteed the integrity of the mucosa. The results indicate that the EEOH, FRF and FDF have antisecretory and cytoprotective actions, that may be related to the presence of luteoline in the extract and active fractions.