The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

A proposal for chemical characterization and quality evaluation of botanical raw materials using glandular trichome microsampling of yacón (Polymnia sonchifolia, Asteraceae), an Andean medicinal plant

A proposal for chemical characterisation and quality evaluation of botanical raw materials by analysing the glandular trichomes from the leaves of two different populations of yacón (Polymnia sonchifolia Poeppig & Endlicher, Asteraceae) is described. This species is an Andean medicinal plant and the tea prepared with their leaves displays hypoglycemic property. The method was based on the glandular trichome microsampling using LC/DAD. Qualitative chromatographic fingerprints of the glands were obtained by isocratic runs and then compared between the two populations, showing the same qualitative profile. The two main metabolites detected in the glands were later isolated from a leaf rinse extract by preparative separation and identified as the melampolides enhydrin and uvedalin. These compounds, subtypes of sesquiterpene lactones, were used as chemical markers. This technique is applicable to other medicinal plants and can be used for the evaluation of the quality of dried material or leaf rinse extracts.

Neste trabalho é descrita uma proposta para a caracterização química e avaliação da qualidade de drogas vegetais através da análise de tricomas glandulares das folhas de duas populações diferentes de yacón (Polymnia sonchifolia Poeppig & Endlicher, Asteraceae). Esta espécie é uma planta medicinal andina e o chá preparado com suas folhas apresenta propriedade hipoglicemiante. O método baseou-se na microamostragem de tricomas glandulares, empregando-se cromatografia líquida de alta eficiência e detecção por arranjo de diodos. As impressões digitais dos cromatogramas das glândulas foram obtidas em sistema isocrático e comparadas entre si, resultado em um mesmo perfil qualitativo para ambas as populações avaliadas. Os dois metabólitos principais encontrados nas glândulas foram isolados através de métodos preparativos a partir de um extrato de lavagem foliar, sendo identificados como enidrina e uvedalina. Estas substâncias, subtipos de lactonas sesquiterpênicas, foram utilizadas como marcadores químicos. Esta técnica é aplicável a outras plantas medicinais e pode ser usada para avaliar a qualidade de materiais secos ou extratos foliares.

Immune and hormonal activity in adults suffering from depression

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5 percent) were females and 11 (27.5 percent) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation

Neonatal treatment with naloxone causes permanent hyperalgesia in rats

The effect of treatment with naloxone early in life on pain responsiveness was studied in Wistar rats. Litters of six rats were divided equally into groups of 3 pups receiving daily naloxone (50 mg/kg, sc) and 3 pups receiving saline from the 3rd to 18th day of life. On days 30, 50, 70 and 90, one group of animals previously injected during suckling with naloxone (N = 21) and another with saline (N = 21) were submitted to the hot-plate test to measure the latency to paw licking. Other groups of rats also treated during suckling with naloxone (N = 13) and saline (N = 14) were assessed for the antinociceptive effect of morphine (10 mg/kg,sc). The naloxone group displayed a lower latency than the saline group in all test sessions and a diminished analgesic response to morphine. The results indicate that the use of naloxone (an antagonist opioid) during suckling, the brain growth spurt period, facilitates a long-lasting increased pain responsiveness and alters antialgesic mechanisms. In this respect, the opioid and non-opioid effects of naloxone on the ontogeny of neural systems should be taken into account