In vivo activity of Sapindus saponaria against azole-susceptible and -resistant human vaginal Candida species

<p>Abstract</p> <p>Background</p> <p>Study of <it>in vivo </it>antifungal activity of the hydroalcoholic extract (HE) and n-BuOH extract (BUTE) of <it>Sapindus saponaria </it>against azole-susceptible and -resistant human vaginal <it>Candida </it>spp.</p> <p>Methods</p> <p>The <it>in vitro </it>antifungal activity of HE, BUTE, fluconazole (FLU), and itraconazole (ITRA) was determined by the broth microdilution method. We obtained values of minimal inhibitory concentration (MIC) and minimum fungicide concentration (MFC) for 46 strains of <it>C. albicans </it>and 10 of <it>C. glabrata </it>isolated from patients with vulvovaginal candidiasis (VVC). VVC was induced in hyperestrogenic Wistar rats with azole-susceptible <it>C. albicans </it>(SCA), azole-resistant <it>C. albicans </it>(RCA), and azole-resistant <it>C. glabrata </it>(RCG). The rats were treated intravaginally with 0.1 mL of HE or BUTE at concentrations of 1%, 2.5% and 5%; 100 μg/mL of FLU (treatment positive control); or distilled water (negative control) at 1, 24, and 48 h after induction of the infection, and the progress of VVC was monitored by culturing and scanning electron microscopy (SEM). The toxicity was evaluated in cervical cells of the HeLa cell line.</p> <p>Results</p> <p>The extracts showed <it>in vitro </it>inhibitory and fungicidal activity against all the isolates, and the MIC and MFC values for the <it>C. glabrata </it>isolates were slightly higher. <it>In vivo</it>, the SCA, RCA, and RCG infections were eliminated by 21 days post-infection, with up to 5% HE and BUTE, comparable to the activity of FLU. No cytotoxic action was observed for either extract.</p> <p>Conclusions</p> <p>Our results demonstrated that HE and BUTE from <it>S. saponaria </it>show inhibitory and fungicidal activity <it>in vitro</it>, in addition to <it>in vivo </it>activity against azole-resistant vaginal isolates of <it>C. glabrata </it>and azole-susceptible and resistant isolates of <it>C. albicans</it>. Also considering the lack of cytotoxicity and the low concentrations of the extracts necessary to eliminate the infection <it>in vivo</it>, HE and BUTE show promise for continued studies with purified antifungal substances in VVC yeast isolates.</p

Cytochrome P450-derived eicosanoids: the neglected pathway in cancer

Endogenously produced lipid autacoids are locally acting small molecule mediators that play a central role in the regulation of inflammation and tissue homeostasis. A well-studied group of autacoids are the products of arachidonic acid metabolism, among which the prostaglandins and leukotrienes are the best known. They are generated by two pathways controlled by the enzyme systems cyclooxygenase and lipoxygenase, respectively. However, arachidonic acid is also substrate for a third enzymatic pathway, the cytochrome P450 (CYP) system. This third eicosanoid pathway consists of two main branches: ω-hydroxylases convert arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) and epoxygenases convert it to epoxyeicosatrienoic acids (EETs). This third CYP pathway was originally studied in conjunction with inflammatory and cardiovascular disease. Arachidonic acid and its metabolites have recently stimulated great interest in cancer biology; but, unlike prostaglandins and leukotrienes the link between cytochome P450 metabolites and cancer has received little attention. In this review, the emerging role in cancer of cytochrome P450 metabolites, notably 20-HETE and EETs, are discussed

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Biological activity and isolated compounds in Sapindus saponaria L. and other plants of the genus Sapindus

Species of Sapindus (Sapindaceae) are widespread throughout the tropics (e.g., Brazil, China and India). The present report is based on available data and references on species of this genus. The main substances found in plants of the genus Sapindus are acetylated triterpenic saponin and acyclic sesquiterpene oligoglycosides. These plants have antimicrobial, spermicidal, antiulcer, hepatoprotective, molluscicidal, fungicidal and anti-inflammatory activity. In Brazil, the fruit of Sapindus saponaria L. is employed in folk medicine in the treatment of ulcers and external wounds.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Antifungal activity of the extracts and saponins from Sapindus saponaria L.

Extracts from the dried pericarp of Sapindus saponaria L. (Sapindaceae) fruits were investigated for their antifungal activity against clinical isolates of yeasts Candida albicans and C. non-albicans from vaginal secretions of women with Vulvovaginal Candidiasis. Four clinical isolates of C. albicans, a single clinical isolated of each of the species C. parapsilosis, C. glabrata, C. tropicalis, and the strain of C. albicans ATCC 90028 were used. The hydroalcoholic extract was bioactivity-directed against a clinical isolate of C. parapsilosis, and showed strong activity. The n-BuOH extract and one fraction showed strong activity against all isolates tested. Further column-chromatography on silica gel separation of this fraction afforded two pure triterpene acetylated saponins: 3-O-(4-acetyl-beta-D-xylopyranosyl)-(1->3)-alpha-Lrhamnopyranosyl-(1->2)-alpha-L-arabinopyranosyl-hederagenin (1) and 3-O-(3,4-di-acetyl-beta-D-xylopyranosyl)-(1->3)-alpha-L-rhamnopyranosyl-(1->2)-alpha-L-arabynopyranosyl-hederagenin (2). The structures of the compounds were based on spectral data (¹H and 13C NMR, HSQC, HMBC and MS), and on with literature. The saponins isolated showed strong activity against C. parapsilosis.Extratos do pericarpo de frutos de Sapindus saponaria L. (Sapindaceae) foram testados para a atividade antifúngica sobre isolados clínicos de leveduras de Candida albicans e C. não-albicans obtidos de secreção vaginal de mulheres com Candidíase Vulvovaginal. Foram avaliados quatro isolados clínicos de C. albicans, um de cada uma das espécies C. glabrata, C. parapsilosis, C. tropicalis e uma cepa referência de C. albicans ATCC 90028. O extrato hidroalcoólico foi biomonitorado contra um isolado clínico de C. parapsilosis, apresentando forte atividade. O extrato butanólico e uma fração apresentaram forte atividade contra todos os isolados testados. Posterior análise desta fração via cromatografia em sílica gel (CHCl3:CH3OH, 1:1, v/v) resultou no isolamento de duas saponinas triterpênicas puras mono e diacetiladas, 3-O-(4-O-acetil-O-beta-D-xilopiranosil)-(1 -> 3)-alfa-L-ramnopiranosil-(1 -> 2)-alfa-L-arabinopiranosil-hederagenina (1) e 3-O-(3,4-di-O-acetil-beta-D-xilopiranosil)-(1 -> 3)-alfa-L-ramnopiranosil-(1 -> 2)-alfa-L-rabinopiranosil-hederagenina (2) respectivamente. A elucidação estrutural das substâncias foi baseada em dados espectrais (RMN de ¹H e de 13C, HSQC, HMBC, ESI/MS) e comparados com dados da literatura. As saponinas triterpênicas isoladas (1) e (2) apresentaram forte atividade contra C. parapsilosis

Pre-clinical (acute and sub-acute) toxicologic study of phytomedicinal Propovit Plus® in rodents

Realizou-se a avaliação toxicológica do fitoterápico Propovit Plus® em roedores. Os testes agudos não produziram mortalidade, com DL50 acima de 5 g/kg (oral) e 2,5 g/kg (i.p.), mas encontrou-se diminuição no peso dos corações dos grupos 5 g/kg (oral) e 2,5; 1,5 e 1,0 g/kg (i.p.). No tratamento sub-agudo, ocorreram três mortes no grupo 1,5 g/kg, aumento no peso dos pulmões dos machos tratados com a dose de 1,5 g/kg, aumento no peso do fígado e diminuição no peso dos pulmões das fêmeas tratadas também com a maior dose. Os testes sangüíneos mostraram diversos resultados significativos, embora sem correlação dose-resposta, sem ocorrência em ambos os sexos e com vários parâmetros dentro de faixas de normalidade. A avaliação histopatológica evidenciou poucas alterações, ocorrentes em praticamente todos os grupos e não dependentes da dose. Demonstra-se que o produto Propovit Plus® apresenta baixa toxicidade, mais evidente na dose de 1,5 g/kg, cerca de sessenta vezes maior que a dose terapêutica.We report the toxicological evaluation of the phytomedicinal Propovit Plus in rodents. The acute tests didn't produce mortality, with DL50 above 5 g/kg (oral) and 2,5 g/kg (i.p.), but it was decrease in the weight of the hearts in groups 5 g/kg (oral) and 2,5; 1,5 and 1,0 g/kg (i.p.). In the long-term treatment, it happened three deaths in the group 1,5 g/kg, increase in the weight of the lungs of the males treated with the dose of 1,5 g/kg, increase in the weight of the liver and decrease in the weight of the lungs of the females also treated with the largest dose. The blood tests showed several significant results, although without correlation dose-answer, occurrence in both sexes and with several parameters inside of normality strips. The histological evaluation evidenced few alterations in practically all of the groups and was no dose-dependent. It is demonstrated that the product Propovit Plus present low toxicity, more evident in the dosage of 1,5 g/kg, about sixty times larger than the therapeutic dosage.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Pre-clinical (acute and sub-acute) toxicologic study of phytomedicinal Propovit Plus® in rodents

Realizou-se a avaliação toxicológica do fitoterápico Propovit Plus® em roedores. Os testes agudos não produziram mortalidade, com DL50 acima de 5 g/kg (oral) e 2,5 g/kg (i.p.), mas encontrou-se diminuição no peso dos corações dos grupos 5 g/kg (oral) e 2,5; 1,5 e 1,0 g/kg (i.p.). No tratamento sub-agudo, ocorreram três mortes no grupo 1,5 g/kg, aumento no peso dos pulmões dos machos tratados com a dose de 1,5 g/kg, aumento no peso do fígado e diminuição no peso dos pulmões das fêmeas tratadas também com a maior dose. Os testes sangüíneos mostraram diversos resultados significativos, embora sem correlação dose-resposta, sem ocorrência em ambos os sexos e com vários parâmetros dentro de faixas de normalidade. A avaliação histopatológica evidenciou poucas alterações, ocorrentes em praticamente todos os grupos e não dependentes da dose. Demonstra-se que o produto Propovit Plus® apresenta baixa toxicidade, mais evidente na dose de 1,5 g/kg, cerca de sessenta vezes maior que a dose terapêutica.We report the toxicological evaluation of the phytomedicinal Propovit Plus in rodents. The acute tests didn't produce mortality, with DL50 above 5 g/kg (oral) and 2,5 g/kg (i.p.), but it was decrease in the weight of the hearts in groups 5 g/kg (oral) and 2,5; 1,5 and 1,0 g/kg (i.p.). In the long-term treatment, it happened three deaths in the group 1,5 g/kg, increase in the weight of the lungs of the males treated with the dose of 1,5 g/kg, increase in the weight of the liver and decrease in the weight of the lungs of the females also treated with the largest dose. The blood tests showed several significant results, although without correlation dose-answer, occurrence in both sexes and with several parameters inside of normality strips. The histological evaluation evidenced few alterations in practically all of the groups and was no dose-dependent. It is demonstrated that the product Propovit Plus present low toxicity, more evident in the dosage of 1,5 g/kg, about sixty times larger than the therapeutic dosage.Colegio de Farmacéuticos de la Provincia de Buenos Aire