Topical Delivery of Lycopene Using Microemulsions: Enhanced Skin Penetration and Tissue Antioxidant Activity

Topical delivery of lycopene is a convenient way to supplement cutaneous levels of antioxidants. In this study, lycopene was incorporated (0.05%, w/w) in two microemulsions containing BRIJ-propylene glycol (2:1, w/w, surfactant blend) but different oil phases: mono/diglycerides of capric and caprylic acids (MG) or triglycerides of the same fatty acids (TG). Microemulsions containing MG and TG were isotropic, fluid, and clear, with internal phase diameters of 27 and 52 nm, respectively. Both MG- or TG-containing microemulsions markedly increased lycopene penetration in the stratum corneum, (6- and 3.6-fold, respectively) and in viable layers of porcine ear skin 2 (from undetected to 172.6 +/- 41.1 and 103.1 +/- 7.2 ng/cm(2), respectively) compared to a control solution. To assure that lycopene delivered to the skin was active, the antioxidant activity of skin treated with MG-containing microemulsion was determined by CUPRAC assay, and found to be 10-fold higher than untreated skin. The cytotoxicity of MG-containing microemulsion in cultured fibroblasts was similar to propylene glycol (considered safe) and significantly less than of sodium lauryl sulfate (a moderate-to-severe irritant) at 1-50 mu g/mL. These results demonstrate that the MG-containing microemulsion is an efficient and safe system to increase lycopene delivery to the skin and the antioxidant activity in the tissue. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1346-1357, 2010

Schistosomicidal and trypanocidal structure-activity relationships for (+/-)-licarin A and its (-)- and (+)-enantiomers

(+/-)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (-)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC(50) value of 53.57 mu M and moderate trypanocidal activity with an IC(50) value of 127.17 mu M. On the other hand, the (-)-enantiomer (2), displaying a LC(50) value of 91.71 mu M, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC(50) of 23.46 mu M) than enantiomer 3, which showed an IC(50) value of 87.73 mu M. Therefore, these results suggest that (+/-)-licarin A (1) and (-)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents. (C) 2011 Elsevier Ltd. All rights reserved.

In vitro cytotoxic activity of Baccharis dracunculifolia and propolis against HEp-2 cells

Baccharis dracunculifolia is the most important vegetal source of propolis in southeast Brazil, and researchers have been investigating its biological properties. Propolis is a complex resinous hive product collected by bees from several plants, showing a very complex chemical composition. It has been employed since ancient times due to its therapeutic properties, such as antimicrobial, anti-inflammatory, antioxidant, immunomodulatory and antitumour activities, among others. The goal of this work was to compare the cytotoxic action of B. dracunculifolia, propolis and two isolated compounds (caffeic and cinnamic acids) on human laryngeal epidermoid carcinoma (HEp-2) cells in vitro. These cells were incubated with different concentrations of each variable, and cell viability was assessed by the crystal violet method. Lower concentrations of B. dracunculifolia (extract and essential oil), propolis, as well as caffeic and cinnamic acids, showed no cytotoxic activity against HEp-2 cells. On the other hand, elevated concentrations (50 and 100 mu g per 100 mu L) exerted a cytotoxic action, and propolis showed a more efficient action than its vegetal source and isolated compounds. Further investigation is still needed in order to explore the potential of these variables as antitumour agents and to understand their mechanisms of action.

Trypanosoma cruzi: evaluation of (-)-cubebin derivatives activity in the messenger RNAs processing

No fully effective treatment has been developed since the discovery of Chagas` disease. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effective in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing, which is unusual RNA processing reaction, and it implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. Cubebin derivatives seem to provide treatments with less collateral effects than benznidazole and showed similar or better trypanocidal activities than benznidazole. Therefore, the cubebin derivatives ((-)-6,6`-dinitrohinokinin (DNH) and (-)-hinokinin (HQ)) interference in the mRNA processing was evaluated using T. cruzi permeable cells (Y and BOL (Bolivia) strains) following by RNase protection reaction. These substances seem to intervene in any step of the RNA transcription, promoting alterations in the RNA synthesis, even though the RNA processing mechanism still occurs. Furthermore, HQ presented better activity against the parasites than DNH, meaning that BOL strain seems to be more resistant than Y.

Antiulcerogenic Activity of the Essential Oil of Baccharis dracunculifolia on Different Experimental Models in Rats

Baccharis dracunculifolia DC (Asteraceae), a native plant from Brazil, commonly known as `Alecrim-do-campo` is widely used in folk medicine to treat inflammation, hepatic disorders and stomach ulcers, and it is the most important botanical source of Southeastern Brazilian propolis, known as green propolis. Its essential oil is composed of non-oxygenated and oxygenated terpenes. In this work, the effects of the essential oil obtained from the aerial parts of R dracunculifolia on gastric ulcers were evaluated. The antiulcer assays were undertaken using the following protocols in rats: nonsteroidal antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, stress-induced ulcer, and determination of gastric secretion using ligated pylorus. The treatment in the doses of 50, 250 and 500 mg/kg of R dracunculifolia essential oil significantly diminished the lesion index, the total lesion area and the percentage of lesions in comparison with both positive and negative control groups. With regard to the model of gastric secretion a reduction of gastric juice volume and total acidity was observed, as well as an increase in the gastric pH. No sign of toxicity was observed in the acute toxicity study. Considering the results, it is suggested that the essential oil of B. dracunculifolia could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer. Copyright (C) 2009 John Wiley & Sons, Ltd.

Antimicrobial activity of crude extratcs of Petiveria alliacea L.

Antimicrobial activity of crude extratcs of Petiveria alliacea L.. Petiveria alliacea L. (Phytolaccacea) is an herbaceous plant of great importance in traditional medicine. This species have been widely used in several applications such as antirheumatic, anticarcinogenic, anti-flu, antitussive, analgesic, insecticidal, acaricidal, as well as bactericide and fungicide. Currently, the pathogenic microorganisms are acquiring resistence against the traditional antibiotics, and the search for new herbal antimicrobial agents has been intensified. The objective of this study was to evaluate the antifungal and antibacterial activity of several leaf crude extracts of P. alliacea against several strains of bacterias and yeasts namely Bacilus subtilis, Pseudomonas aeruginosa, Escherichia coli, Streptococcus mutans, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Candida parapsilosis, Candida kefyr and Candida albicans, using microdilution method. Promising results were observed for the 70% v/v ethanolic extract which presented minimum inhibitory concentration (MIC) from 250 to 760 mu g/mL for yeast. For the bacteria strains tested the MIC ranged between 240 to 3960 mu g/mL, depending of the extractive solution tested.

Sub-Chronic Exposure to Methylmercury at Low Levels Decreases Butyrylcholinesterase Activity in Rats

In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 mu g/kg/day) by gavage; (Group III) received MeHg (100 mu g/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

Comparison of oxidation efficiency of disperse dyes by chemical and photoelectrocatalytic chlorination and removal of mutagenic activity

Degradation of Disperse Orange 1, Disperse Red 1 and Disperse Red 13 dyes has been performed using electrochemical oxidation on Pt electrode, chemical chlorination and photoelectrochemical oxidation on Ti/TiO(2) thin film electrodes in NaCl or Na(2)SO(4) medium. 100% discoloration was obtained for all tested methods after 1 h of treatment. Faster color removal was obtained by photoelectrocatalytic oxidation in 0.1 mol L(-1) NaCl pH 4.0 under UV light and an applied potential of +1.0V (vs SCE reference electrode), which indicates also values around 60% of TOC removal. The conventional chlorination method and electrochemical oxidation on Pt electrode resulted in negligible reduction of TOC removal. All dyes showed positive mutagenic activity in the Salmonella/microsome assay with the strain TA98 in the absence and presence of S9 (exogenous metabolic activation). Nevertheless, there is complete reduction of the mutagenic activity after 1 h of photoelectrocatalytic oxidation, suggesting that this process would be good option to remove disperse azo dyes from aqueous media. (C) 2008 Elsevier Ltd. All rights reserved.

Candida albicans and Candida tropicalis in Oral Candidosis: Quantitative Analysis, Exoenzyme Activity, and Antifungal Drug Sensitivity

Candida albicans and C. tropicalis obtained from whole saliva of patients presenting signs of oral candidosis were assayed for quantification of colony forming units, exoenzyme activity (phospholipase and proteinase) and antifungal drug sensitivity (amphotericin B, fluconazole and itraconazole) by the reference method of the Clinical and Laboratory Standards Institute. The number of colony forming units per milliliter varied according to the Candida species involved and whether a single or mixed infection was present. Proteinase activity was observed in both C. albicans and C. tropicalis, but phospholipase activity was noted only in C. albicans. In vitro resistance to antifungals was verified in both species, but C. tropicalis appears to be more resistant to the tested antifungals than C. albicans.

Trypanocidal Activity of Limonoids and Triterpenes from Cedrela fissilis

Chagas` disease is an illness that affects millions of people in Central and South America, The search for both a prophylactic drug to be added to human blood as well as a safe and reliable therapeutic drug are greatly needed to control such disease. Herein, we report the trypanocidal activity of 15 crude extracts and 14 Compounds (limonoids and triterpenes) as well as the isolation of 25 known compounds (6 limonoids, 12 triterpenes, 1 sesquiterpene, 5 steroids, and 1 flavonoid) from Cedrela fissilis. The present study shows that this plant is a Promising Source of active compounds for the control of Chagas` disease. The inhibitory activity found for odoratol indicates that it is potentially useful as an alternative for the chemoprophylactic gentian violet.

Antineurotoxic activity of Galactia glaucescens against Crotalus durissus terrificus venom

Ethanolic extract of leaves of Galactia glauscescens (GGE) at concentration of 100 and 500 mu g/ml prevented the neuromuscular paralysis induced by Crotalus durissus terrificus venom on mouse phrenic nerve-diaphragm preparation. (C) 2008 Elsevier B.V. All rights reserved.

Enzymatic inhibitory activity and trypanocidal effects of extracts and compounds from Siphoneugena densiflora O. Berg and Vitex polygama Cham.

Hexanic, methanolic, and hydroalcoholic extracts, and 34 isolated compounds from Vitex polygama Cham. (Lamiaceae, formely Verbenaceae) and Siphoneugena densiflora O. Berg (Myrtaceae) were screened for their trypanocidal effects on bloodstream forms of Trypanosoma cruzi and T brucei, as well as for their enzymatic inhibitory activities on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) and trypanothione reductase (TR) enzymes from T cruzi and adeninephosphoribosyl transferase (APRT) enzyme from Leishmania tarentolae. In general, polar extracts displayed strong effects and some of the tested compounds have shown good results in comparison to positive controls of the bioassays.

Molecular characterization of BjussuSP-I, a new thrombin-like enzyme with procoagulant and kallikrein-like activity isolated from Bothrops jararacussu snake venom

A thrombin-like enzyme, named BjussuSP-I, isolated from Bothrops jararacussu snake venom, is an acidic single-chain glycoprotein with M-r = 61,000, pI similar to 3.8 and 6% sugar. BjussuSP-I shows high proteolytic activity upon synthetic substrates, such as S-2238 and S-2288. It also shows procoagulant and kallikrein-like activity, but is unable to act on platelets and plasmin. These activities are inhibited by specific inhibitors of this class of enzymes. The complete cDNA sequence of BjussuSP-I with 696 bp encodes open reading frames of 232 amino acid residues, which conserve the common domains of thrombin-like serine proteases. BjussuSP-I shows a high structural homology with other thrombin-like enzymes from snake venoms where common amino acid residues are identified as those corresponding to the catalytic site and subsites S1, S2 and S3 already reported. In this study, we also demonstrated the importance of N-linked glycans, to improve thrombin-like activity of BjussuSP-I toxin. (c) 2007 Elsevier Masson SAS. All rights reserved.

Trypanocidal activity of quinonemethide triterpenoids from Cheiloclinium cognatum (Hippocrateaceae)

We report the trypanocidal activity of quinonemethide triterpenoids isolated from root extracts of Cheiloclinium cognatum, a plant of the Hippocrateaceae family, collected in the Cerrado Reserve at Universidade Federal de Goias, Brazil. The trypanocidal activity assays showed an effect on the blood trypomastigote forms of the Y strain of Trypanosoma cruzi where tingenone and tingenol demonstrated activity on the parasite. Their structures were elucidated on the basis of spectral data, particularly COSY, HMQC and HMBC experiments, and chemical transformations.

The Ruthenium Complex cis-(Dichloro) Tetraammineruthenium(III) Chloride Presents Immune Stimulatory Activity on Human Peripheral Blood Mononuclear Cells

Ruthenium compounds in general are well suited for medicinal applications. They have been investigated as immunosuppressants, nitric oxide scavengers, antimicrobial agents, and antimalarials. The aim of this study is to evaluate the immunomodulatory activity of cis-(dichloro) tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) on human peripheral blood mononuclear cells (PBMC). The cytotoxic studies performed here revealed that the ruthenium( III) complex presents a cytotoxic activity towards normal human PBMC, only at very high concentration. Results also showed that cis-[ RuCl(2)(NH(3))(4)] Cl presents a dual role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low concentration and inducing cytotoxicity, inability to proliferate, and inhibiting IL-2 production at high concentration. The noncytotoxic activity of cis-[RuCl(2)(NH(3))(4)] Cl at low concentration towards PBMC, which correlates with the small number of annexin V positive cells and also the absence of DNA fragmentation, suggest that this compound does not induce apoptosis on PBMC. For the first time, we show that, at low concentration (10-100 mu g L(-1)), the cis-[ RuCl(2)(NH(3))(4)] Cl compound induces peripheral blood lymphocytes proliferation and also stimulates them to IL-2 production. These results open a new potential applicability of ruthenium(III) complexes as a possible immune regulatory compound acting as immune suppressor at high concentration and as immune stimulator at low concentration.