Effect of Brazilian green propolis in chronic ulcer treatment: a randomized clinical trial.

OBJECTIVE: to assess the effectiveness of 5% Brazilian green propolis (ointment) in individuals with chronic ulcers. METHODS: a randomized clinical trial, developed with 40 patients randomized equally to control group (treated with essential fatty acid) and experimental group (treated with 5% green propolis) for 30 days. The outcomes of interest were sociodemographic, clinical and laboratory characteristics, lesion characteristics, such as type of tissue in the bed, presence of exudate, edge characteristics, microbial content and pain. RESULTS: regarding sociodemographic, clinical and laboratory characteristics, the two groups did not show statistically significant differences. After assessment in 30 days, an effect was observed for both treated groups, but for the experimental group, greater effectiveness in terms of the type of tissue in the bed, type of exudate, edge characteristics, microbial content and pain. CONCLUSION: propolis-based ointment showed a healing effect, presenting itself as a potential tool in healing chronic ulcers.

Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

INTRODUCTION: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. OBJECTIVE: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. METHODS: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-ß, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student's t-test. RESULTS: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-ß transcripts were less expressed in the UT-treated. CONCLUSION: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.

Effect of Brazilian green propolis in chronic ulcer treatment: a randomized clinical trial / Efecto delpropóleo verde brasileño en el tratamiento de úlceras crónicas: ensayo clínico aleatorizado / Efeito da própolis verde brasileira no tratamento de úlceras crônicas: ensaio clínico randomizado

ABSTRACT Objective: to assess the effectiveness of 5% Brazilian green propolis (ointment) in individuals with chronic ulcers. Methods: a randomized clinical trial, developed with 40 patients randomized equally to control group (treated with essential fatty acid) and experimental group (treated with 5% green propolis) for 30 days. The outcomes of interest were sociodemographic, clinical and laboratory characteristics, lesion characteristics, such as type of tissue in the bed, presence of exudate, edge characteristics, microbial content and pain. Results: regarding sociodemographic, clinical and laboratory characteristics, the two groups did not show statistically significant differences. After assessment in 30 days, an effect was observed for both treated groups, but for the experimental group, greater effectiveness in terms of the type of tissue in the bed, type of exudate, edge characteristics, microbial content and pain. Conclusion: propolis-based ointment showed a healing effect, presenting itself as a potential tool in healing chronic ulcers.

RESUMEN Objetivo: evaluar la eficacia del propóleo (ungüento) verde brasileño al 5% en personas con úlceras crónicas. Métodos: ensayo clínico aleatorizado, desarrollado con 40 pacientes aleatorizados por igual al grupo control (tratados con ácidos grasos esenciales) y al grupo experimental (tratados con 5% de propóleo verde) durante 30 días. Los resultados de interés fueron características sociodemográficas, clínicas y de laboratorio, características de la lesión, tales como tipo de tejido en el lecho, presencia de exudado, características del borde, contenido microbiano y dolor. Resultados: en cuanto a las características sociodemográficas, clínicas y de laboratorio, los dos grupos no mostraron diferencias estadísticamente significativas. Luego de la evaluación en 30 días, se observó efecto para ambos grupos tratados, pero para el grupo experimental mayor efectividad en cuanto al tipo de tejido del lecho, tipo de exudado, características de los bordes, contenido microbiano y dolor. Conclusion: la pomada a base de propóleo mostró un efecto curativo, presentándose como una herramienta potencial en la curación de úlceras crónicas.

RESUMO Objetivo: avaliar a eficácia da própolis verde brasileira a 5% (pomada) em indivíduos com úlceras crônicas. Métodos: ensaio clínico randomizado, desenvolvido com 40 pacientes aleatorizados igualmente para grupo controle (tratado com ácido graxo essencial) e grupo experimental (tratado com própolis verde a 5%) por 30 dias. Os desfechos de interesse foram características sociodemográficas, clínicas e laboratoriais, características das lesões, como tipo de tecido no leito, presença de exsudato, características da borda, conteúdo microbiano e dor. Resultados: quanto às características sociodemográficas, clínicas e laboratoriais, os dois grupos não apresentaram diferença estatisticamente significativas. Após avaliação em 30 dias, observou-se efeito para os dois grupos tratados, porém, para o grupo experimental, maior eficácia quanto ao tipo de tecido no leito, tipo de exsudato, característica da borda, conteúdo microbiano e dor. Conclusão: a pomada a base de própolis mostrou efeito cicatrizante, apresentando-se como potencial instrumento na cicatrização de úlceras crônicas.

Extraction, identification and antitumor activity in cell cultures of cubebin isolated from dry seeds Piper cubeba (Piperaceae).

The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30µg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth - a cytostatic effect, showing no cytocidal effect on any lineage cell.

Preclinical Effects Of Melatonin On The Development Of Ehrlich's Tumor: A Biochemical, Cognitive, And Molecular Approach.

BACKGROUND: It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects. OBJECTIVE: This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor. METHODS: Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs. RESULTS: Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment. CONCLUSION: In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

Pracaxi oil affects xenobiotic metabolisms, cellular proliferation, and oxidative stress without cytotogenotoxic effects in HepG2/C3A cells.

Pentaclethra macroloba (Willd.) Kuntze seeds oil has been used as a topical healing agent, applied mainly to parturients and snake bites. The objective was to investigate the effects of pracaxi oil (POP) on HepG2/C3A cells under cytogenotoxicity, cell cycle and apoptosis influence, and expression of metabolism and other related cell types proliferation genes. Cytotoxicity was analyzed by MTT test and apoptosis and cell cycle interferences by flow cytometry. To identify genotoxicity were used comet and micronucleus tests. RT-qPCR investigated gene expression. PO chemical characterization has shown two significant triterpenes, identified as oleanolic acid and hederagenin. The results showed that the PO did not reduce cell viability at concentrations ranging from 31 to 500 µg/ml. Comet and micronucleus assays revealed the absence of genotoxic effects, and flow cytometry showed no cell cycle or apoptosis disturbance. RT-qPCR indicated that PO up-regulated genes related to metabolism (CYP3A4, CYP1A2, CYP1A1), cell proliferation (mTOR), and oxidative stress (GPX1). The data indicate that PO has no cytogenotoxic effects and suggest that it activated the PI3/AKT/mTOR cascade of cell growth and proliferation. Inside the cells, the PO activated xenobiotic metabolizing genes, responsible for reactive oxygen species (ROS) generation, can neutralize ROS with increased GPX1 gene expression without genetic damage, interruption of the cell cycle, or induction of apoptosis.

In vivo toxicogenic potential of Salix alba (Salicaceae) bark extract.

Salix alba (white willow) bark extract is widely used for conditions associated with inflammation, fever, microbial infection or pain. Exposure of human cultured leukocytes to S. alba in vitro noted a genotoxic response. However, data regarding the influence of this bark extract on DNA damage in vivo are lacking. The main goal of this study was to examine the potential of S.alba bark extract to induce DNA damage and chromosome aberrations in an in vivo model using cells obtained from male Swiss albino mice administered the compound orally. The extract was administered by oral gavage daily for 7 days at doses of 500, 1000, or 2000 mg/kg b.w. Genotoxicity analysis was performed using the comet assay on peripheral blood leukocytes, as well as liver, bone marrow, heart, and testicular cells collected 4 hr after the last treatment and the micronucleus (MN) test on bone marrow cells. In essence cells were collected 28 hr after the penultimate treatment Data demonstrated that S. alba bark extract did not induce significant DNA damage in any cell types examined, or clastogenic/aneugenic effects as detected by the MN test at the three tested doses. Under these experimental conditions, evidence indicates that S.alba bark extract did not initiate genotoxic or chromosome aberrations in various mouse cells investigated.

Genotoxicity induced by nerol, an essential oil present in citric plants using human peripheral blood mononuclear cells (PBMC) and HepG2/C3A cells as a model.

Nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) is a monoterpene widely used in cosmetic products, household detergents and cleaners, as well as a flavoring in several food products. Despite the high level of human exposure to nerol, an absence of studies regarding potential genetic toxicity in human cells exists. The aim of this investigation was to examine the cytotoxic and genotoxic potential of this monoterpene on human peripheral blood mononuclear cells as well as hepatic metabolizing HepG2/C3A human cell line. Cytotoxicity was assessed using trypan blue staining and MTT assay while genotoxicity was determined utilizing the comet and micronucleus test. Cytotoxicity tests showed cell viability greater than 70% for concentrations between 2.5 and 500 µg/ml. Both cell types exhibited significant DNA damage and chromosomal mutations after medium and high concentration incubation with nerol indicating that the safety of use of this monoterpene in various formulations to which humans are exposed needs to be monitored and requires more comprehensive investigations.

Cytotoxic effects of Euterpe oleraceae fruit oil (açaí) in rat liver and thyroid tissues

Abstract Euterpe oleracea Mart., Arecaceae, fruit (açaí) presents considerable potential for the development of new medicines due to its phytochemical composition and antioxidant activity. More recently, special attention has been given to the pharmacological potential of the fruit's oil. This study analysed the histological and histochemical effects of different dosages of açaí oil on rat's liver and thyroid cells, in order to evaluate its cytotoxic potential after administration for consecutive days. Male Wistar rats were treated with the açaí oil by gavage at doses of 30, 100 and 300 mg/kg, for 14 days, within a 24 h interval. Liver and thyroid fragments were collected for histology (hematoxylin and eosin) and histochemistry analysis (blue of Nilo (lipids), Baker (lipids), bromophenol blue (protein), PAS (polysaccharides)). The results showed that animals exposed to açaí oil presented alterations in the liver cells, where the integrity of the liver tissue was increasingly lost as the açaí oil doses increased. Nuclear pyknosis was observed in several hepatocytes, evidencing the occurrence of cell death. Alteration in the amount of lipids, polysaccharides, vacuoles in the cytoplasm, and proliferation of Kupffer cells were observed in histochemical analyzes. As for the thyroid of the treated rats, alterations were observed in the size of the follicular lumen and also in the connective tissue found between the follicles. Under the experimental conditions employed in the present study, the cytotoxicity observed in this work is worrying, specially considering the liver, when frequent or continuous damage could lead pathological disorders in this organ.

Salix alba (white willow) medicinal plant presents genotoxic effects in human cultured leukocytes.

Salix alba (SA), commonly known as white willow, is a plant used in folk medicine for the treatment of chronic and acute inflammation, infection, pain, and fever. The phytochemical characterization of the bark extract of this plant indicated that its main component is salicin, a precursor of the anti-inflammatory agent acetylsalicylic acid. Considering the lack of studies evaluating the genetic toxicity and cytotoxic action of SA bark extract on human cells, as well as the chemical characterization of its major phenolic compounds, the present study was designed to (1) investigate the cytotoxic and genotoxic potential of SA bark extract on human peripheral leukocyte cells and human hepatoma cell line HepG2, and (2) characterize its major phenolic constituents. The phenolic compounds found were salicylic acid, salicin, salidroside, saligenin, tremulodin, salicoylsalicin, salicortin, and tremulacin. The results using trypan blue staining test showed viability decreases (viability less than 70%) for concentrations of SA extract equal and higher to 200 µg/ml. Low genotoxic activity (comet assay) was exhibited for 50 and 100 µg/ml SA extract in human leukocytes. SA did not exert a marked clastogenic/aneugenic effect on leukocytes and HepG2 human cells. Data suggest that the genotoxic effects of SA bark extract occur when it is not metabolized by liver enzymes.

The genotoxic effects of fruit extract of Crataegus oxyacantha (hawthorn) in mice.

Crataegus oxyacantha L. (Rosaceae) is a medicinal plant with a long history of use in European, Chinese, and American. The majority of pharmacological activities associated with fruit extracts of C. oxyacantha L. are related to cardio-stimulant properties utilized in the treatment of atherosclerosis, hypertension with myocardic insufficiency, angina pectoris, cardiac rhythm alterations, and heart failure. Some other therapeutic uses for renal calculi, dyspnea, as well as a diuretic, sedative, and anxiolytic were also reported. Due to the beneficial potential of C. oxyacantha fruits extract but evidence in vitro of genetic toxicity, the aim of the present study was to examine the genotoxic potential of plant extract in vivo in mice. The extract was administered orally, daily by gavage at doses of 50, 100, and 200 mg/kg body weight for seven days. Data demonstrated that C. oxyacantha extract did not markedly induce DNA damage in leukocytes and bone marrow cells by the comet assay; however, the extract produced a significant rise in micronucleated polychromatic erythrocytes (PCE) at all tested doses in a non-dose dependent manner as evidenced by the micronucleus test. The PCE/normochromatic erythrocytes (NCE) ratio indicated no significant cytotoxicity. Under our experimental conditions, C. oxyacantha fruits extract exhibited weak clastogenic and/or aneugenic effects in bone marrow cells of male mice, confirming our previous in vitro findings that this plant extract induced genotoxicity suggesting that prolonged or high dose use needs to be undertaken with caution.

Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells.

Crataegus oxyacantha, a plant of the Rosaceae family also known "English hawthorn, haw, maybush, or whitethorn," has long been used for medicinal purposes such as digestive disorders, hyperlipidemia, dyspnea, inducing diuresis, and preventing kidney stones. However, the predominant use of this plant has been to treat cardiovascular disorders. Due to a lack of studies on the genotoxicity of C. oxyacantha, this investigation was undertaken to determine whether its fruit extract exerts cytotoxic, genotoxic, or clastogenic/aneugenic effects in leukocytes and HepG2 (liver hepatocellular carcinoma) cultured human cells, or mutagenic effects in TA100 and TA98 strains of Salmonella typhimurium bacterium. Genotoxicity analysis showed that the extract produced no marked genotoxic effects at concentrations of 2.5 or 5 µg/ml in either cell type; however, at concentrations of 10 µg/ml or higher significant DNA damage was detected. The micronucleus test also demonstrated that concentrations of 10 µg/ml or higher produced clastogenic/aneugenic responses. In the Ames test, the extract induced mutagenic effects in TA98 strain of S. typhimurium with metabolic activation at all tested concentrations (2.5 to 500 µg/ml). Data indicate that, under certain experimental conditions, the fruit extract of C. oxyacantha exerts genotoxic and clastogenic/aneugenic effects in cultured human cells, and with metabolism mutagenicity occurs in bacteria cells.

High-performance thin-layer chromatography/desorption electrospray ionization mass spectrometry imaging of the crude extract from the peels of Citrus aurantium L. (Rutaceae).

RATIONALE: Citrus aurantium L. is a plant belonging to the Rutaceae family, whose extracts are extensively used in weight management products and as thermogenic agents. Here we present two methodologies to analyse the extracts obtained from the peels of Citrus aurantium L. that usually require multiple sample preparation and detection steps. METHODS: Polar compounds of the crude extract from the peels of Citrus aurantium L. (Rutaceae) were investigated by direct infusion electrospray ionization mass spectrometry (ESI-MS) and high-performance thin-layer chromatography (HPTLC) coupled to desorption electrospray ionization mass spectrometry (DESI-MS). ESI-MS was performed in both positive and negative ion modes. Molecular imaging of the HPTLC plates was used for the direct analysis of the phytocompounds present in the crude extract from the peels of Citrus aurantium L. by DESI-MS imaging. RESULTS: Characteristic mass spectra with many diagnostic ions were obtained from the extract analysis, allowing a fast and reliable identification of these species. Tandem mass spectrometry (MS/MS) was employed to confirm the identity of specific metabolites. CONCLUSIONS: HPTLC/DESI-MS imaging is a relatively fast, versatile, and efficient technique for natural product analysis, since many more ions are observed than with the direct infusion ESI-MS. The MS/MS technique provided information about the component structures, revealing the presence of important bioactive components. The application of DESI-MS imaging may contribute to the improvement identification and characterization of pharmacologically active compounds in phytochemistry.

In vivo evaluation of the genetic toxicity of Rubus niveus Thunb. (Rosaceae) extract and initial screening of its potential chemoprevention against doxorubicin-induced DNA damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus niveus Thunb. plant belongs to Rosaceae family and have been used traditionally to treat wounds, burns, inflammation, dysentery, diarrhea and for curing excessive bleeding during menstrual cycle. The present study was undertaken to investigate the in vivo genotoxicity of Rubus niveus aerial parts extract and its possible chemoprotection on doxorubicin (DXR)-induced DNA damage. In parallel, the main phytochemicals constituents in the extract were determined. MATERIALS AND METHODS: The animals were exposed to the extract for 24 and 48 h, and the doses selected were 500, 1000 and 2000 mg/kg b.w. administered by gavage alone or prior to DXR (30 mg/kg b.w.) administered by intraperitoneal injection. The endpoints analyzed were DNA damage in bone marrow and peripheral blood cells assessed by the alkaline alkaline (pH>13) comet assay and bone marrow micronucleus test. RESULTS AND CONCLUSION: The results of chemical analysis of the extract showed the presence of tormentic acid, stigmasterol, quercitinglucoronide (miquelianin) and niga-ichigoside F1 as main compounds. Both cytogenetic endpoints analyzed showed that there were no statistically significant differences (p>0.05) between the negative control and the treated groups with the two higher doses of Rubus niveus extract alone, demonstrating absence of genotoxic and mutagenic effects. Aneugenic/clastogenic effect was observed only at 2000 mg/kg dose. On the other hand, in the both assays and all tested doses were observed a significant reduction of DNA damage and chromosomal aberrations in all groups co-treated with DXR and extract compared to those which received only DXR. These results indicate that Rubus niveus aerial parts extract did not revealed any genotoxic effect, but presented some aneugenic/clastogenic effect at higher dose; and suggest that it could be a potential adjuvant against development of second malignant neoplasms caused by the cancer chemotherapic DXR.

Uncaria tomentosa (cat's claw) improves quality of life in patients with advanced solid tumors.

OBJECTIVE: Cat's claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients. METHODS: This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy - Fatigue questionnaires were used to assess the participants' quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. RESULTS: Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients' overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however, the disease stabilized for more than 8 months in four participants. The medication was well tolerated by most patients. CONCLUSION: Use of cat's claw might be beneficial in patients with advanced cancer by improving their quality of life and reducing fatigue. The mechanism of action does not seem to be related to the anti-inflammatory properties of this plant.

Genotoxic assessment of Rubus imperialis (Rosaceae) extract in vivo and its potential chemoprevention against cyclophosphamide-induced DNA damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus imperialis Cham. Schl. (Rosaceae) is frequently used in traditional medicine as hypoglycemic, antinociceptive and antiviral remedy. MATERIALS AND METHODS: Swiss albino mice were distributed in eight groups for acute treatment with Rubus imperialis extract (24 h). The extract doses selected were 50, 250 and 500 mg/kg b.w. administered by gavage alone or plus to CPA (50 mg/kg b.w.) administered by intraperitoneal injection. Control groups were treated in a similar way. Analyses were performed using the comet assay, on leukocytes (collected 4 and 24h after treatment) and liver (collected 24 h after treatment), and using the micronucleus test (MN) in bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). RESULTS AND CONCLUSION: The main compounds identified in the Rubus imperialis extract were saponins and steroidal compounds, with niga-ichigoside and tormentic acid being the major compounds. Tested doses of Rubus imperialis extract showed no genotoxic effects on leukocytes from peripheral blood or liver cells by the comet assay. However, the MN test showed an increase in the frequency of micronucleated cells at the two higher doses tested, indicating that this extract has clastogenic/aneugenic effects on bone marrow cells at higher doses. On the other hand, for all cells evaluated, the three tested doses of the Rubus imperialis extract promoted inhibition of DNA damage induced by CPA. Despite the chemoprevention observed, the clastogenicity/aneugenicity observed suggested caution about either continuous or high-dose usage of Rubus imperialis aerial parts extract by humans.

Endothelial, renal and hepatic variables in Wistar rats treated with Vancomycin.

Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.

Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model.

BACKGROUND: Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair growth stimulation and its toxicological aspects. METHODS: Mesocricetus auratus were randomly divided into three groups. Control group was treated with Aristoflex® gel, 1% group with the same gel but added 1% VEGF and 3% group with 3% VEGF. Biochemical, hematological and histological analyses were done. RESULTS: At the end of the experiment (15th day of VEGF treatment) efficacy was determined macroscopically by hair density dermatoscopy analysis, and microscopically by hair diameter analysis. They both demonstrated that hair of the VEGF group increased faster and thicker than control. On the other hand, biochemical and hematological results had shown that VEGF was not 100% inert. CONCLUSIONS: VEGF increased hair follicle area, but more studies are necessary to confirm its toxicity.

Evaluation of antimicrobial and antimalarial activities of crude extract, fractions and 4-nerolidylcathecol from the aerial parts of Piper umbellata L. (Piperaceae).

Presently, natural products, such as Piper umbellata L. (Piperaceae), have been evaluated as sources of antimicrobial agents with efficacies against microorganisms. The in vitro antimicrobial activity was performed by broth micro-dilution susceptibility assay, according to the protocols of the National Committee for Clinical Laboratory Standards, and described the antibacterial and antifungal activities of crude ethanolic extract and fractions obtained by partitions sequentially among water-methanol, methylene chloride and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol from the aerial parts of P. umbellata L. Amphotericin B and ciprofloxacin were used as controls. Among the microorganism cultures, hydromethanol fraction demonstrated the pre-eminent antifungal activity. 4-Nerolidylcathecol was the only tested plant component that exhibited activity against all the selected microorganisms, suggesting its great potential as a source for the development of new drugs. In order to estimate the antimalarial activity of P. umbellata L., a micro-dilution method protocol, parasite lactate dehydrogenase assay, with a Plasmodium falciparum Sierra Leone (D6) clone was utilised. The antimalarial agent artemisinin was used as control. 4-Nerolidylcathecol exhibited the best antimalarial activity; however, it was not significant when compared with control. These in vitro results do not justify the use of P. umbellata L. in malaria patients. However, there is a possibility of 4-nerolidylcathecol, after biotransformation, exhibiting a significant antimalarial activity in in vivo assays. However, 4-nerolidylcathecol demonstrated to possess a broad antimicrobial activity which is, in fact, a promising source for the development of new therapeutic agents.

Chemical composition and antimicrobial activity of essential oils from Chromolaena laevigata during flowering and fruiting stages.

The chemical compositions and antimicrobial activities of essential oils from the leaves, stems, capitula, and cypselas of Chromolaena laevigata were evaluated at two different phenological stages, flowering and fruiting. Thirty-eight compounds were identified in the crude oils by GC/MS. The sesquiterpene laevigatin was the major constituent of the leaf, capitulum, and cypsela oils, while the sesquiterpene spathulenol was the main component in the stem oils. The antimicrobial activities of the oils were evaluated against Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Stem oil obtained from Chromolaena laevigata during the fruiting stage generally showed the highest activity with minimum inhibitory concentration (MIC) values of 62.5 µg/ml against Candida albicans and S. aureus, and 500 µg/ml against P. aeruginosa and E. coli. Pure laevigatin exhibited MIC values of 500 and 125 µg/ml against C. albicans and S. aureus, respectively, indicating that this constituent could be responsible, at least in part, for the antimicrobial activities detected in the crude oils. More studies concerning the biological activities of isolated derivatives are required to improve our knowledge of the antimicrobial potential of volatile compounds present in native plants.