Antitumor activity of solamargine in mouse melanoma model: relevance to clinical safety.

Melanoma is the most aggressive type of skin cancer, and thus it is important to develop new drugs for its treatment. The present study aimed to examine the antitumor effects of solamargine a major alkaloid heteroside present in Solanum lycocarpum fruit. In addition solamargine was incorporated into nanoparticles (NP) of yttrium vanadate functionalized with 3-chloropropyltrimethoxysilane (YVO4:Eu3+:CPTES:SM) to determine antitumor activity. The anti-melanoma assessment was performed using a syngeneic mouse melanoma model B16F10 cell line. In addition, systemic toxicity, nephrotoxic, and genotoxic parameters were assessed. Solamargine, at doses of 5 or 10 mg/kg/day administered subcutaneously to male C57BL/6 mice for 5 days, decreased tumor size and frequency of mitoses in tumor tissue, indicative of a decrease in cell proliferation. Treatments with YVO4:Eu3+:CPTES:SM significantly reduced the number of mitoses in tumor tissue, associated with no change in tumor size. There were no apparent signs of systemic toxicity, nephrotoxicity, and genotoxicity initiated by treatments either with solamargine alone or plant alkaloid incorporated into NP. The animals treated with YVO4:Eu3+:CPTES:SM exhibited significant increase in spleen weight accompanied by no apparent histological changes in all tissues examined. In addition, animals treated with solamargine (10 mg/kg/day) and YVO4:Eu3+:CPTES:SM demonstrated significant reduction in hepatic DNA damage which was induced by tumor growth. Therefore, data suggest that solamargine may be considered a promising candidate in cancer therapy with no apparent toxic effects.

Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells.

Glycoalkaloids have been widely demonstrated as potential anticancer agents. However, the chemosensitizing effect of these compounds with traditional chemotherapeutic agents has not been explored yet. In a quest for novel effective therapies to treat bladder cancer (BC), we evaluated the chemosensitizing potential of glycoalkaloidic extract (GE) with cisplatin (cDDP) in RT4 and PDX cells using 2D and 3D cell culture models. Additionally, we also investigated the underlying molecular mechanism behind this effect in RT4 cells. Herein, we observed that PDX cells were highly resistant to cisplatin when compared to RT4 cells. IC50 values showed at least 2.16-folds and 1.4-folds higher in 3D cultures when compared to 2D monolayers in RT4 cells and PDX cells, respectively. GE + cDDP inhibited colony formation (40%) and migration (28.38%) and induced apoptosis (57%) in RT4 cells. Combination therapy induced apoptosis by down-regulating the expression of Bcl-2 (p < 0.001), Bcl-xL (p < 0.001) and survivin (p < 0.01), and activating the caspase cascade in RT4 cells. Moreover, decreased expression of MMP-2 and 9 (p < 0.01) were observed with combination therapy, implying its effect on cell invasion/migration. Furthermore, we used 3D bioprinting to grow RT4 spheroids using sodium alginate-gelatin as a bioink and evaluated the effect of GE + cDDP on this system. Cell viability assay showed the chemosensitizing effect of GE with cDDP on bio-printed spheroids. In summary, we showed the cytotoxicity effect of GE on BC cells and also demonstrated that GE could sensitize BC cells to chemotherapy.

Antigenotoxic and Antioxidant Properties of Solanum cernuum and Its Alkaloid, Cernumidine.

Solanum cernuum VE. has been used extensively for the treatment of urinary disorders, gonorrhea and skin infections; cernumidine is a major component of S. cernuum (SC) hydroalcoholic extract. The micronucleus test in V79 cells was used to evaluate the genotoxic and antigenotoxic potential of SC and cernumidine. For antigenotoxicity assessment, methyl methanesulfonate (MMS, 44 µg/mL) and hydrogen peroxide (H2O2, 3.5 µg/mL) were added as inducers of chromosome damage. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Significantly higher frequencies of micronuclei were observed in cell cultures treated with SC concentrations of 160 and 320 µg/mL in comparison with the negative control, demonstrating a genotoxic effect. There was no significant difference in the frequency of micronuclei between cell cultures treated with a combination of SC and MMS and those treated only with MMS. On the other hand, a significant reduction in the frequency of micronuclei was observed for V79 cells treated with SC or cernumidine plus H2O2 compared to those treated only with H2O2. Furthermore, SC and cernumidine were able to scavenge free radicals in the DPPH assay. Thus, the protective effect of SC and cernumidine against H2O2 can be attributed to antioxidant activity.

Distinctive histopathology and modulation of cytokine production during oral and intraperitoneal Trypanosoma cruzi Y strain infection.

Acute Chagas disease outbreaks are related to the consumption of food or drink contaminated by triatomine feces, thus making oral infection an important route of transmission. Both vector-borne and oral infections trigger important cardiac manifestations in the host that are related to a dysregulated immune response. The aims of this work were to evaluate possible alterations of lymphocyte CD4+/CD8+ sub-populations, Th1 and Th2 cytokines, nitrite concentrations and cardiac histopathology. One group of male Wistar rats was intraperitoneally infected (I.P.) with 1×105 metacyclic trypomastigotes of the T. cruzi Y strain, and another group of Wistar rats was orally infected (O.I.) with 8×105 metacyclic trypomastigotes of the same strain. The intraperitoneal infection triggered statistically enhanced parasite and peritoneal macrophage numbers, increased concentrations of NO and IL-12 and elevated cardiac inflammatory foci when compared with the oral infection. However, proliferation of CD4+ and CD8+ T cells were not statistically different for oral and intraperitoneal routes.

Protective actions of melatonin against heart damage during chronic Chagas disease.

Chronic cardiomyopathy is the most important clinical form of Chagas disease, and it is characterised by myocarditis that is associated with fibrosis and organ dysfunction. Alternative treatment options are important tools to modulate host immune responses. The main goal of this work was to evaluate the anti-inflammatory actions of melatonin during the chronic phase of Chagas disease. TNF-α, IL-10 and nitrite concentrations were evaluated as predictive factors of immune modulation. Creatine phosphokinase-MB (CK-MB), cardiac inflammatory foci and heart weight were assessed to evaluate the efficacy of the melatonin treatment. Male Wistar rats were infected with 1×10(5) blood trypomastigotes of the Y strain of Trypanosoma cruzi and kept untreated for 60 days to mimic chronic infection. After this period, the rats were orally treated with melatonin 50mg/kg/day, and the experiments were performed 90, 120, and 180 days post-infection. Melatonin treatment significantly increased the concentration of IL-10 and reduced the concentrations of NO and TNF-α produced by cardiomyocytes. Furthermore, it led to decreased heart weight, serum CK-MB levels and inflammatory foci when compared to the untreated and infected control groups. We conclude that melatonin therapy is effective at protecting animals against the harmful cardiac inflammatory response that is characteristic of chronic T. cruzi infection.

Immunomodulatory effect of the alkaloidic extract of Solanum lycocarpum fruits in mice infected with Schistosoma mansoni.

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma; it accounts for more than 280,000 deaths annually. In this work we investigated the effect of the alkaloidic extract obtained by acid-base extraction of the dried fruits of Solanum lycocarpum on schistosomiasis. We used this extract at concentrations of 10, 20, and 40 mg/kg to treat mice infected with Schistosoma mansoni in different phases of the parasite cycle, and we compared its effect with that of the positive control praziquantel (60 mg/kg). We evaluated the results on the basis of the number of macrophages, eggs, and granulomas; we also assessed nitric oxide (NO) and interferon-gamma (IFN-γ) production. Animals treated with a daily dose of 10 or 20 mg/kg alkaloidic extract between the 37th and 41st day of infection showed increased number of macrophages, elevated NO and IFN-γ concentrations, and reduced number of eggs and granulomas in the liver. The alkaloidic extract of S. lycocarpum fruits displayed an immunomodulatory effect on mice infected with S. mansoni, so its potential to treat schistosomiasis deserves further studies.

A Validated Reverse Phase HPLC Analytical Method for Quantitation of Glycoalkaloids in Solanum lycocarpum and Its Extracts.

Solanum lycocarpum (Solanaceae) is native to the Brazilian Cerrado. Fruits of this species contain the glycoalkaloids solasonine (SN) and solamargine (SM), which display antiparasitic and anticancer properties. A method has been developed for the extraction and HPLC-UV analysis of the SN and SM in different parts of S. lycocarpum, mainly comprising ripe and unripe fruits, leaf, and stem. This analytical method was validated and gave good detection response with linearity over a dynamic range of 0.77-1000.00 µg mL(-1) and recovery in the range of 80.92-91.71%, allowing a reliable quantitation of the target compounds. Unripe fruits displayed higher concentrations of glycoalkaloids (1.04% ± 0.01 of SN and 0.69% ± 0.00 of SM) than the ripe fruits (0.83% ± 0.02 of SN and 0.60% ± 0.01 of SM). Quantitation of glycoalkaloids in the alkaloidic extract gave 45.09% ± 1.14 of SN and 44.37% ± 0.60 of SM, respectively.

Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits.

Solanum lycocarpum (Solanaceae), a Brazilian medicinal plant known as "wolf fruit," contains about 1.5% of glycoalkaloids in its dried fruits, consisting mainly of solamargine and solasonine. The present work reports the obtainment of the alkaloidic extract of the S. lycocarpum fruit by acid-base extraction and the isolation of the major alkaloid heterosides by chromatographic means, as well as the evaluation of their in vitro schistosomicidal activities. The in vitro schistosomicidal activities of the alkaloidic extract of S. lycocarpum fruits and its isolated steroidal alkaloids were undertaken against adult worms of Schistosoma mansoni. The alkaloidic extract (20, 32, and 50 µg mL(-1)), solasonine (50 µM), solamargine (32 and 50 µM), and equimolar mixture of glycoalkaloids (20, 32, and 50 µM) lead to the separation of all couple worms and extensive disruption on their teguments, such as sloughing, as well as their deaths within 24 h of incubation. In addition, the alkaloidic extract (10 and 15 µg mL(-1)), solasonine (50 µM), solamargine (10, 15, and 20 µM), and equimolar mixtures of glycoalkaloids (10 and 15 µM) reduced the development of eggs produced by the adult worms. Solamargine, containing the sugar chain moiety chacotriose, was more active than the solasonine, which contains solatriose sugar chain moiety. A synergistic effect was also observed for a mixture of solamargine and solasonine. Therefore, the alkaloidic extract of S. lycocarpum, and its major components, solamargine and solasonine, showed promising schistosomicidal activity.

Conhecimento, prática e atitude dos farmacêuticos hospitalares frente aos erros de medicação / Knowledge, attitude and practice of hospital pharmacists in the face of medication errors

A utilização de medicamentos é um processo complexo, que envolve vários serviços e setores. Os erros de medicação (EM) que acontecem durante o trabalho dos profissionais de saúde, podem gerar sérias consequências para os pacientes e para a organização hospitalar. Pelo fato do profissional farmacêutico avaliar a prescrição médica e dispensar o medicamento, ele pode contribuir para a ocorrência de um erro ou sua prevenção. Este estudo analisou no serviço de farmácia do Hospital Universitário/UFJF o conhecimento, a atitude e prática (CAP) dos farmacêuticos frente aos EM. Os dados foram obtidos através de um questionário do tipo CAP. Nos resultados foram apontados como responsáveis pelos EM tanto os fatores individuais (falta de atenção (6,34%), falta de conhecimento (5,98%), cansaço e estresse (5,63%)) como os fatores do sistema (excesso de trabalho (5,28%), falta de profissionais no setor (4,93%) e iluminação inadequada (3,52%)). Para minimizar tais erros os participantes da pesquisa destacaram: informatização da prescrição médica (13,45%), educação continuada, reciclagem e treinamento dos profissionais (13,45%). Em relação às providências tomadas após a ocorrência do erro, foram priorizadas nos questionários: orientação (32,15%), reuniões e debates sobre os erros, avaliação dos erros (28,57%) e notificação da ocorrência (25%). Os profissionais participantes desse estudo apresentam um conhecimento adequado sobre o assunto, uma atitude que não responsabiliza somente o indivíduo pelos EM, uma prática que transforma o erro em aprendizado e que previne muitas das ocorrências pela intervenção farmacêutica.

Drug use is a complex process that involves multiple services and health professionals. And medication errors (ME) are part of the work of these professionals, with serious consequences for patients and hospital organization. Due to the pharmacists to evaluate the prescription and dispense the drug, they can contribute to the error or prevent from occurring. Therefore, this work identified and analyzed the University Hospital/UFJF knowledge, attitude and practice (KAP) of hospital pharmacists in the face of ME. The data were obtained through a questionnaire. In results were identified as responsible for ME individual factors like inattention (6.34%), lack of knowledge (5.98%), fatigue, stress (5.63% ) as well as system factors: excess work (5.28%), inadequate lighting (4.93%) among other. Suggestions to minimize ME were also directed to the individual and the system: typed prescription (13.45%), continuing education, retraining and vocational training (13.45%) were the points highlighted by the participants. After the occurrence of the error, orientation (32.15%), meetings and discussions about the errors, evaluating them (28.57%), and notification of the occurrence (25%) were prioritized in questionnaires. This study showed that professionals in the Pharmacy Service of the University Hospital /UFJF have adequate knowledge on the subject, an attitude that not only the individual responsible for medication errors and a practice that transforms the learning and error that prevents some errors administration of drugs through pharmaceutical intervention

Uso etnomedicinal do chá de Morus nigra L. no tratamento dos sintomas do climatério de mulheres de Muriaé, Minas Gerais, Brasil / Ethnomedicinal use of tea from Morus nigra L. in the treatment of the climacteric symptoms in women from Muriaé, Minas Gerais, Brazil

Morus nigra L. (Moraceae), conhecida como amoreira, é usada popularmente, entre outros fins medicinais, para reposição hormonal. O objetivo do presente estudo foi avaliar o uso etnomedicinal do chá das folhas de M. nigra no tratamento dos sintomas do climatério. A pesquisa se baseou na aplicação de um questionário semiestruturado em mulheres residentes em Muriaé ? MG, que utilizavam chá de amoreira. A análise quantitativa foi determinada pela concordância de uso popular corrigida (CUPc). As características das mulheres entrevistadas foram: faixa etária entre 32 e 61 anos, cinco donas de casa, oito católicas, quatro com ensino fundamental incompleto e cinco haviam tido menopausa. Além de outros fins medicinais, nove das mulheres usavam o chá de amoreira para amenizar sintomas do climatério, resultando em uma CUPc de 90%. As amigas e os médicos foram as principais fontes de recomendação do uso do chá nas formas de infusão ou de decocção, com variação de dosagem e de aprazamento. Gases, aumento do apetite e diurese foram os efeitos adversos relatados, sendo que quatro das mulheres já tinham feito terapia hormonal para alívio dos sintomas do climatério. Os resultados confirmam a utilização do chá de M. nigra no tratamento de sintomas do climatério, apresentando um alto consenso de informação.

Morus nigra L. (Moraceae), known as mulberry, is used in folk medicine, including hormone replacement. The objective of this study was to evaluate the ethnomedicinal use of the tea of the leaves of M. nigra in the treatment of climacteric symptoms. The research was based on the application of a semi-structured questionnaire in women from city of Muriaé, Minas Gerais state, Brazil, which reported the use of the tea from mulberry. The quantitative analysis was based on the corrected popular use concordance (cPUC). The characteristics of the interviewed women were: aged 32 to 61 years, 5 housewives, 8 catholic, 4 with incomplete primary education, and 5 have had menopause. In addition to other medical purposes, 9 of the women used the mulberry tea to alleviate symptoms of menopause, resulting in a cPUC of 90%. The main recommendation of use was made by friends (6) and physicians (2), under infusion (7) or decoction (3) forms, with a range of dosing and administration. Gases, increased appetite and urine output were the adverse effects reported, and 4 of women had already used hormonal therapy to relieve the symptoms of menopause. The results confirm the use of tea from M. nigra in the treatment of climacteric symptoms, with high consensus information.

Analgesic and anti-inflammatory properties of essential oil from Ageratum fastigiatum

The chemical composition, analgesic and anti-inflammatory properties of essential oil from Ageratum fastigiatum were investigated. The main compounds found in the essential oil were germacrene D, α-humulene and β-cedrene. The oil, with LD50 of 2.50 g/kg, inhibited the acetic acid-induced writhing at the dose of 200 mg/kg. In the formalin test, the oil inhibited the first phase (200 mg/kg) and the second phase (100 mg/kg and 200 mg/kg). In the hot plate test, after 30 and 60 min of treatment the doses of 100 and 200 mg/kg increased the reaction time. The antiedematogenic effect, reduction on the exudate volume and leukocyte mobilization were observed at the doses of 100 and 200 mg/kg. The results indicated that A. fastigiatum possessed the analgesic and anti-inflammatory properties that supported the popular medicinal use of the plant.

A composição química e as propriedades analgésica e antiinflamatória do óleo essencial de Ageratum fastigiatum foram investigadas. Os principais constituintes do óleo essencial foram germacreno D, α-humuleno e β-cedreno. O óleo, com DL50 de 2,50 g/kg, inibiu as contorções abdominais induzidas por ácido acético na dose de 200 mg/kg. No teste da formalina, o óleo inibiu a primeira fase (200 mg/kg) e a segunda fase (100 e 200 mg/kg). O tempo de latência aumentou no teste da placa quente, após 30 e 60 minutos de tratamento, nas doses de 100 e 200 mg/kg. O efeito antiedematogênico, assim como a redução do volume do exsudato e da migração leucocitária foram observados nas doses de 100 e 200 mg/kg. Os resultados indicam que o A. fastigiatum possui propriedades analgésica e antiinflamatória, o que corrobora com o uso popular da planta.