Subacute toxicology studies on the aqueous fraction of the ethanol extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) in dogs

Cissampelos sympodialis Eichl. (Menispermaceae) has been investigated about its botanical, chemical, pharmacological and toxicological aspects in our laboratory. Previous acute toxicology studies demonstrated that in dogs as well as in Wistar rats, 5 g/kg, p.o., and 2 g/kg, i.p. of the aqueous fraction of the ethanol extract of the leaves of Cissampelos sympodialis (AFL), induced a significant increase in the phosphatase alkaline and gama glutamil tranferase (GGT) levels, that were completely reversed in 15 days after interruption of AFL treatment. The aim of the present work was to investigate the subacute toxicology effects induced by AFL in dogs. We used the methods proposed by Portaria 116/96 of the Secretaria Nacional de Vigilância Sanitária, which regulates studies of toxicity for phytomedicines in Brazil. Daily administration (p.o.) of AFL, 45 mg/kg/day (5 times the dose used by human beings), during 4 weeks, was devoid of any effect on haematological (haemogram and platelets) and on blood biochemical parametes. In conclusion, the present study, using dogs, demonstrated that AFL, in a popularly used dose, by human beings, was devoid of any toxicological effect

Brief Research Report: Expression of PD-1 and CTLA-4 in T Lymphocytes and Their Relationship With the Periparturient Period and the Endometrial Cytology of Dairy Cows During the Postpartum Period

The present study sought to evaluate the expression of PD-1 and CTLA-4 in blood T lymphocytes during the periparturient period and their relationship with uterine health in dairy cows, as determined by endometrial cytology and serum concentrations of β-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFAs), which are indicators of a negative energy balance. The second objective of this study was to investigate whether the expression of PD-1 and CTLA-4 in T lymphocytes is associated with the serum acute phase-protein haptoglobin concentration during the periparturient period. To address these objectives, 26 clinically healthy dairy cows were used. Peripheral blood was collected 14 days prepartum (T-14), at calving (T0), and 30 days postpartum (T30) to measure the expression of PD-1 and CTLA-4 in blood T lymphocytes by flow cytometry. In addition, we collected blood at T0, 10 days after parturition (T10), and T30 to obtain serum and determine the serum concentrations of NEFA, BHB, and Hp. Endometrial cytology was performed at T10, 20 days after parturition (T20), and T30. In the present study, we observed higher expression of CTLA-4 and PD-1 in T lymphocytes at parturition and in the prepartum period, which could indicate a relationship between these immune checkpoints and immunological tolerance during gestation in dairy cattle. In addition, a negative association between the expression of these immune checkpoints prepartum or at parturition and endometrial cytology at T20 and T30 was observed, indicating the negative implications of these immune response regulators in susceptibility to infections. This finding was further corroborated by the relationship between the serum concentration of haptoglobin and the expression of CTLA-4 and PD-1 by T lymphocytes. However, we did not observe a relationship between the indicators of negative energy balance, evaluated by the serum concentrations of BHB and NEFA, and the expression of the immune checkpoint markers studied. Thus, our findings represent an initial step that paves the way for the development of new therapeutic alternatives directed by the host with the objective of increasing the resistance of dairy cattle to infections in this critical period of life

Aging: Molecular Pathways and Implications on the Cardiovascular System

The world’s population over 60 years is growing rapidly, reaching 22% of the global population in the next decades. Despite the increase in global longevity, individual healthspan needs to follow this growth. Several diseases have their prevalence increased by age, such as cardiovascular diseases, the leading cause of morbidity and mortality worldwide. Understanding the aging biology mechanisms is fundamental to the pursuit of cardiovascular health. In this way, aging is characterized by a gradual decline in physiological functions, involving the increased number in senescent cells into the body. Several pathways lead to senescence, including oxidative stress and persistent inflammation, as well as energy failure such as mitochondrial dysfunction and deregulated autophagy, being ROS, AMPK, SIRTs, mTOR, IGF-1, and p53 key regulators of the metabolic control, connecting aging to the pathways which drive towards diseases. In addition, senescence can be induced by cellular replication, which resulted from telomere shortening. Taken together, it is possible to draw a common pathway unifying aging to cardiovascular diseases, and the central point of this process, senescence, can be the target for new therapies, which may result in the healthspan matching the lifespan

Comparison of the hypotensive effect induced by the ethanol extract of <i>Albizia inopinata</i> G. P. Lewis in normotensive and chronically L-NAME hypertensive rats

El objetivo del presente estudio fue caracterizar la respuesta hipotensora provocada por la fracción acuosa del extracto etanólico de hojas (AFL) de Albizia inopinata en ratas normotensas y hipertensas por el L-NAME (N-nitro-L-argininA metiléster). En las ratas normotensas, AFL provocó una disminución dosis-dependiente de la presión arterial, acompãnada de un aumento de la frecuencia cardíaca. Ya en el caso de las ratas hipertensas, AFL provocó una hipotensión más aguda, en tanto que las modificaciones de la frecuencia cardíaca no fueron significativas. En los anillos de la aorta, concentraciones crecientes de AFL antagonizaron las contracciones provocadas por fenilefrina y KCl; por otro lado, los valores de CI 50 para ratas normotensas fueron significantemente superiores a los obtenidos en ratas hipertensas. El efecto vasodilator de AFL parece ser claramente dependiente de la liberación de NO por el endotelio vascular. En conclusión, el presente estudio demuestra que AFL disminuye la presión arterial en ratas normotensas e hipertensas, debido probablemente a una disminución de la resistencia periférica total. El efecto hipotensor mayor observado en ratas hipertensas es causado probablemente por una vasodilatación potencializada, provocada por AFL.The aim of this study was to characterize the hypotensive response induced by the aqueous fraction of the ethanolic extract of the leaves (AFL) of Albizia inopinata in normotensive and chronically L-NAME-hypertensive rats. AFL induced dosedependent decreases in mean blood pressure (MAP) in both cases, however, hypotension was more pronounced in hypertensive rats. In isolated rat aortic rings, increasing concentrations of AFL were able to antagonize phenylephrine and KCl-induced contractions, however, IC 50 values for normotensive rats were significantly higher than that obtained for hypertensive rats. Furthermore, AFL-induced response was clearly endothelium-dependent since after removal of aortic endotelial cells and NO-synthase blockade, the relaxant response was significantly attenuated. The present work demonstrates that in normotensive and L-NAME-hypertensive rats, AFL lowers MAP, probably due to a decrease in peripheral resistances. The more pronounced hypotensive effect observed in hypertensive rats, is probably due to a strong vasodilation induced by AFL in these rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Comparison of the hypotensive effect induced by the ethanol extract of <i>Albizia inopinata</i> G. P. Lewis in normotensive and chronically L-NAME hypertensive rats

El objetivo del presente estudio fue caracterizar la respuesta hipotensora provocada por la fracción acuosa del extracto etanólico de hojas (AFL) de Albizia inopinata en ratas normotensas y hipertensas por el L-NAME (N-nitro-L-argininA metiléster). En las ratas normotensas, AFL provocó una disminución dosis-dependiente de la presión arterial, acompãnada de un aumento de la frecuencia cardíaca. Ya en el caso de las ratas hipertensas, AFL provocó una hipotensión más aguda, en tanto que las modificaciones de la frecuencia cardíaca no fueron significativas. En los anillos de la aorta, concentraciones crecientes de AFL antagonizaron las contracciones provocadas por fenilefrina y KCl; por otro lado, los valores de CI 50 para ratas normotensas fueron significantemente superiores a los obtenidos en ratas hipertensas. El efecto vasodilator de AFL parece ser claramente dependiente de la liberación de NO por el endotelio vascular. En conclusión, el presente estudio demuestra que AFL disminuye la presión arterial en ratas normotensas e hipertensas, debido probablemente a una disminución de la resistencia periférica total. El efecto hipotensor mayor observado en ratas hipertensas es causado probablemente por una vasodilatación potencializada, provocada por AFL.The aim of this study was to characterize the hypotensive response induced by the aqueous fraction of the ethanolic extract of the leaves (AFL) of Albizia inopinata in normotensive and chronically L-NAME-hypertensive rats. AFL induced dosedependent decreases in mean blood pressure (MAP) in both cases, however, hypotension was more pronounced in hypertensive rats. In isolated rat aortic rings, increasing concentrations of AFL were able to antagonize phenylephrine and KCl-induced contractions, however, IC 50 values for normotensive rats were significantly higher than that obtained for hypertensive rats. Furthermore, AFL-induced response was clearly endothelium-dependent since after removal of aortic endotelial cells and NO-synthase blockade, the relaxant response was significantly attenuated. The present work demonstrates that in normotensive and L-NAME-hypertensive rats, AFL lowers MAP, probably due to a decrease in peripheral resistances. The more pronounced hypotensive effect observed in hypertensive rats, is probably due to a strong vasodilation induced by AFL in these rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Inhibitory effect of beta-pinene, alpha-pinene and eugenol on the growth of potential infectious endocarditis causing Gram-positive bacteria Efeito inibitório de eugenol, beta-pineno e alfa-pineno sobre o crescimento de bactérias Gram-positivas potencialmente causadoras de endocardite infecciosa

This study was led with the purpose of evaluating the effectiveness of eugenol, beta-pinene and alpha-pinene in inhibiting the growth of potential infectious endocarditis causing gram-positive bacteria. The phytochemicals Minimum Inhibitory Concentration-MIC was determined by solid medium diffusion procedure, while the interference of the MIC values on the bacterial cell viability was performed by viable cells count. Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae and S. pyogenes strains were used as test microorganisms. The assayed phytochemicals showed effectiveness in inhibiting all assayed bacteria strains presenting MIC values between 2.5 and 40 µL/mL. Eugenol showed the lowest MIC values which were between 2.5 and 5 µL/mL for the most bacteria strains. MIC values found to the phytochemicals were able to inhibit the cell viability of S. aureus providing a total elimination of the bacteria inoculum in a maximum time of 24 hours of exposure. These data showed the interesting antibacterial property of the assayed phytochemicals and support their possible and rational use in the antimicrobial therapy.<br>Este estudo foi conduzido com a proposta de avaliar a efetividade de eugenol, beta-pineno e alfa-pineno em inibir o crescimento de cepas de bactérias Gram-positivas potencialmente causadoras de endocardite infecciosa. A Concentração Inibitória Mínima-CIM dos fitoconstituintes foi determinada através do método de difusão em meio sólido, enquanto a interferência da CIM sobre a viabilidade celular bacteriana foi avaliada através da contagem de células viáveis. Cepas de Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae e S. pyogenes foram utilizadas como microrganismos teste nos ensaios antimicrobianos. Os fitoconstituintes ensaiados mostraram efetividade em inibir todas as cepas bacterianas utilizadas como microrganismos testes apresentando valores de CIM entre 2.5 e 40 µL/mL. Eugenol apresentou os menores valores de CIM, os quais estiveram entre 2,5 e 5 µL/mL para a maioria das cepas bacterianas. Os valores de CIM encontrados para os fitoconstituintes foram capazes de inibir a viabilidade celular de S. aureus causando uma total eliminação do inóculo bacteriano em um tempo máximo de 24 horas de exposição. Estes dados mostram o intenso potencial antibacteriano dos fitoconstituintes ensaiados e suportam sua possível e racional aplicação na terapia antimicrobiana

Efeito inibitório de eugenol, beta-pineno e alfa-pineno sobre o crescimento de bactérias Gram-positivas potencialmente causadoras de endocardite infecciosa

This study was led with the purpose of evaluating the effectiveness of eugenol, beta-pinene and alpha-pinene in inhibiting the growth of potential infectious endocarditis causing gram-positive bacteria. The phytochemicals Minimum Inhibitory Concentration-MIC was determined by solid medium diffusion procedure, while the interference of the MIC values on the bacterial cell viability was performed by viable cells count. Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae and S. pyogenes strains were used as test microorganisms. The assayed phytochemicals showed effectiveness in inhibiting all assayed bacteria strains presenting MIC values between 2.5 and 40 µL/mL. Eugenol showed the lowest MIC values which were between 2.5 and 5 µL/mL for the most bacteria strains. MIC values found to the phytochemicals were able to inhibit the cell viability of S. aureus providing a total elimination of the bacteria inoculum in a maximum time of 24 hours of exposure. These data showed the interesting antibacterial property of the assayed phytochemicals and support their possible and rational use in the antimicrobial therapy.Este estudo foi conduzido com a proposta de avaliar a efetividade de eugenol, beta-pineno e alfa-pineno em inibir o crescimento de cepas de bactérias Gram-positivas potencialmente causadoras de endocardite infecciosa. A Concentração Inibitória Mínima-CIM dos fitoconstituintes foi determinada através do método de difusão em meio sólido, enquanto a interferência da CIM sobre a viabilidade celular bacteriana foi avaliada através da contagem de células viáveis. Cepas de Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae e S. pyogenes foram utilizadas como microrganismos teste nos ensaios antimicrobianos. Os fitoconstituintes ensaiados mostraram efetividade em inibir todas as cepas bacterianas utilizadas como microrganismos testes apresentando valores de CIM entre 2.5 e 40 µL/mL. Eugenol apresentou os menores valores de CIM, os quais estiveram entre 2,5 e 5 µL/mL para a maioria das cepas bacterianas. Os valores de CIM encontrados para os fitoconstituintes foram capazes de inibir a viabilidade celular de S. aureus causando uma total eliminação do inóculo bacteriano em um tempo máximo de 24 horas de exposição. Estes dados mostram o intenso potencial antibacteriano dos fitoconstituintes ensaiados e suportam sua possível e racional aplicação na terapia antimicrobiana

Warifteine And Milonine, Alkaloids Isolated From Cissampelos Sympodialis Eichl: Cytotoxicity On Rat Hepatocyte Culture And In V79 Cells.

Two alkaloids were isolated from the leaves of Cissampelos sympodialis; a bisbenzylisoquinoline compound named warifteine and a novel 8,14-dihydromorphinandienone alkaloid named milonine. The cytotoxic effects of these alkaloids were assayed in cultured hepatocytes and V79 fibroblasts. Three independent endpoint assays for cytotoxicity in vitro were used: the nucleic acid content (NAC), tetrazolium reduction (MTT) and neutral red uptake (NRU). Milonine was less toxic than warifteine in both cell cultures. The IC50 values determined in the three different viability assays were around 100 and 400 microM after milonine treatment of V79 cells or hepatocytes. IC50 values ranging from 10 to 35 microM were obtained for warifteine in the viability tests evaluated in V79 cells and hepatocytes. Due to the similar cytotoxic effects detected on V79 cells and hepatocytes, probably warifteine and milonine induced toxic effects independent to the cytochrome P450. This hypothesis was corroborated by the results where Cimetidine (1.0 mM), a traditional cytochrome P450 inhibitor, did not protect the cells from the toxic action of warifteine or milonine. In conclusion, these alkaloids merit further investigations as potential novel pharmacological agents although milonine was less toxic than warifteine in the cells models investigated.142143-5

Accuracy of information on herbal medicines (phytoterapeutics agents) advertisements published in Paraíba, Brazil

Este estudo tem como objetivo avaliar a adequação legal da propaganda e publicidade de medicamentos fitoterápicos anunciada na Paraíba através de peças publicitárias obtidas na forma de impressos, os quais foram coletados em consultórios médicos, hospitais públicos e privados, farmácias e congressos. Verificou-se que as 53 propagandas coletadas promoveram 351 fitoterápicos, anunciando 140 plantas diferentes. A análise do material evidenciou irregularidades que ferem a legislação vigente: a RDC N° 102/2000 e a RDC N° 48/2004 da ANVISA (Agência Nacional de Vigilância Sanitária), regulamentadoras da propaganda de medicamentos e do registro de fitoterápicos respectivamente. A promoção de propagandas mais éticas para medicamentos é de interesse da ANVISA, além de ser extremamente importante para a população que é sempre a maior vítima das irregularidades.The aim of this study is to evaluate the advertisements accuracy of herbal medicines (phytoterapeutic agents) published in Paraíba through data obtained in the form of printed ads (leaflets) collected at medical clinics, public and private hospitals, drugstores and medical congress. It was verified that the 53 collected ads promoted 351 herbal medicines, announcing 140 different plants. The analysis of the ads evidenced irregularities according to Brazilian regulatory guidelines: RDC N° 102/2000 and RDC N° 48/2004, wich regulate advertisements and herbal medicines respectively. The promotion of more ethical ads for medicines is one the most important interest of the ANVISA (National Agency of Sanitary Surveillance), besides being an extremely important fact for the population that is always the largest victim of the irregularities.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Accuracy of information on herbal medicines (phytoterapeutics agents) advertisements published in Paraíba, Brazil

Este estudo tem como objetivo avaliar a adequação legal da propaganda e publicidade de medicamentos fitoterápicos anunciada na Paraíba através de peças publicitárias obtidas na forma de impressos, os quais foram coletados em consultórios médicos, hospitais públicos e privados, farmácias e congressos. Verificou-se que as 53 propagandas coletadas promoveram 351 fitoterápicos, anunciando 140 plantas diferentes. A análise do material evidenciou irregularidades que ferem a legislação vigente: a RDC N° 102/2000 e a RDC N° 48/2004 da ANVISA (Agência Nacional de Vigilância Sanitária), regulamentadoras da propaganda de medicamentos e do registro de fitoterápicos respectivamente. A promoção de propagandas mais éticas para medicamentos é de interesse da ANVISA, além de ser extremamente importante para a população que é sempre a maior vítima das irregularidades.The aim of this study is to evaluate the advertisements accuracy of herbal medicines (phytoterapeutic agents) published in Paraíba through data obtained in the form of printed ads (leaflets) collected at medical clinics, public and private hospitals, drugstores and medical congress. It was verified that the 53 collected ads promoted 351 herbal medicines, announcing 140 different plants. The analysis of the ads evidenced irregularities according to Brazilian regulatory guidelines: RDC N° 102/2000 and RDC N° 48/2004, wich regulate advertisements and herbal medicines respectively. The promotion of more ethical ads for medicines is one the most important interest of the ANVISA (National Agency of Sanitary Surveillance), besides being an extremely important fact for the population that is always the largest victim of the irregularities.Colegio de Farmacéuticos de la Provincia de Buenos Aire