Bixa orellana ethyl acetate fraction and its isolated compound ellagic acid attenuate the progression of MIA-induced osteoarthritis in rat knees.

Osteoarthritis (OA) is a pathology that is characterized by progressive erosion of articular cartilage. In this context, medicinal plants have become relevant tools regarding their potential role in the prevention and treatment of OA, being safe and effective. The aim of this work was investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of OA induced by monosodium iodoacetate (MIA) in rats. The plant material was extracted via maceration with 70 % hydroalcoholic solvent (BoHE). The ethyl acetate (BoEA) fraction was by solvents in increasing order of polarity. The ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-DAD) and analytical curve. The OA was induced using MIA in the right knee at the knee joint. Doses of BoEA and ElAc were administered daily (every 24 h, orally) at concentrations of 50, 100 and 50 mg/kg, respectively, for 28 days after induced OA. We evaluated the animals through clinical and radiological examinations every 7 days and, on the 29th day, the animals were euthanized, the joints being removed for histopathological analysis and the serum for cytokine analysis. BoEA and ElAc compounds reduced inflammation and nociception in OA and were as effective as indomethacin in clinical parameters of joint discomfort and allodynia in rats, in addition to showing improvements in radiological and histopathological images, acting on the progress of cartilage deterioration, proving properties related to anti-inflammatory and analgesic processes, being important allies for new therapeutic interventions for the treatment of OA.

Characterization, antimicrobial and cytotoxic activity of polymer blends based on chitosan and fish collagen.

This study aims to produce, characterize, and assess the antimicrobial activity and cytotoxicity of polymer blends based on chitosan (CT) and fish collagen (COL) produced by different precipitation methods. Polymer blends were obtained in alkaline (NaOH), saline (NaCl), and alkaline/saline (NaOH/NaCl) solutions with different CT:COL concentration ratios (20:80, 50:50, and 80:20). The polymer blends were characterized by various physicochemical methods and subsequently evaluated in terms of their in vitro antimicrobial and cytotoxicity activity. In this study, the degree of chitosan deacetylation was 82%. The total hydroxyproline and collagen content in the fish matrix was 47.56 mg. g-1 and 394.75 mg. g-1, respectively. The highest yield was 44% and was obtained for a CT:COL (80:20) blend prepared by precipitation in NaOH. High concentrations of hydroxyproline and collagen in the blends were observed when NaOH precipitation was used. Microbiological analysis revealed that the strains used in this work were sensitive to the biomaterial; this sensitivity was dose-dependent and increased with increasing chitosan concentration in the products. The biocompatibility test showed that the blends did not reduce the viability of fibroblast cells after 48 h of culture. An analysis of the microbiological activity of the all-polymer blends showed a decrease in the values of minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) for S. aureus and P. aeruginosa. The blends showed biocompatibility with NIH-3T3 murine fibroblast cells and demonstrated their potential for use in biomedical applications such as wound healing, implants, and scaffolds.

Ethyl Acetate Fraction of Bixa orellana and Its Component Ellagic Acid Exert Antibacterial and Anti-Inflammatory Properties against Mycobacterium abscessus subsp. massiliense.

Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.

Carvacrol reduces blood pressure, arterial responsiveness and increases expression of MAS receptors in spontaneously hypertensive rats.

AIM: To analyze the effect of the use of carvacrol in the cardiovascular system of spontaneously hypertensive rats (SHR). METHODS: Methods: Twenty animals were allocated in four groups, one group control Wistar receiving only sorbitol, used as vehicle of administration of the carvacrol (Wistar-Vehicle), one control group SHR, also receive only sorbitol (SHR-Vehicle), a third, treated with losartan (SHR-Losartan/50 mg/kg), and the fourth, treated with carvacrol (SHR - Carvacrol/20 mg/kg). Sorbitol, losartan and carvacrol were administered by oral gavage daily for 30-day. Hemodynamic variables, vascular reactivity, biochemical parameters, and expression of Mas and AT1 receptors in kidney tissues were analyzed. RESULTS: SHR- Carvacrol group showed a maximal effect of inhibition of 56% in the curve of norepinephrine. The Emax of the curves with Ca2+ were smaller in the groups SHR-losartan (40.17%) and SHR-carvacrol (35.71%) when compared to the SHR-Vehicle. The carvacrol increased the expression of the MAS receptors in kidney tissue. CONCLUSION: Thirty days of treatment with carvacrol showed an antihypertensive effect associated with less peripheral vascular resistance. Also, treatment with carvacrol increased the expression of MAS receptors in kidney tissue.

Modulação Autonômica Cardíaca é Fator Chave para Pressão Alta em Adolescentes / Cardiac Autonomic Modulation is a Key Factor for High Blood Pressure in Adolescentes

Resumo Fundamento O interesse pela hipertensão em crianças e adolescentes aumentou desde a atualização do sistema de classificação da pressão arterial para comparar com o sistema de classificação dos adultos, alterando a terminologia de "normal alta" para "pré-hipertensão". Objetivo O objetivo deste estudo foi analisar a associação da modulação autonômica cardíaca com os níveis pressóricos dos adolescentes. Métodos 203 adolescentes foram agrupados de acordo com a pressão arterial sistólica (PAS) e a pressão arterial diastólica (PAD). Um grupo foi caracterizado como pré-hipertensão, e o outro como normotenso. Foram coletadas características antropométricas, cardiovasculares e de qualidade do sono. Inicialmente, os dados foram submetidos ao teste de normalidade Kolmogorov-Smirnov . As variáveis quantitativas contínuas foram analisadas por meio do teste T de Student não pareado. Para análise das variáveis categóricas, foi utilizado o teste qui-quadrado. Um modelo de regressão logística foi realizado. O nível de significância estabelecido foi p<0,05. Os dados foram expressos como média ± desvio padrão e intervalo de confiança. O software R foi utilizado para análise dos dados. O tamanho do efeito foi calculado com a fórmula de Cohen. Resultados O grupo pré-hipertensão apresentou aumento da entropia de Shannon e diminuição da variância total. Além disso, no modelo de regressão logística, os adolescentes deste grupo tiveram 1,03 mais chances de ter a entropia de Shannon afetada quando a PAS foi ajustada ao gênero, maturação sexual, tempo escolar, idade, circunferência da cintura e qualidade do sono. Conclusão Nossos dados mostram que a modulação autonômica pode desempenhar um papel importante no desenvolvimento da pressão arterial elevada em adolescentes ao controlar fatores como tempo escolar e qualidade do sono.

Abstract Background The interest regarding hypertension among children and adolescents has increased since the blood pressure rating system was updated to be compared with the adult rating system, changing the terminology from "normal high" to "prehypertension". Objective This study aimed to analyze the association between cardiac autonomic modulation and pressure levels of adolescents. Methods 203 adolescents were grouped according to systolic blood pressure (SBP) and diastolic blood pressure (DBP). One group was characterized as prehypertension, and the other as normotensive. Anthropometric, cardiovascular and sleep quality characteristics were collected. Initially, the data were submitted to the Kolmogorov-Smirnov normality test. Continuous quantitative variables were analyzed using the unpaired Student t-test. For the analysis of categorical variables, a chi-square test was used. A logistic regression model was performed. The level of significance was set at p<0.05. The data were expressed as mean ± standard deviation and confidence interval. The R software was used for data analysis. The effect size was calculated using the Cohen's formula. Results The prehypertension group showed an increase in Shannon entropy and a decrease in total variance. Also, in the logistic regression model, adolescents in this group were 1.03 times more likely to have Shannon entropy's affected when SBP was adjusted for gender, sexual maturation, school time, age, waist circumference, and sleep quality. Conclusion Our data show that autonomic modulation may play an important role in the development of elevated blood pressure in adolescents, when controlling for other factors, such as school time and sleep quality.

Cardiac Autonomic Modulation is a Key Factor for High Blood Pressure in Adolescentes. / Modulação Autonômica Cardíaca é Fator Chave para Pressão Alta em Adolescentes.

BACKGROUND: The interest regarding hypertension among children and adolescents has increased since the blood pressure rating system was updated to be compared with the adult rating system, changing the terminology from "normal high" to "prehypertension". OBJECTIVE: This study aimed to analyze the association between cardiac autonomic modulation and pressure levels of adolescents. METHODS: 203 adolescents were grouped according to systolic blood pressure (SBP) and diastolic blood pressure (DBP). One group was characterized as prehypertension, and the other as normotensive. Anthropometric, cardiovascular and sleep quality characteristics were collected. Initially, the data were submitted to the Kolmogorov-Smirnov normality test. Continuous quantitative variables were analyzed using the unpaired Student t-test. For the analysis of categorical variables, a chi-square test was used. A logistic regression model was performed. The level of significance was set at p<0.05. The data were expressed as mean ± standard deviation and confidence interval. The R software was used for data analysis. The effect size was calculated using the Cohen's formula. RESULTS: The prehypertension group showed an increase in Shannon entropy and a decrease in total variance. Also, in the logistic regression model, adolescents in this group were 1.03 times more likely to have Shannon entropy's affected when SBP was adjusted for gender, sexual maturation, school time, age, waist circumference, and sleep quality. CONCLUSION: Our data show that autonomic modulation may play an important role in the development of elevated blood pressure in adolescents, when controlling for other factors, such as school time and sleep quality.

FUNDAMENTO: O interesse pela hipertensão em crianças e adolescentes aumentou desde a atualização do sistema de classificação da pressão arterial para comparar com o sistema de classificação dos adultos, alterando a terminologia de "normal alta" para "pré-hipertensão". OBJETIVO: O objetivo deste estudo foi analisar a associação da modulação autonômica cardíaca com os níveis pressóricos dos adolescentes. MÉTODOS: 203 adolescentes foram agrupados de acordo com a pressão arterial sistólica (PAS) e a pressão arterial diastólica (PAD). Um grupo foi caracterizado como pré-hipertensão, e o outro como normotenso. Foram coletadas características antropométricas, cardiovasculares e de qualidade do sono. Inicialmente, os dados foram submetidos ao teste de normalidade Kolmogorov-Smirnov . As variáveis quantitativas contínuas foram analisadas por meio do teste T de Student não pareado. Para análise das variáveis categóricas, foi utilizado o teste qui-quadrado. Um modelo de regressão logística foi realizado. O nível de significância estabelecido foi p<0,05. Os dados foram expressos como média ± desvio padrão e intervalo de confiança. O software R foi utilizado para análise dos dados. O tamanho do efeito foi calculado com a fórmula de Cohen. RESULTADOS: O grupo pré-hipertensão apresentou aumento da entropia de Shannon e diminuição da variância total. Além disso, no modelo de regressão logística, os adolescentes deste grupo tiveram 1,03 mais chances de ter a entropia de Shannon afetada quando a PAS foi ajustada ao gênero, maturação sexual, tempo escolar, idade, circunferência da cintura e qualidade do sono. CONCLUSÃO: Nossos dados mostram que a modulação autonômica pode desempenhar um papel importante no desenvolvimento da pressão arterial elevada em adolescentes ao controlar fatores como tempo escolar e qualidade do sono.

Effect of treatment with carvacrol and aerobic training on cardiovascular function in spontaneously hypertensive rats.

NEW FINDINGS: What is the central question of this study? Can two non-drug therapies, carvacrol and aerobic physical training, together have additive effects on the reduction of cardiovascular risks and control of arterial hypertension? What is the main finding and its importance? The oral use of carvacrol (20 mg/kg/day) can control sustained hypertension in spontaneously hypertensive rats, and when this use is associated with aerobic physical training, there is a more pronounced effect on the reduction of blood pressure values, making these therapies an adjunct option in the drug treatment of hypertension. ABSTRACT: Systemic arterial hypertension is considered the foremost cardiovascular risk factor, and it is important to examine different therapies that help prevent and treat it, especially when associated with other cardiovascular risk factors. In this context, it is known that both carvacrol and aerobic physical training benefit the cardiovascular system. This study investigated the effects of treatment with carvacrol combined with aerobic exercise on hypertensive rats with cardiovascular risk parameters. We used an experimental design with six groups: normotensive control (Wistar rats); hypertensive control (spontaneously hypertensive rats, SHR); positive control rats treated with amlodipine (Aml-20 mg); rats treated with carvacrol (Carv-20 mg); rats trained with exercise (Exer); and rats treated with carvacrol and exercise (ExerCarv). The treatment lasted for 4 weeks, monitoring heart rate and systolic blood pressure (SBP). At the end of the treatment, vascular reactivity tests were performed in addition to biochemical measurements of urea, creatinine, aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, atherogenic indexes, relative heart weight and histopathological analysis of cardiac perivascular tissue. Significant reductions in SBP were observed after the training period, with the ExerCarv group showing a greater magnitude of reduction (∆SBP = 88 ± 10.0 mmHg, 42%). This group also experienced reductions in atherogenic indices and improvement in all analysed lipid parameters, with no differences observed in the Exer group. The findings indicated that the interaction between aerobic exercise and carvacrol offers a greater BP reduction. Exercise is particularly effective for controlling biochemical parameters of cardiovascular risk, regardless of carvacrol use.

Inspiratory muscle training improves autonomic modulation and exercise tolerance in chronic obstructive pulmonary disease subjects: A randomized-controlled trial.

OBJECTIVES: We aimed to evaluate the effect a regular inspiratory muscle training program on autonomic modulation measured by heart rate variability, exercise capacity and respiratory function in chronic obstructive pulmonary disease subjects (COPD). DESIGN: Single-center controlled study, with balanced randomization (1:1 for two arms). SETTING: A COPD reference hospital localized in Sao Luís, Brazil. PARTICIPANTS: 22 COPD subjects joined the study. INTERVENTIONS: Three times a week for four weeks inspiratory muscle training (IMT) at 30% of PImax. MAIN OUTCOME MEASURES: Pulmonary capacities and inspiratory pressure, total six-minute walk test and, cardiac autonomic modulation. RESULTS: The intervention group showed improvements in the cardiac autonomic modulation, with increased vagal modulation (total variability and HF [ms2; adjusted p < 0.05]); increased expiratory and inspiratory capacities and, increased distance in the 6-min walk test. CONCLUSION: 12 weeks of IMT at 30% of the maximal inspiratory pressure increased cardiac autonomic modulation, expiratory and inspiratory and exercise capacity in COPD subjects.

A Case-control Study of Exercise and Kidney Disease: Hemodialysis and Transplantation.

We aimed to analyze the effect of an exercise training program in autonomic modulation, and exercise tolerance of hemodialysis and kidney-transplanted patients. 4 groups of exercised and non-exercised patients undergoing hemodialysis and kidney-transplanted subjects had their biochemical tests, and heart rate variability evaluations analyzed. Also, sleep quality, anxiety and depression questionnaires were evaluated. Both exercised groups showed improvements in cardiovascular autonomic modulation, biochemical markers, and exercise tolerance after the exercise training program. The exercised kidney-transplanted patients group showed better improvements in cardiovascular autonomic modulation, biochemical markers, and exercise tolerance when compared to the exercised hemodialysis patients group. Both groups showed improvements in sleep quality, anxiety, and depression. The group of kidney-transplanted patients show better results in the cardiovascular autonomic modulation than subjects undergoing hemodialysis. However, the patients undergoing hemodialysis showed improvements in blood pressure, HDL, hemoglobin and phosphorus, changes not observed in the kidney-transplanted group. Exercise is beneficial for both hemodialysis and kidney-transplanted patients groups. However, exercise programs should be focused mainly in improving cardiovascular risk factors in the HD patients.

Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats.

This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.