Development, characterization and antioxidant activity of polysorbate based O/W emulsion containing polyphenols derived from Hippophae rhamnoides and Cassia fistula

The objective of this study was to develop a pharmaceutical O/W emulsion containing plant-derived polyphenol extracts and evaluate its stability and antioxidant activity. O/W emulsions were prepared using ionic surfactant polysorbate 80 (Tween 80®). The odorwas adjusted with few drops of blue sea fragrance. DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was used to evaluate the antioxidant activity of the plant extracts alone and emulsions containing these extracts. Physical stability was assessed by submitting the emulsions to storage at 8 ºC, 25 ºC, 40 ºC and 40 ºC + 70% RH (relative humidity) for two months. Various physical characteristics of emulsions monitored, include color, creaming, liquefaction, centrifugation and pH. Brookfield rotational rheometer was used to determined viscosities and rheological behavior of emulsions. Different types of emulsion were determined microscopically, while pH values of emulsions were measured by a pH meter. Electrical conductivity data confirmed that the outer phase was water. Samples presented an acceptable pH value for an external topical use. Shear thinning behaviour was observed for all emulsions. The polyphenol-rich-plant-derived extracts alone and the extract containing emulsions showed good antioxidant activities. This research confirmed that the method used was suitable for preparing emulsions with Hippophae rhamnoids and Cassia fistula extracts, suggesting that those emulsions are suitable for topical use.O presente estudo objetivou o desenvolvimento de uma emulsão farmacêutica óleo-água contendo extratos de plantas ricos em polifenóis, a comparação à sua formulação-controle e a avaliação de sua estabilidade, assim como de sua capacidade antioxidante. Extrato concentrado de Hippophae rhamnoids e Cassia fistula foi encapsulado no interior da fase oleosa da emulsão O/W. As emulsões foram preparadas usando o tensoativo iônico monooleato sorbital de polioxietileno (Tween 80®). O odor foi ajustado pela adição de algumas gotas de fragrância azul do mar. O ensaio do DPPH (1,1-difenil-2-picrilidrazil) foi utilizado para avaliar a atividade antioxidante dos extratos de plantas sozinhos e nas emulsões contendo os extratos. A estabilidade física foi avaliada submetendo os cremes a diferentes temperaturas de estocagem, como a 8 ºC, 25 ºC e 40 ºC e a 40% + 70% de umidade relativa por um período de 2 meses. As características físicas das emulsões foram monitoradas por 2 meses incluindo cor, cremosidade, liquefação, centrifugação e pH. O reômetro rotacional de Brookfield foi utilizado para determinar a viscosidade e o comportamento reológico das emulsões. O programa Rheocalc Brookfield foi utilizado para análise dos dados. As características organolépticas também foram avaliadas. O tipo de emulsão foi determinado microscopicamente, enquanto o pH das emulsões foi avaliado por meio de um pHmetro. A estabilidade farmacêutica esperada das emulsões foi alcançada dentro dos dois meses de estudo. Os resultados da condutividade elétrica confirmaram que a fase externa da emulsão era composta de água. O pH das amostras estava dentro da normalidade para uso tópico. A emulsão apresentou boa fragrância e pode ser retirada da pele com água após a aplicação, características desejáveis em emulsões O/W. Os extratos vegetais ricos em polifenóis isolados ou nas emulsões apresentaram boa atividade antioxidante. Nossos estudos confirmaram que o método utilizado foi adequado para preparar a emulsão semi-sólida contendo extratos de Hippophae rhamnoids e Cassia fistula. Nossos achados sugerem que emulsões contendo extratos de Hippophae rhamnoids e Cassia fistula são adequados para o uso tópico

FisioArte - estudando fisiologia através da releitura das obras de arte de Tarsila do Amaral: PhysioArt - studying physiology through Tarsila do Amaral artwork reinterpretations

Diferentes estudos têm mostrado que a introdução da arte em disciplinas de ciências biológicas têm sido uma importante ferramenta pedagógica, estimulando a criatividade, sensibilidade e o desenvolvimento do raciocínio lógico dos discentes. Nós desenvolvemos um projeto pedagógico denominado FisioArte, o qual propõe a interação entre fisiologia e arte como estratégia de ensino e aprendizagem. Para tanto, realizamos com os discentes, reinterpretações de obras de arte imprimindo os conceitos fisiológicos estudados em sala de aula. Em uma das atividades da FisioArte, sob a temática da fisiologia da glândula adrenal foi sugerido aos discentes que fizessem a releitura das obras da artista brasileira, Tarsila do Amaral. O presente relato de experiência descreve uma edição da FisioArte com os alunos do curso de bacharelado em biotecnologia da Universidade Federal da Paraíba, na disciplina de fisiologia humana. Para tanto, aqui apresentamos as releituras das obras: “O ovo (urutu)”, “A boneca”, “Estrada de ferro central do brasil”, “Operários”, “A negra” e “Estudo (La Tasse) no contexto da fisiologia da glândula adrenal. Essa atividade, a FisioArte, mostrou-se eficiente para motivar os alunos, bem como despertar o interesse pelo estudo da fisiologia

Warifteine therapeutic treatment reduced leukocyte recruitment and anxiety-like response in ovalbumin-induced allergic pulmonary inflammation / Tratamento terapêutico com warifteína reduz recrutamento de leucócitos e resposta semelhante á ansiedade na inflamação pulmonar alérgica induzida por ovalbumina

Pulmonary inflammation plays a fundamental role in the pathophysiology of allergic asthma, which is characterized by lower airway obstruction, bronchial hyperresponsiveness, tissue remodeling, recruitment of inflammatory cells, with a predominance of eosinophils, in addition to behavioral disorders such as anxiety. The aim of this study was to evaluate the therapeutic effect of the alkaloid warifteine, from the medicinal plant Cissampelos sympodialis, on anxiety-like behavior, respiratory frequency and leukocyte recruitment in an experimental model of allergic pulmonary inflammation. Swiss female mice were sensitized and challenged with ovalbumin (OVA) throughout the experimental protocol. The animals were treated orally with warifteine (2 mg / kg), subcutaneously with dexamethasone (2 mg / kg) or intraperitoneally with diazepam (1 mg / kg), 1 h after the OVA-challenges. On the last day of the antigenic challenge, the mice were tested for behavior using the Elevated Plus Maze (EPM) and for respiratory rate using full body plethysmography. The following day, the mice were euthanized to collect the bronchoalveolar lavage fluid (BALF) and leukocyte count. The data obtained showed that OVA-sensitization induced a behavior similar to anxiety in mice since the EPM test showed that the OVA group increased the number of entries and the time spent in the closed arms (CA) of the apparatus and reduced these parameters in the open arms (OA) compared to the Salina group. Warifteine treatment reversed both parameters analyzed, increasing the time spent (p <0.0001) and number of entries (p <0.01) in OA, decreasing the time spent (p <0.01) and number of entries (p <0.0001) in the CA, similarly to dexamethasone and diazepam standard drugs. Warifteine also reduced the respiratory rate (p <0.01) compared to the OVA group. The behavioral and breathing changes of the tested animals showed a relationship with the increase in the total and differential inflammatory leukocyte number in the OVA group compared to the Saline group. Therapeutic treatment with warifteine decreased the inflammatory process, reducing the number of total cells (p <0.0001) dependent of eosinophils and neutrophils numbers (p <0.001), as well as the percentage of eosinophils (p <0.0001). These data show that therapeutic treatment with warifteine is able to inhibit anxiety-like behavior and respiratory rate, due to a mechanism related to the inhibition of eosinophilic migration in an experimental model of allergic pulmonary inflammation.Pulmonary inflammation plays a fundamental role in the pathophysiology of allergic asthma, which is characterized by lower airway obstruction, bronchial hyperresponsiveness, tissue remodeling, recruitment of inflammatory cells, with a predominance of eosinophils, in addition to behavioral disorders such as anxiety. The aim of this study was to evaluate the therapeutic effect of the alkaloid warifteine, from the medicinal plant Cissampelos sympodialis, on anxiety-like behavior, respiratory frequency and leukocyte recruitment in an experimental model of allergic pulmonary inflammation. Swiss female mice were sensitized and challenged with ovalbumin (OVA) throughout the experimental protocol. The animals were treated orally with warifteine (2 mg / kg), subcutaneously with dexamethasone (2 mg / kg) or intraperitoneally with diazepam (1 mg / kg), 1 h after the OVA-challenges. On the last day of the antigenic challenge, the mice were tested for behavior using the Elevated Plus Maze (EPM) and for respiratory rate using full body plethysmography. The following day, the mice were euthanized to collect the bronchoalveolar lavage fluid (BALF) and leukocyte count. The data obtained showed that OVA-sensitization induced a behavior similar to anxiety in mice since the EPM test showed that the OVA group increased the number of entries and the time spent in the closed arms (CA) of the apparatus and reduced these parameters in the open arms (OA) compared to the Salina group. Warifteine treatment reversed both parameters analyzed, increasing the time spent (p <0.0001) and number of entries (p <0.01) in OA, decreasing the time spent (p <0.01) and number of entries (p <0.0001) in the CA, similarly to dexamethasone and diazepam standard drugs. Warifteine also reduced the respiratory rate (p <0.01) compared to the OVA group. The behavioral and breathing changes of the tested animals showed a relationship with the increase in the total and differential inflammatory leukocyte number in the OVA group compared to the Saline group. Therapeutic treatment with warifteine decreased the inflammatory process, reducing the number of total cells (p <0.0001) dependent of eosinophils and neutrophils numbers (p <0.001), as well as the percentage of eosinophils (p <0.0001). These data show that therapeutic treatment with warifteine is able to inhibit anxiety-like behavior and respiratory rate, due to a mechanism related to the inhibition of eosinophilic migration in an experimental model of allergic pulmonary inflammation

SYNTHESIS, IN SILICO CHARACTERIZATION AND EX VIVO EVALUATION OF THE NOVEL ORGANIC NITRATE NDIBP AS A POTENTIAL VASORELAXANT AGENT

Objective: This study aimed to describe the synthesis and biological/pharmacokinetic potential of the 1,3-diisobutoxypropan-2-yl nitrate (NDIBP) using in silico and ex vivo approaches. Methods: The compound was characterized by Fourier-transform infrared spectroscopy and 1H and 13C- nuclear magnetic resonance spectra. NDIBP biological activity spectrum was obtained by Prediction of Activity Spectra for Substances (PASS). The pharmacological effect was validated in ex vivo studies using mesenteric artery. Drug-like properties and Absorption Distribution Metabolism Excretion and Toxicity (ADMET) studies were carried out by pkCSM (Predicting Small-Molecule Pharmacokinetic Properties Using Graph-Based Signatures) software. Results: PASS prediction indicated NDIBP as nitric oxide (NO) donor with vasodilator effect. Ex vivo studies validated PASS analysis and showed the NDIBP vasorelaxant activity in mesenteric arteries. Physicochemical parameters and ADMET prediction suggested that NDIBP is a drug-like molecule with a good theoretical oral bioavailability, good absorption in the gastrointestinal tract, and a low distribution in the tissues. Conclusion: All the data indicated that NDIBP possesses biological activities and drug-like properties to be considered as a vasorelaxant agent and a good candidate for further investigation in the treatment of arterial hypertension and drug development studies

Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats.

Baroreceptor reflex is an important system for neural control of blood pressure. Recently, reactive oxygen species (ROS) have been shown to play an important role in neuronal activity of central areas related to blood pressure control. The aim of this study was to investigate the effects elicited by ascorbic acid (AAC) and N-acetylcysteine (NAC) injections into the 4thV on the parasympathetic component of the baroreflex. Male Wistar rats were implanted with a stainless steel guide cannula into the 4thV. One day prior to the experiments, the femoral artery and vein were cannulated for pulsatile arterial pressure, mean arterial pressure and heart rate measurements and drug administration, respectively. After baseline recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 3_g/kg, i.v.) and a depressor dose of sodium nitroprusside (SNP, 30_g/kg, i.v.) before (control) and 5, 15, 30 and 60 min after AACorNACinto the 4thV. ControlPHEinjection induced baroreflex-mediated bradycardia (?93?13 bpm, n = 7). Interestingly, after AAC injection into the 4thV, PHE injection produced a transient tachycardia at 5 (40?23 bpm), 15 (26?22 bpm) and 30 min (59?21 bpm). No changes were observed in baroreflexmediated tachycardia evoked by SNP after AAC injection on 4thV (control: 151?23bpm vs. 135?18bpm at 5 min after AAC, n = 7). In the NAC treated group, PHE induced a reduction in reflex bradycardia at 5 min when compared to control (?11?17bpm vs. ?83?15 bpm, n = 7). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after NAC injection on 4thV. The antioxidants AAC and NAC may act in the central nervous system affecting the parasympathetic component of the cardiac baroreflex

Secondary Metabolites from Sida rhombifolia L. (Malvaceae) and the Vasorelaxant Activity of Cryptolepinone

The phytochemical study of Sida rhombifolia L. (Malvaceae) led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a) and stigmasterol (1b), sitosterol-3-O-b-D-glucopyranoside (2a) and stigmasterol-3-O-b-D-glucopyranoside (2b), phaeophytin A (3), 173-ethoxypheophorbide A (4), 132-hydroxy phaeophytin B (5), 173-ethoxypheophorbide B (6), 5,7-dihydroxy-4'-methoxyflavone (7), cryptolepinone (8) and a salt of cryptolepine (9). Their structures were identified by 1H- and 13C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time

Alkaloids and Phenolic Compounds from Sida rhombifolia L. (Malvaceae) and Vasorelaxant Activity of Two Indoquinoline Alkaloids

The follow-up of phytochemical and pharmacological studies of Sida rhombifolia L. (Malvaceae) aims to strengthen the chemosystematics and pharmacology of Sida genera and support the ethnopharmacological use of this species as hypotensive herb. The present work reports phytoconstituents isolated and identified from aerial parts of S. rhombifolia by using chromatographic and spectroscopic methods. The study led to the isolation of scopoletin (1), scoporone (2), ethoxy-ferulate (3), kaempferol (4), kaempferol-3-O-β-d-glycosyl-6′′-α-d-rhamnose (5), quindolinone (6), 11-methoxy-quindoline (7), quindoline (8), and the cryptolepine salt (9). The alkaloids quindolinone (6) and cryptolepine salt (9) showed vasorelaxant activity in rodent isolated mesenteric arteries

Antioxidant and Antihypertensive Effects of a Chemically Defined Fraction of Syrah Red Wine on Spontaneously Hypertensive Rats

A particularly phenolic-rich fraction extracted from red wine from the São Francisco valley (Northeastern Brazil) was chemically characterized and its hypotensive and antioxidant effects on spontaneously hypertensive rats were studied both in vitro and in vivo. The liquid-liquid pH dependent fractionation scheme afforded a fraction with high content of bioactive phenolics such as flavonols, flavonol glycosides, phenolic acids and anthocyanins, whose identities were confirmed by liquid chromatography coupled to mass spectrometry analysis. Pretreatment of spontaneously hypertensive rats with this wine fraction at doses of 50 and 100 mg/kg by gavage. for 15 days was able to decrease mean arterial pressure and heart rate as well as decrease serum lipid peroxidation. The fraction at concentrations of 0.01–1000 µg/mL induced concentration-dependent relaxation of isolated rat superior mesenteric artery rings pre-contracted with phenylephrine and this effect was not attenuated by endothelium removal. Our results demonstrate it is possible for phenolic constituents of red wine that are orally bioavailable to exert in vivo hypotensive and antioxidant effects on intact endothelial function

Effect of maternal dyslipidaemia on the cardiorespiratory physiology and biochemical parameters in male rat offspring

International audienceThe present study evaluated the effects of maternal dyslipidaemia on blood pressure (BP), cardiorespiratory physiology and biochemical parameters in male offspring. Wistar rat dams were fed either a control (CTL) or a dyslipidaemic (DLP) diet during pregnancy and lactation. After weaning, both CTL and DLP offspring received standard diet. On the 30th and 90th day of life, blood samples were collected for metabolic analyses. Direct measurements of BP, respiratory frequency (RF), tidal volume (VT) and ventilation (VE) under baseline condition, as well as during hypercapnia (7 % CO2) and hypoxia (KCN, 0·04 %), were recorded from awake 90-d-old male offspring. DLP dams exhibited raised serum levels of total cholesterol (TC) (4·0-fold), TAG (2·0-fold), VLDL+LDL (7·7-fold) and reduced HDL-cholesterol (2·4-fold), insulin resistance and hepatic steatosis at the end of lactation. At 30 d of age, the DLP offspring showed an increase in the serum levels of TC (P<0·05) and VLDL+LDL (P<0·05) in comparison with CTL offspring. At 90 d of age, DLP offspring exhibited higher mean arterial pressure (MAP, approximately 34 %). In the spectral analysis, the DLP group showed augmented low-frequency (LF) power and LF:high-frequency (HF) ratio when compared with CTL offspring. In addition, the DLP animals showed a larger delta variation in arterial pressure after administration of the ganglionic blocker (P=0·0003). We also found that cardiorespiratory response to hypercapnia and hypoxia was augmented in DLP offspring. In conclusion, the present data show that maternal dyslipidaemia alters cardiorespiratory physiology and may be a predisposing factor for hypertension at adulthood

Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life

International audienceBackground and aim: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum(WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring.Methods and results: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receivingL. plantarum WJL during pregnancy and lactation (DLP-Lp(WJL)).L. plantarum WJL (1 x 10(9)CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-Lp(WJL) dams had reduced blood pressure and recovered vascular function in later life.Conclusion: Administration ofL. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring