Kely de Picoli Souza

Long term treatment with ACE inhibitor enalapril decreases body weight gain and increases life span in rats.

Renin-angiotensin system is involved in homeostasis processes linked to renal and cardiovascular system and recently has been linked to metabolic syndrome. We analyzed the influence of long term angiotensin I converting enzyme (ACE) inhibitor enalapril treatment in normotensive adult Wistar rats fed with standard or palatable hyperlipidic diets. Our results show that long term enalapril treatment decreases absolute food intake, serum leptin concentration and body weight gain. Moreover, in adipose tissue, enalapril treatment led to decreased ACE activity, enhanced the expression of peroxisome proliferator activated receptor gamma, adiponectin, hormone-sensitive lipase, fatty acid synthase, catalase and superoxide dismutase resulting in prolonged life span. On the other hand, the ACE inhibitor was not able to improve the transport of leptin through the blood brain barrier or to alter the sensitivity of this hormone in the central nervous system. The effect of enalapril in decreasing body weight gain was also observed in older rats. In summary, these results extend our previous findings and corroborate data from the literature regarding the beneficial metabolic effects of enalapril and show for the first time that this ACE inhibitor prolongs life span in rats also fed with palatable hyperlipidic diet, an action probably correlated with adipose tissue metabolic modulation and body weight reduction.

Antimicrobial, antioxidant and cytotoxic activities of propolis from Melipona orbignyi (Hymenoptera, Apidae)

Propolis from stingless bees is well known for its biologic properties; however, few studies have demonstrated these effects. Therefore, this study aimed to investigate the chemical composition and antimicrobial, antioxidant and cytotoxic activities of propolis from the stingless bee Melipona orbignyi, found in Mato Grosso do Sul, Brazil. The chemical composition of the ethanol extract of propolis (EEP) indicated the presence of aromatic acids, phenolic compounds, alcohols, terpenes and sugars. The EEP was active against the bacterium Staphylococcus aureus and the fungus Candida albicans. The EEP showed antioxidant activity by scavenging free radicals and inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent. Additionally, EEP promoted cytotoxic activity and primarily necrotic death in K562 erythroleukemia cells. Taken together, these results indicate that propolis from M. orbignyi has therapeutic potential for the treatment and/or prevention of diseases related to microorganism activity, oxidative stress and tumor cell proliferation.

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in anti-hypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases.

Antioxidant and Antihyperlipidemic Effects of Campomanesia adamantium O. Berg Root

Campomanesia adamantium O. Berg, popularly known as guavira, has been used in Brazilian traditional medicine for reduction of serum lipid. The present study was carried out to investigate the antioxidant and antihyperlipidemic effects of Campomanesia adamantium root aqueous extract (ExCA). Phenolic compounds were quantified in the ExCA and gallic and ellagic acids were identified by HPLC. ExCA showed efficiency in 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, with IC50 similar to butylhydroxytoluene control, and protected the erythrocytes against lipid peroxidation induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride, reducing generated malondialdehyde. Hyperlipidemic Wistar rats treated daily by gavage during eight weeks with ExCA (200 mg/kg of body weight) showed reduced serum level of total cholesterol and triglycerides, similar to normolipidemic rats and hyperlipidemic rats treated with simvastatin (30 mg/kg of body weight) and ciprofibrate (2 mg/kg of body weight). Moreover, the treatment with ExCA also decreased malondialdehyde serum level in the hyperlipidemic rats. The body weight and organ mass were unmodified by ExCA in hyperlipidemic rats, except an increase of liver mass; however, the hepatic enzymes, alanine aminotransferase and aspartate aminotransferase, were unchanged. Together, these results confirm the potential value of Campomanesia adamantium root for lowering lipid peroxidation and lipid serum level, improving risk factors for cardiometabolic diseases development.

Antimicrobial, Antioxidant, Anti-Inflammatory, and Cytotoxic Activities of Propolis from the Stingless Bee Tetragonisca fiebrigi (Jataí)

Propolis from stingless bees Tetragonisca fiebrigi found in Brazil is used in folk medicine by their nutritional and therapeutic properties. However, there are no scientific records evidencing such properties. The present study was designed to investigate the chemical composition and the biological properties of propolis from T. fiebrigi. For this, the chemical composition of the ethanol extract of propolis (EEP) was determined by GC-MS and presented phenolic compounds, alcohol, and terpenes as its major class compounds. The antimicrobial activity was accessed in gram-positive and gram-negative bacteria and in fungi, isolated from different biological fluids and reference strains. The EEP was active against all microorganisms and showed antioxidant activity by scavenging free radicals, inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent. The anti-inflammatory potential of the EEP was confirmed by inhibition of the hyaluronidase enzyme. The cytotoxic activity was concentration-dependent against K562 cells, with a predominance of death by necrosis. Taken together, these results show that propolis from T. fiebrigi has important therapeutic activities, which suggest its potential application in the pharmaceutical industry, as well as in health foods, beverages, and nutritional supplements.

Antioxidant and Cytotoxic Activity of Hydroethanolic Extract from Jacaranda decurrens Leaves

Background and Purpose Leaves of Jacaranda decurrens are used in traditional Brazilian medicine to treat metabolic diseases related to increased reactive oxygen species. The present study evaluated the antioxidant and cytotoxic potential of hydroethanolic extract from the leaves of Jacaranda decurrens subsp. symmetrifoliolata. Experimental Approach Phenolic compounds, flavonoids and saponins were evaluated in an ethanol∶water (80∶20, v/v) extract from the leaves of Jacaranda decurrens subsp. symmetrifoliolata (E-Jds). The antioxidant activity of E-Jds was investigated by assessing the following: 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity; protection against 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis of erythrocytes; in vitro and in vivo malondialdehyde dosage; and the ability to activate antioxidant enzymes. K562 leukemia cells were used for the cytotoxic evaluation of E-Jds and for the assessment of the cell death profile through flow cytometry. Key Results Phenolic and flavonoid compounds were quantified as 14.38% and 2.15%, respectively, of E-Jds. These phenolic and flavonoid compounds proved to be able to scavenge DPPH free radicals with an IC50 of 9.3±3.3 µg/mL, to protect up to 50% of erythrocytes against AAPH-induced hemolysis and to reduce in vitro and in vivo malondialdehyde levels up to 84% and 22%, respectively. E-Jds also increased glutathione peroxidase enzyme activity, with a concomitant decrease in superoxide dismutase and catalase activity, and exhibited dose-dependent cytotoxic activity on K562 erythroleukemia cells with cell death occurring via both late apoptosis and necrosis. Conclusions E-Jds exhibits in vitro and in vivo antioxidant potential, which may be the mechanism mediating the metabolic activities reported in folk medicine. Furthermore, the cytotoxic activity identified in this study contributes with the knowledge of antiproliferative activities that have been described in the literature for the genus Jacaranda.

Functional assessment of angiotensin II and bradykinin analogues containing the paramagnetic amino acid TOAC

This study characterized pharmacologically the functional responses to agonists angiotensin II (AngII) and bradykinin (BK) derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin label at the N-terminal (TOAC1-AngII and TOAC0-BK) and internal (TOAC3-AngII and TOAC3-BK) positions of these vasoactive peptides. Affinity constants of the ligands for AT1 and B2 receptors were evaluated in vitro by binding assays and biological effects by extracellular acidification rates and in vivo by blood pressure responses. In contrast to internally labeled analogues (TOAC3-AngII or TOAC3-BK), the TOAC1-AngII and TOAC0-BK derivatives dose-dependently increased the extracellular acidification rate in adherent cultured Chinese hamster ovary (CHO) cells expressing AT1 or B2 receptors, respectively. In addition, TOAC(1)-AngII induced an increase in blood pressure when injected intravenously in awaken rats although with a potency four times smaller when compared to native AngII. Similarly to BK, TOAC0-BK dose-dependently decreased blood pressure when injected intra-arterially in rats with a lower potency when compared to the native peptide. On the contrary, TOAC3-AngII or TOAC3-BK did not provoke any alteration in blood pressure levels. In summary, our results confirmed that the insertion of TOAC-probe in the N-terminal region of peptides does not significantly modify the affinity or biological activity in vitro and in vivo conditions and could be an important tool to evaluate peptide-receptor interaction mechanism. Conversely, possibly due to the unique bend-inducing property of the cyclic TOAC probe, its insertion at position 3 in both AngII and BK structures seems to restrict the interaction and the activation of the AT1 and B2 receptors.

Antioxidant, Antimicrobial and Cytotoxic Properties as Well as the Phenolic Content of the Extract from Hancornia speciosa Gomes

Hancornia speciosa Gomes (Apocynaceae) is a fruit tree, popularly known as mangabeira, and it is widely distributed throughout Brazil. Several parts of the plant are used in folk medicine, and the leaf and bark extracts have anti-inflammatory, antihypertensive, antidiabetic, and antimicrobial properties. In this study, we investigated the chemical composition of the ethanolic extract of Hancornia speciosa leaves (EEHS) and its antioxidant, antimicrobial, and cytotoxic activities as well as the mechanisms involved in cell death. The chemical compounds were identified by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The antioxidant activity of the EEHS was investigated using the method that involves the scavenging of 2,2-diphenyl-1-picrylhydrazyl free radicals as well as the inhibition of oxidative hemolysis and lipid peroxidation induced by 2,2’-azobis (2-amidinopropane) in human erythrocytes. The antimicrobial activity was determined by calculating the minimum inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, and zone of inhibition. Kasumi-1 leukemic cells were used to assess the cytotoxic activity and mechanisms involved in cell death promoted by the EEHS. The chemical compounds identified were quinic acid, chlorogenic acid, catechin, rutin, isoquercitrin, kaempferol-rutinoside, and catechin-pentoside. The EEHS demonstrated antioxidant activity via the sequestration of free radicals, inhibition of hemolysis, and inhibition of lipid peroxidation in human erythrocytes incubated with an oxidizing agent. The antimicrobial activity was observed against American Type Culture Collection (ATCC) and hospital strains of bacteria and fungi, filamentous fungi and dermatophytes. The cytotoxic activity of the EEHS was induced by apoptosis, reduction of the mitochondrial membrane potential, and activation of cathepsins. Together, these results indicate the presence of phenolic compounds and flavonoids in the EEHS and that their antioxidant, antimicrobial, and cytotoxic activities in acute myeloid leukemia cells are mediated by apoptosis.

The Chemical Profile of Senna velutina Leaves and Their Antioxidant and Cytotoxic Effects.

Natural products can be a source of biomolecules with antioxidant activity which are able to prevent oxidative stress-induced diseases and show antitumor activity, making them important sources of new anticancer drug prototypes. In this context, this study aimed to analyze the chemical composition of an ethanol extract of Senna velutina leaves and to assess its antioxidant and cytotoxic activities in leukemic cells. The antioxidant properties were evaluated using a DPPH free radical scavenging assay and by examining the extracts inhibition of AAPH-induced lipid peroxidation in human erythrocytes. Its cytotoxicity and possible mechanisms of action were assessed in Jurkat and K562 leukemic cell lines. The ethanol extract contained flavonoids, such as epigallocatechin, epicatechin, kaempferol heteroside, rutin, and dimeric and trimeric proanthocyanidin derivatives. The extract exhibited antioxidant activity by scavenging free radicals and antihemolytic action, and it decreased malondialdehyde content in human erythrocytes. Furthermore, the extract also induced leukemic cell death by activating intracellular calcium and caspase-3, decreasing mitochondrial membrane potential, and arresting the cell cycle in S and G2 phases. Hence, S. velutina leaf extract contains antioxidant and antileukemic biomolecules with potential applications in diseases associated with oxidative stress and in the inhibition of tumor cell proliferation.

Antioxidant, Cytotoxic, and Toxic Activities of Propolis from Two Native Bees in Brazil: Scaptotrigona depilis and Melipona quadrifasciata anthidioides

Propolis is a natural mixture of compounds produced by various bee species, including stingless bees. This compound has been shown to exhibit antioxidant, antiproliferative, and antitumor activities. The present study aimed to determine the chemical constituents as well as the antioxidant, cytotoxic, and toxic activities of ethanol extracts of propolis obtained from the stingless bees Scaptotrigona depilis and Melipona quadrifasciata anthidioides, which are found in Brazil. Phytosterols, terpenes, phenolic compounds, and tocopherol were identified in the ethanol extracts of propolis (EEPs) in different concentrations. The compounds stigmasterol, taraxasterol, vanilic acid, caffeic acid, quercetin, luteolin, and apigenin were found only in EEP-M. The EEPs were able to scavenge the free radicals 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and protected human erythrocytes against lipid peroxidation, with the latter effect being demonstrated by their antihemolytic activity and inhibition of malondialdehyde formation. The EEPs showed cytotoxic activity against erythroleukemic cells and necrosis was the main mechanism of death observed. In addition, the concentrations at which the EEPs were cytotoxic were not toxic against Caenorhabditis elegans. In this context, it is concluded that EEP-S and EEP-M show antioxidant and cytotoxic activities and are promising bioactive mixtures for the control of diseases associated with oxidative stress and tumor cell proliferation.