Maria Goretti Rodrigues de Queiroz

Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet

Excess visceral adiposity may predispose to chronic diseases like hypertension and type 2 diabetes with a high risk for coronary artery disease. Adipose tissue secreted cytokines and oxidative stress play an important role in chronic disease progression. To combat adiposity, plant-derived triterpenes are currently receiving much attention as they possess antioxidant and anti-inflammatory properties and the ability to regulate glucose and lipid metabolism. In the search for potential antiobese compounds from natural sources, this study evaluated the effects of oleanolic acid (OA), a pentacyclic triterpene commonly present in fruits and vegetables, in glucose tolerance test and on high-fat diet (HFD)-induced obesity in mice. Adult male Swiss mice treated or not with OA (10 mg/kg) were fed a HFD during 15 weeks. Sibutramine (SIB) treated group (10 mg/kg) was included for comparison. Weekly body weights, food and water consumption were measured, and at the end of study period, the levels of blood glucose and lipids, plasma hormone levels of insulin, ghrelin and leptin, and the visceral abdominal fat content were analysed. Mice treated with OA and fed a HFD showed significantly (p<0.05) improved glucose tolerance, decreased body weights, visceral adiposity, blood glucose, plasma lipids relative to their respective controls fed no OA. Additionally, OA treatment, while significantly elevating the plasma hormone level of leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than lipase. Sibutramine-treated group also manifested similar effects like OA except for blood glucose level that was not different from HFD control. These findings suggest that OA ameliorates visceral adiposity and improves glucose tolerance in mice and thus has an antiobese potential through modulation of carbohydrate and fat metabolism.

Betulinic Acid, a Natural Pentacyclic Triterpenoid, Prevents Abdominal Fat Accumulation in Mice Fed a High-Fat Diet

In the search for potential antiobese agents from natural sources, this study investigated the effects of betulinic acid (BA), a pentacyclic triterpene from Clusia nemorosa L. (Clusiaceae), in mice on a high-fat diet (HFD). Adult male Swiss mice (n = 8) treated or not with BA (50 mg/L, in drinking water) were fed a HFD during 15 weeks. Mice treated with BA and fed a HFD showed significantly (P < 0.05) decreased body weights, abdominal fat accumulation, blood glucose, plasma triglycerides, and total cholesterol relative to their respective controls fed no BA. Additionally, BA treatment, while significantly elevating the plasma hormone levels of insulin and leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than the lipase. These findings suggest that BA has an antiobese potential through modulation of fat and carbohydrate metabolism, and it may be a suitable lead compound in the treatment of obesity.

Antibacterial and antiparasitic effects of Bothrops marajoensis venom and its fractions: Phospholipase A2 and l-amino acid oxidase

Some proteins present in snake venom possess enzymatic activities, such as phospholipase A(2) and l-amino acid oxidase. In this study, we verify the action of the Bothrops marajoensis venom (BmarTV), PLA(2) (BmarPLA(2)) and LAAO (BmarLAAO) on strains of bacteria, yeast, and Leishmania sp. The BmarTV was isolated by Protein Pack 5PW, and several fractions were obtained. Reverse phase HPLC showed that BmarPLA(2) was isolated from the venom, and N-terminal amino acid sequencing of sPLA(2) showed high amino acid identity with other lysine K49 sPLA(2)s isolated from Bothrops snakes. The BmarLAAO was purified to high molecular homogeneity and its N-terminal amino acid sequence demonstrated a high degree of amino acid conservation with others LAAOs. BmarLAAO was able to inhibit the growth of P. aeruginosa, C. albicans and S. aureus in a dose-dependent manner. The inhibitory effect was more significant on S. aureus, with a MIC=50 microg/mL and MLC=200 microg/mL. However, the BmarTV and BmarPLA(2) did not demonstrate inhibitory capacity. BmarLAAO was able to inhibit the growth of promastigote forms of L. chagasi and L. amazonensis, with an IC(50)=2.55 microg/mL and 2.86 microg/mL for L. amazonensis and L. chagasi, respectively. BmarTV also provided significant inhibition of parasitic growth, with an IC(50) of 86.56 microg/mL for L. amazonensis and 79.02 microg/mL for L. chagasi. BmarPLA(2) did not promote any inhibition of the growth of these parasites. The BmarLAAO and BmarTV presented low toxicity at the concentrations studied. In conclusion, whole venom as well as the l-amino acid oxidase from Bothrops marajoensis was able to inhibit the growth of several microorganisms, including S. aureus, Candida albicans, Pseudomonas aeruginosa, and Leishmania sp.

Ursolic acid, a pentacyclic triterpene from Sambucus australis, prevents abdominal adiposity in mice fed a high-fat diet.

Currently, there is renewed interest in plant-based medicines and functional foods for the prevention and cure of obesity and its associated risk of cardiovascular disease and metabolic syndrome. In the search for potential anti-obesity compounds from natural sources, the effects of ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, was evaluated for its effects on blood glucose, lipids, and abdominal fat deposition in mice fed a high-fat diet (HFD). Adult male Swiss mice treated or not with UA (0.05%, 50 mg/L, in drinking water) were fed HFD for 15 weeks. A sibutramine (SIB)-treated group (0.05% in drinking water) was included as the positive control. Weekly body weights and food and water consumption were measured, and at the end of the study period, the levels of blood glucose and lipids, the plasma hormones insulin, ghrelin, and leptin, and the abdominal fat accumulation were analyzed. Mice treated with UA and fed HFD showed significantly (P<.05) decreased body weights, visceral adiposity, and levels of blood glucose and plasma lipids relative to their respective controls not fed UA. Also, a significant increase was observed in plasma leptin with a decrease in ghrelin, as well as of amylase and lipase activities. The SIB-treated group also manifested effects similar to those of UA except for the blood glucose level, which was not different from the HFD control. These findings suggest that UA ameliorates abdominal adiposity and decreases the levels of blood glucose and plasma lipids in mice and thus manifests an anti-obesity potential through absorptive and metabolic targets.

Effects of Bixa orellana L. Seeds on Hyperlipidemia

Bixa orellana L., urucum, or urucu, a native tropical tree of Central and South American rain forests is used to treat various diseases in popular medicine. In Ceará, Northeast of Brazil, the seeds of urucum have been used for the treatment of high lipid blood levels. The present study investigated the effects of the aqueous extract from Bixa orellana seeds (AEBO) in mice with hyperlipidemia induced by tyloxapol, fructose and ethanol. In hyperlipidemia induced by Triton WR1339, 400 and 800 mg/kg AEBO reduced triglycerides (TG) serum levels at 24 h and 48 h. In the study of hypertriglyceridemia induced by fructose, AEBO in doses of 400 mg/kg and 800 mg/kg reduced TG levels by 48.2% and 48.7%, respectively. Finally, the ethanol experimental model with 400 mg/kg AEBO promoted a reduction of 33.6% of TG levels, while the 800 mg/kg concentration reduced hypertriglyceridemia in 62.2%. In conclusion, the aqueous extract of the seeds of Bixa orellana was capable of reversing the hypertriglyceridemia induced by Triton, fructose and ethanol, demonstrating a hypolipidemic effect. However, further studies are necessary to discover the precise mechanism of action. Copyright

Atividade farmacológica da monocrotalina isolada de plantas do gênero Crotalaria

Crotalia retusa is a plant found in Brazilian Northeast and belongs to the genus Crotalaria and the family Leguminosae, which comprises more than 600 species throughout the world and more than forty in Brazil. The most known toxic species are C. spectabilis, C. crispata, C. retusa, C. dura and C. globifera. Plants of the Crotalaria genus are of great interest because they are used by humans for folk medicine. These plants are rich in pyrrolizidine alkaloids (PA), which are the main toxins that cause effects such as pneumotoxic, nefrotoxic, cardiotoxic, fetotoxic, carcinogenic, inflammation, hemorrhage and fibrosis. Monocrotaline is the main pirrolizidinic alkaloid found in plants and is actively oxidated in vivo by the cytochrome P450 in the liver, yielding highly reactive pyrrolic type intermediates, which are responsible for DNA-DNA and DNA-protein cross-links reaction. The aim of this work is to make a bibliographic survey via internet, using databases, scientific research programs and related books, about pharmacological activity and mechanism of action of monocrotaline extracted from plants of Crotalaria genus, emphasizing plant botanical aspects, chemical structure of pirrolizidinic alkaloid, experimental examples of toxicity and probable action mechanism.

Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells

Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivo tumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.

Cardiovascular risk rate in hypertensive patients attended in primary health care units: the influence of pharmaceutical care

Cardiovascular complications are relevant due to their frequency and severity on the hypertension scenario. Studies refer Pharmaceutical Care (PC) as capable of decreasing cardiovascular risk rate (%CVR) on hypertensive patients. This study aimed to investigate, through a randomized clinical assay, the influence of PC service on the %CVR of hypertensive patients assisted in a health primary care unit from Fortaleza-Ceara. Two study groups were formed: i. Intervention Group (IG), which received orientation about taking medicines, actions aiming to prevent/solve medicine interactions and adverse effects and non-pharmacological interventions for 9 months and, ii. Control Group (CG), which received traditional assistance of the unit and was monitored during the same period. It was observed a statistically significant reduction on %CVR (10.76 to 7.86; p=0.04) and systolic blood pressure levels (SBP) (137.69 to 131.54; p<0.01) in the IG, while, in the CG, there was no significant alteration. 151 Drug Related Problem (DRP) were identified and it was realized 124 pharmaceutical interventions, with 89.2% of them resulting on solution/prevention of the problem. Our findings indicated that the inclusion of the PC service in the hypertensive health assistance was more effective at the %CVR and the SBP reduction in comparison to the traditional assistance offered.

Parâmetros séricos de bezerros submetidos a diferentes tipos dietas líquidas

This study was conducted to evaluate the influence of the liquid diet on the blood metabolites profile related to the protein and energy status of calves receiving different liquid diets. Twenty-four calves of Holstein x Gir breed were distributed in a completely randomized design with four treatments and six replications: Whole milk (Control); 50% whole milk + 50% of whey of cheese in natura; 50% whole milk + 50% of cheese whey in natura + one egg in natura; 50% whole milk + 50% of cheese whey in natura + one egg in natura + of biotin. The adaptation of the animals to the experimental diets occurred ten days before the beginning of the treatments. The animals received concentrate, Tifton-85 (Cynodon sp.) hay and water ad libitum from the birth to wean. Samples of blood were weekly collected in the morning, before the supply of the liquid diet and two hours after the ingestion. The concentrations of glucose, urea, creatinin, total proteins and albumin found in the serum of the calves, between liquid diets tested, were within normal limits when compared to reference levels in the literature. Only the values of urea differ significantly between treatments, but without harming the performance of the animals, soon it can be used the cheese whey in substitution to the whole milk, in the proportion of 50%, without egg or biotin addition, for a redution on the production cost.

α-lipoic Acid as Adjunctive Treatment for Schizophrenia: An Open-label Trial

Purpose/Background Accumulating evidence suggests an involvement of oxidative stress in the pathophysiology of schizophrenia. This offers a hypothesis-derived therapeutic approach to hinder oxidative damage and its clinical sequelae. &agr;-Lipoic acid (ALA) is a powerful natural antioxidant indicated to treat diabetic neuropathy. Methods/Procedures In this pilot investigation, we administered ALA (100 mg/d) for 4 months, as an adjunct to antipsychotic medication, to 10 patients with schizophrenia. Findings/Results We found robust improvement in measures of psychopathology (63.9% reduction in Brief Psychiatric Rating Scale scores), neurocognitive parameters, extrapyramidal symptoms, and decreased lipid peroxidation. Implications/Conclusions If larger, double-blind, placebo-controlled studies confirm these preliminary findings, ALA could prove useful as adjunctive therapy for schizophrenia.