Search

Monocrotaline (MCT) is a bioactive pyrrolizidine alkaloid (PAs) isolated from Crotalaria retusa seeds. The PAs when taken orally may be toxic to animals and humans. However, studies of pyrrolizidine alkaloids in topic formulations did not show toxic effects, otherwise demonstrated several pharmacological activities. The goal of the present work was to characterize MCT employing thermal analysis (DSC, TG/DTG and DTA) and non-thermal techniques (FTIR and capturing images of the decomposition process). The TG curves presented five mass loss events, at a heating rate of 10 °Cmin−1, being the third event, occurring between 204 °C and 292 °C, the one with the greater decomposition, with a mass loss of 62.2% and with an initial decomposition temperature of about 100 °C. Five events (three endothermic and two exothermic) were observed in the DSC curves at the same heating rate. The first event occurred at temperatures between 133 °C and 149 °C. A sample contraction was observed in the images captured at 150 °C, and it was attributed to a part of the decomposition process. Furthermore, the images of the decomposition process revealed that the sample melts at around 202 °C, which was the temperature of the second event of the DSC curve. The other three events were attributed to the sample decomposition. DTA curves were similar to the DSC curves. Fourier transform infrared spectrometry (FTIR) was employed to compare the spectra of the heated samples at several temperatures (50, 100, 150, 200 and 250 °C), with the spectrum of monocrotaline at room temperature. The spectra were compared by an ad hoc algorithm that performs Pearson correlation analysis. FTIR showed that monocrotaline had a significant change in its structure at 150 °C. The kinetic parameters for degradation process were calculated through the experimental data adjustment in the temperature range of 170–300 °C, using a general kinetic model, which was firstly proposed by Ng and improved by Cai-Liu. The results detected a contribution of kinetic models, mainly geometrical contraction models, with activation energy of 108.39 kJ mol−1 and frequency factor of 4.464 × 1011 min−1. This result corroborates the sample contraction, as seen by the images. With the results of mass loss obtained in the thermogravimetric analysis, the thermal degradation mechanism was proposed in association with the FTIR results.

INTRODUCTION Given the diversity of secondary metabolites produced by species of the genus Erythroxylum, in addition to the many methods that have already been described in the literature, modern screening and identification methodologies, such as dereplication, represent an efficient and quick strategy compared to the classic techniques linked to natural product research. OBJECTIVE The objective of the present study was to determine the phenolic profiles obtained from three species of Erythroxylum (Erythroxylum pauferrense Plowman, Erythroxylum pulchrum A.St.-Hil. and Erythroxylum simonis Plowman) by dereplication using liquid chromatography coupled with ESI-MSn and HRESIMS. MATERIAL AND METHODS Ethyl acetate and n-butanolic fractions from crude ethanolic extract of Erythroxylum species were analyzed by HPLC-ESI-MSn and HPLC-HRESIMS, in order to identify its corresponding compounds. Experiments were performed in negative ionization mode, and the metabolites were provisionally identified based on deprotonated molecules, molecular formulas, fragmentation patterns and literature data. The corresponding isolated compounds were characterized by 1 H and 13 C NMR spectroscopy. RESULTS According to the dereplication method, it was possible to establish and compare the phenolic profile of the corresponding species by the assignment of 55 compounds, most of which were first described in these species and among which some were also new to the Erytroxylum genus. Additionally, nine compounds were isolated, including biphenyl-3,3',4,4'-tetraol, where the mass spectral data were not sufficient for their identification, and reported for the first time in the Erythroxylaceae family. CONCLUSION This research contributes to the phytochemical knowledge of the Erythroxylum genus and demonstrates the importance of the dereplication method regarding the investigation of natural products, enabling accurate identification of the metabolites while avoiding the efforts and material expenses involved in the isolation of known compounds.

The chemical investigation of Macroptilium martii (Fabaceae) has provided the identification of twelve compounds obtained by liquid chromatography coupled to mass spectrometry (LC–MS/MS), among which, a new flavonoid: isorhamnetin-3-O-galactose-6′'-O-rhamnose-4′”-O-galactose-2-methylbutyric acid (10) and two other flavonoids already reported. The structural elucidation of the new compound was carried out by HR-ESI-MS spectrometric analysis, 1H, 13C and two-dimensional NMR. Cytotoxic activity of 10 was evaluated towards HCT-116 (colorectal carcinoma), HeLa (cervical carcinoma), SK-MEL-28 (melanoma), PC-3 (prostate cancer) and MDA-MB-231 (breast cancer) cells.

Stigmurin is a peptide with amidated C-terminus (FFSLIPSLVGGLISAFK-NH2) identified in the transcriptome of the scorpion Tityus stigmurus that has shown antimicrobial action against methicillin-resistant pathogens and low antihemolytic activity, and recently proved to be efficient in controlling sepsis. Despite its pharmacological potential, there is no report about thermal studies for the characterization of the amorphous solid. The objective of this work is to characterize stigmurin using thermoanalytical techniques in the solid state in an inert and oxidative atmosphere. Stigmurin presents glass transition temperature at 149 °C. The results of TG–FTIR and pyrolysis suggest that the pathways for decomposition include homolytic breakdown of the side chains of amino acid residues. Decomposition possibly begins at the N-terminus, with formation of the aromatic compounds, amines, nitriles, alcohols, and ethers among others followed by defragmentation reactions (mainly decarboxylation and deamination) and intramolecular condensation reactions. It generates compounds similar to 2,5-diketopiperazine or DKP, and releases water and low molecular mass products (CO2, NH3, CO, HCNO). The decomposition of stigmurin is an endothermic process where the product of decomposition is originated in the liquid state according to DSC-photovisual images. Stigmurin is more stable in nitrogen atmosphere than synthetic air. This approach provides important information about the thermal decomposition of stigmurin, a molecule endowed with potent antimicrobial activity, supplying relevant parameters (temperature, degradation products, etc.) for technological strategies focusing on quality control and development studies of preformulation involving stigmurin and synthetic peptides in general.

Metabolomics has been increasingly used to evaluate metabolic changes associated with morbidities. The objective of this study is to assess the metabolic profile before and after intervention with mixed dietary fiber in overweight and obese hypertensive women. This is an intervention study, and the sample consists of 14 women aged 28 to 58 years. An intervention with 12 g of mixed soluble and insoluble fiber is performed for a period of eight weeks. Serum metabolites are identified using a Bruker 1H NMR spectrometer at 400 MHz. Multivariate data analysis, including principal component analysis (PCA), is used to differentiate the two groups. After supplementation with dietary fiber, there is a significant increase in the peak intensity values of the metabolites HDL-C (0.0010*), choline (0.0012*) and hydroxybutyrate (0.0010*) as well as a decrease in systolic (0.0013*) and diastolic (0.0026*) blood pressure. The analysis of the metabolomic profile allows the identification of metabolites that have been associated in the literature with hypertension and excess weight (choline, hydroxybutyrate and amino acids) and with fiber intake (choline, hydroxybutyrate and amino acids) in addition to an increase in HDL-C. The increase in the detection of the described metabolites possibly occurs due to the presence of pathologies and the use of fiber in the intervention, which also contributes to elevated HDL-c and reduced blood pressure.

This current study presents the phytochemical analysis of Croton velutinus, describing phenylpropanoids obtained from this species. The fractionation of the roots hexane extract led to the isolation of four new phenylpropanoids derivatives, velutines A–D (1–4) and three known (5–7). Their structures were established based on spectroscopic (1D-2D NMR; HRMS and IR) analysis. Cytotoxic, trypanocidal and anti-inflammatory activities of compounds 1–7 were evaluated. Only compounds 2 and 5 showed cytotoxic activity against cancer cell lines (B16F10, HL-60, HCT116, MCF-7 and HepG2), with IC50 values ranging from 6.8 to 18.3 μM and 11.1 to 18.3 μM, respectively. Compounds 2 and 5 also showed trypanocidal activity against bloodstream trypomastigotes with EC50 values of 9.0 and 9.58 μM, respectively. Finally, the anti-inflammatory potential of these compounds was evaluated on cultures of activated macrophages. All compounds exhibited concentration-dependent suppressive activity on the production of nitrite and IL-1β by macrophages stimulated with LPS and IFN-γ. These results indicate phenylpropanoids esters (2 and 5) from C. velutinus as promising cytotoxic, trypanocidal and anti-inflammatory candidates that warrants further studies.

The first occurrences and dissemination of resistant microorganisms led to the inefficacy of many antibiotics, available in the market nowadays, therefore, the search for new substances with antimicrobial activity from natural sources has gained a great importance. The purpose of this work is to evaluate the antibacterial activity and modulation of drug resistance in Staphylococcus aureus by coumarins such as bergapten, xantotoxin, isopimpinellin and imperatorin obtained from two Rutaceae species (Metrodorea mollis and Pilocarpus spicatus). The antimicrobial activity was assessed based on the minimum inhibitory concentration (MIC), using the microdilution method. The MIC was >256 g/mL for all coumarins tested. Regarding the modulation of drug resistance assay, the isopimpinellin reducted the MIC of erytromicin by 4 times, whereas imperatorin exhibited the best result, reducing the MIC of tetracycline (2 times), erytomicin (4 times) and norfloxacin (4 times). By reducing the MIC of ethidium bromide, the imperatorin is consider in fact, as a putative efflux pump inhibitor of bacteria.

Made available in DSpace on 2020-12-11T09:37:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Universidade Federal do Rio Grande do Norte (UFRN) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Prosopis juliflora is an invasive plant distributed throughout the world and presents metabolites of interest for cosmetology. The aim of this work was to develop a new polysaccharide-based ingredient from P. juliflora and analyze its application in a solid core formulation that upon contact with water instantly forms a gel to improve moisturizing and anti-aging skin properties. Purified extracts by gel chromatography were characterized by NMR and LC-DAD-MS-MS. The in vitro and in vivo safety, antioxidant activity, formulation development and clinical evaluation were performed. The extract was characterized as containing an a-glucan and phenolics. It was non-cytotoxic, non-phototoxic and no skin reactions were observed in vivo. Antioxidant activity were present through different mechanisms. Clinical evaluation reinforced the potential of P. juliflora in skin hydration and microrelief improvement. This innovative form proved to be a prototype of a new product and the first study of an a-glucan as a cosmetic ingredient. Fed Univ Rio Grande Norte UFRN, R Gen Gustavo Cordeiro de Faria S-N Petropolis, BR-59012570 Natal, RN, Brazil Fed Univ Rio Grande Norte UFRN, Nucleo Pesquisa Alimentos & Med NUPLAM, Av Sen Salgado Filho 3000 Candelaria, BR-5906474 Natal, RN, Brazil Fed Univ Parana UFPR, Av Cel Francisco H Dos Santos 100 Jardim Das Amer, BR-81530000 Curitiba, PR, Brazil Fed Univ Sao Paulo UNIFESP, Sao Nicolau 210 Ctr, BR-09913030 Diadema, SP, Brazil Sao Paulo State Univ Julio de Mesquita Filho, Rua Prof Francisco Degni 55 Quitandinha, BR-14800060 Araraquara, SP, Brazil Sao Paulo State Univ Julio de Mesquita Filho, Rua Prof Francisco Degni 55 Quitandinha, BR-14800060 Araraquara, SP, Brazil CAPES: 001 CNPq: 445149/2014-0

The use of the voltammetry of immobilized particles (VIMP) approach, by means of the voltammetric response of microparticulate films from ethanolic leaf extracts in contact with aqueous electrolytes and direct contact probe leaf voltammetry, to monitor the defense of plants against external stressors is described. This approach is applied to study the chemical communication between plants of Peperomia obtusifolia A. Dietr. submitted to herbivory by the beetle Monoplatus sp.

The essential oil from leaves of Croton grewioides Baill was obtained by hydrodistillation using Clevenger apparatus, and its chemical composition was analyzed by GC-MS, where 18 compounds were identified, mostly as monoterpenes (55.56%) and sesquiterpenes (44.44%), in which the major constituent was the α-pinene (47.43%). The essential oil of Croton grewioides (EOCg) and its major compound (α-pinene) were evaluated as modulators of antibiotic resistance in strain SA-1199B and IS-58 of Staphylococcus aureus that overexpresses efflux protein. The minimum inhibitory concentrations (MICs) of the antibiotics were determined by the microdilution assay in the absence and in the presence of sub-inhibitory concentration of EOCg and α-pinene. Although the EOCg and α-pinene did not indicate relevant antibacterial activity in vitro, they acted as antibiotic resistance modulators, i.e., EOCg in combination with norfloxacin, reducted its MIC, by 64× whereas in combination with tetracycline it was observed a reduction of 4×. Additionally, it was observed a MIC reduction of tetracycline by 32×, when combined with α-pinene. The results suggest that EOCg and α-pinene modulate or even reverse bacterial resistance as a putative efflux pump inhibitor.

This study investigates the gastroprotective effects of hecogenin, a steroid saponin isolated from Agave sisalana, on experimental models of gastric ulcer. Male Swiss mice were used in the models of ethanol- and indometacin-induced gastric ulcer. To clarify the hecogenin mechanism of action, the roles of nitric oxide (NO), sulfhydryls (GSH), K+ATP channels and prostaglandins were also investigated, and measurements of lipid peroxidation (TBARS assay) and nitrite levels in the stomach of hecogenin-treated and untreated animals were performed. Furthermore, the effects of hecogenin on myeloperoxidase (MPO) release from human neutrophils were assessed in vitro. Our results showed that hecogenin (3.1, 7.5, 15, 30, 60 and 90mg/kg, p.o.) acutely administered, before ethanol or indomethacin, exhibited a potent gastroprotective effect. Although the pretreatments with L-NAME, an iNOS inhibitor, and capsazepine, a TRPV1 receptor agonist, were not able to reverse the hecogenin effect, this was reversed by glibenclamide, a K+ATP blocker, and indomethacin in the model of ethanol-induced gastric lesions. The hecogenin pretreatment normalized GSH levels and significantly reduced lipid peroxidation and nitrite levels in the stomach, as evaluated by the ethanol-induced gastric lesion model. The drug alone increased COX-2 expression and this effect was further enhanced in the presence of ethanol. It also decreased MPO release and significantly protected the gastric mucosa. In conclusion, we showed that hecogenin presents a significant gastroprotective effect that seems to be mediated by K+ATP channels opening and the COX-2/PG pathway. In addition, its antioxidant and anti-inflammatory properties may play a role in the gastroprotective drug effect.

Many natural substances with proven anti-inflammatory activity have been isolated throughout the years. The aim of this review is to review naturally sourced alkaloids with anti-inflammatory effects reported from 2000 to 2010. The assays were conducted mostly in vivo, and carrageenan-induced pedal edema was the most used experimental model. Of the 49 alkaloids evaluated, 40 demonstrated anti-inflammatory activity. Of these the most studied type were the isoquinolines. This review was based on NAPRALERT data bank, Web of Science and Chemical Abstracts. In this review, 95 references are cited.