Aldose reductase, E.C.1.1.1.21, catalyzes the reduction of different types of aldehydes to their corresponding alcohols, and especially reduces various aldo-sugars using NADPH as the coenzyme. Under hyperglycemic conditions aldose reductase is involved in the development of diabetic complications. As a result, interest has been placed over the years on the development of potent aldose reductase inhibitors for possible use in the therapy of these severe diabetic complications. In this study, aldose reductase was isolated from bovine lens by differential centrifugation and ammonium sulfate precipitation. The conditions for the enzyme assay / such as substrate (DL-Glyceraldehyde) and coenzyme (NADPH) concentration, protein amount, effect of sulfate ions, temperature and pH on the enzyme activity were optimized. The inhibitory effects of Punica granatum, Spinacia olaeracea, Allium cepa Allium porrum, Malus flouribunda, Malus domestica extracts were tested on crude bovine lens aldose reductase. Four different types of organic fractions from each crude plant extract were obtained by solvent fractionation. The inhibitory activity of these organic fractions was calculated considering the aldose reductase activity without extracts as 100 %. All six plants were found to inhibit aldose reductase activity to different extent. Among these fractions obtained as / petroleum ether, diethyl ether, ethyl acetate, and n-butanol. Highest inhibitory activity was found for the ethyl acetate fraction. The IC50 values of ethyl acetate fractions of all these plants was calculated as, 25.46 &micro / g/ml, 20.5 &micro / g/ml, 18.5 &micro / g/ml, 12.32 &micro / g/ml, 6.45 &micro / g/ml, 5.4 &micro / g/ml, for Allium porrum, Malus domestica, Spinacia olaeracea, Malus floribunda Allium cepa, Punica granatum respectively.

Diss. (sammanfattning) Alnarp : Sveriges lantbruksuniv. / Härtill 4 uppsatser.

Thesis (Ph. D. (Pharmacy))--Rhodes University, 2006.

Thesis (M.S.)--Universidad de Puerto Rico, Recinto Universitario de Mayagüez, 2005. / Tables. Printout. Includes bibliographical references (leaves 68-73)

Thesis (MScFoodSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: The flavanone aglycones, hesperetin and eriodictyol, have been identified as potential taste modulators with reported sweetness-enhancing and bitterness-masking properties, respectively. Reduction of the sugar content of food products has become important in view of the global obesity epidemic. Taste modulators have shown potential to enhance the sweet taste of reduced-sugar foods without unfavourably affecting their flavour profile. On the other hand, bitterness-masking taste modulators are useful to mask the bitter taste of functional phytochemical ingredients. In the current study, Cyclopia maculata (honeybush) was investigated as potential source of hesperetin- and eriodictyol-enriched extracts. Hesperetin and eriodictyol were present mainly below the quantification limit in C. maculata plant material, including unfermented leaf and stem material, unfermented and fermented tea, as well as the fermented by-product (< 40 mesh and > 12 mesh). Conversely, their rutinoside and modulatinginactive derivatives, hesperidin and eriocitrin were present at substantially higher concentrations in the plant material. The stems and by-product were shown to be good sources of hesperidin, but not eriocitrin. The qualitative and quantitative phenolic profile of the by-product was similar to that of the stems. The tea processing by-product was therefore selected to optimise extraction of flavanone glycosides for subsequent de-glycosylation of the flavanone glycosides to aglycones. The by-product was subjected to ultrasound-assisted extraction to investigate its potential as renewable source of the flavanone glycosides. Response surface methodology (RSM) was employed to optimise and study the individual and interactive effects of the process variables, namely ethanol concentration (% v/v), time (min), temperature (°C), and solvent:solid ratio (mL/g), on flavanone glycoside extraction. The hesperidin yield and content (of extract), as well as extract yield, increased with an increase in extraction time, temperature and solvent:solid ratio. Practical process restrictions limited global optimisation and only an optimum of 52.8% (v/v) ethanol for extract and hesperidin yield could be reached. Temperature was the parameter with the most significant effect (p < 0.05) on extraction efficiency among those studied. Practical process parameter values that were feasible for industrial application (52.8% (v/v) ethanol, 20 mL/g solvent:solid ratio, 60°C and 30 min) were selected for the preparation of a flavanone glycoside-enriched extract from the tea processing by-product. The flavanone glycoside-enriched extract was subjected to acid-catalysed hydrolysis to deglycosylate hesperidin and eriocitrin to hesperetin and eriodictyol, respectively. RSM was employed to optimise the acid hydrolysis process and to study the effect of the hydrolysis parameters (temperature (°C) and time (min)) on hydrolysis efficiency. At the maximum temperature (92.1°C) and corresponding optimum time (98.4 min) ca 80% conversion of hesperidin to hesperetin was achieved. Substantially more eriodictyol formed during acid hydrolysis than eriocitrin present in the initial extract owing to the deglycosylation of unidentified glycosides with the same aglycone. Unidentified breakdown products imparting a red colour to the acid-hydrolysed extract were also observed. The total phenolic content of the acid-hydrolysed extract was significantly higher (p < 0.05) than that of the unhydrolysed extract, indicating the formation of unidentified compounds with the ability to reduce the Folin-Ciocalteau reagent, although no significant difference (p ≥ 0.05) between the antioxidant activities of these extracts, as assessed with the DPPH radical scavenging and ORAC assays, was observed. The potential of enzymatic bioconversion as an alternative to acid-catalysed hydrolysis was investigated using commercial hesperidinase. Bioconversion resulted only in de-rhamnosylation with ca 100% conversion of hesperidin to hesperetin-7-O-glucoside in an aqueous C. maculata extract at pH 4.0 and 40°C. / AFRIKAANSE OPSOMMING: Die flavanoon aglikone, hesperetien and eriodiktiol, is geïdentifiseer as potensiële smaakmoduleerders met berigte soetheid-versterkende en bitter-maskerende eienskappe, onderskeidelik. Vermindering van die suikerinhoud van voedselprodukte het belangrik geword in die lig van die wêreldwye vetsugepidemie. Smaakmoduleerders het die potensiaal getoon om die soet smaak van voedsel met verlaagde suikerinhoud te versterk sonder om hul geurprofiel ongunstig te beïnvloed. Andersyds is bittermaskerende smaakmoduleerders nuttig om die bitter smaak van funksionele fitochemiese bestanddele te maskeer. In die huidige studie is Cyclopia maculata (heuningbos) ondersoek as ‘n potensiële bron van hesperetien- and eriodiktiol-verrykte ekstrakte. Hesperetien and eriodiktiol was hoofsaaklik teenwoordig onder die kwantifiseringsperk in C. maculata plantmateriaal, insluitend ongefermenteerde blaar- en stokmateriaal, ongefermenteerde en gefermenteerde tee, asook die gefermenteerde byproduk (< 40 maas en > 12 maas). Hierteenoor was hul rutinosiedes en modulerend-onaktiewe derivate, hesperidien and eriositrien, teenwoordig in aansienlik hoër konsentrasies in die plantmateriaal. Die stokmateriaal en byproduk is getoon om goeie bronne van hesperidien, maar nie eriositrien nie, te wees. Die kwalitatiewe en kwantitatiewe fenoliese profiel van die byproduk was soortgelyk aan dié van die stokke. Die teeprosesseringsbyproduk is dus geselekteer om die ekstraksie van flavanoonglikosiede, voorafgaande hul de-glikosilering na aglikone, te optimeer. Die byproduk is aan ekstraksie met behulp van ultrasoniese klank onderwerp om die potensiaal daarvan as hernubare bron van flavanoonglikosiede te ondersoek. Respons-oppervlak Metodologie (ROM) is gebruik om die individuele en wisselwerking effekte van die proses veranderlikes, naamlik etanolkonsentrasie (% v/v), tyd (min), temperatuur (°C), en oplosmiddel:vastestof verhouding (mL/g), op flavanoonglikosied ekstraksie te optimiseer en te bestudeer. Die hesperidienopbrengs en -inhoud (van ekstrak), sowel as die ekstrakopbrengs, het toegeneem met ‘n toename in die ekstraksietyd, - temperatuur en oplosmiddel:vastestof verhouding. Praktiese prosesbeperkings het die globale optimisering beperk en slegs ‘n optimum van 52.8% (v/v) etanol vir ekstrak- en hesperidienopbrengs kon bereik word. Temperatuur was die parameter met die mees beduidende effek (p < 0.05) op ekstraksie doeltreffendheid van dié wat bestudeer is. Praktiese prosesparameterwaardes wat haalbaar is vir industriële toepassing (52.8% (v/v) etanol, 20 mL/g oplosmiddel:vastestof verhouding, 60°C en 30 min) is geselekteer vir die voorbereiding van 'n flavanoonglikosied-verrykte ekstrak uit die teeprosesseringsbyproduk. Die flavanoonglikosied-verrykte ekstrak is aan suur-gekataliseerde hidrolise onderwerp om hesperidien en eriositrien na hesperetien en eriodiktiol, onderskeidelik, te de-glikosileer. ROM is gebruik om die suurhidrolise proses te optimeer en die effek van die hidrolise parameters (temperatuur (°C) en tyd (min)) op hidrolise doeltreffendheid te bestudeer. Ongeveer 80% omskakeling van hesperidien na hesperetien is behaal teen die maksimum temperatuur (92.1 °C) en ooreenstemmende optimum tyd (98.4 min). Aansienlik meer eriodiktiol is tydens suurhidrolise gevorm as eriositrien wat in die oorspronklike ekstrak teenwoordig was, as gevolg van de-glikosilering van ongeïdentifiseerde glikosiede met dieselfde aglikoon. Ongeïdentifiseerde afbreekprodukte, wat 'n rooi kleur aan die suurgehidroliseerde ekstrak gegee het, is ook waargeneem. Die totale fenoliese inhoud van die suurgehidroliseerde ekstrak was beduidend hoër (p < 0.05) as dié van die ongehidroliseerde ekstrak, wat die vorming van onbekende verbindings met die vermoeë om die Folin-Ciocalteau reagens te reduseer aandui, hoewel daar geen beduidende verskil (p ≥ 0.05) tussen die antioksidant-aktiwiteite van hierdie ekstrakte, soos bepaal met die DPPH radikaal blussings- en ORAC toetse, waargeneem is nie. Die potensiaal van ensiematiese bio-omskakeling as 'n alternatief vir suur-gekataliseerde hidrolise is ondersoek met behulp van kommersiële hesperidinase. Bio-omskakeling het slegs tot de-ramnosilering gelei met ca 100% omskakeling van hesperidien na hesperetien-7-O-glukosied in 'n C. maculata waterekstrak by pH 4.0 en 40°C.

Made available in DSpace on 2014-06-11T19:23:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-01Bitstream added on 2014-06-13T18:09:49Z : No. of bitstreams: 1 silveira_jq_me_arafcf.pdf: 547711 bytes, checksum: b59a161a868796ba9279f965c790ccc1 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Universidade Estadual Paulista (UNESP) / Tem sido evidenciado que o consumo do suco de laranja amarela melhora a sensibilidade insulínica, o perfil lipídico, a pressão arterial, o estresse oxidativo e a inflamação, condições fisiopatológicas relacionadas às doenças crônicas como cardiovasculares, síndrome metabólica, diabetes tipo II, obesidade e câncer. Tais efeitos se devem à presença de nutrientes (vitamina C e potássio) e compostos bioativos (flavonóides cítricos e carotenóides), que atuam de forma sinérgica protegendo o organismo. O suco de laranja de polpa vermelha apresenta além destes componentes, o licopeno que atua como um potente antioxidante celular. O objetivo desta pesquisa foi avaliar o efeito do consumo regular do suco de laranja vermelha sobre os fatores de risco da síndrome metabólica, incluindo circunferência da cintura aumentada, hipertrigliceridemia, baixo HDL-C, hipertensão arterial e intolerância à glicose. Os resultados obtidos foram analisados em dois diferentes estudos os quais foram escritos na forma de artigo científico, sendo que no primeiro foi dado ênfase nos parâmetros antropométricos e no segundo os parâmetros bioquímicos e hemodinâmicos. Homens e mulheres saudáveis consumiram diariamente 750mL de suco de laranja vermelha durante oito semanas consecutivas. No início e no final do tratamento foram realizadas avaliações antropométrica (peso corporal, estatura, dobras cutâneas e circunferências) bioquímica (glicose, insulina, hemoglobina glicada, colesterol total, LDL-C, HDL-C, Apo A e B, proteína C reativa, atividade antioxidante por DPPH, resistência insulínica pelo índice HOMA), hemodinâmica (pressão arterial sistólica e diastólica). O tratamento com o suco de laranja vermelha não alterou a circunferência da cintura, diminuiu o colesterol total, LDL-C, proteína C reativa e pressão arterial, além de aumentar a atividade antioxidante no soro... / It has been shown that the consumption of blond orange juice improves insulin sensitivity, lipid profile, blood pressure, oxidative stress and inflammation, pathophysiological conditions related to chronic diseases such as cardiovascular, metabolic syndrome, diabetes type II, obesity and cancer. These effects are due to the presence of nutrients (vitamin C and potassium) and bioactive compounds (citrus flavonoids and carotenoids), which act synergistically protects the body. Besides these components the red orange juice has lycopene that acts as a potent antioxidant. The aim of this study was to evaluate the effect of regular consumption of red orange juice on the risk factors of metabolic syndrome, including increased waist circumference, hypertriglyceridemia, low HDL-C, hypertension and glucose intolerance. The results were analyzed in two different studies which were written in the form of a scientific paper, the first one emphasizes the anthropometric parameters and in the second one biochemical and hemodynamics parameters. Healthy men and women consumed daily 750mL of red orange juice for eight consecutive weeks. At the beginning and end of treatment were evaluated anthropometric (body weight, height, skinfolds and circumferences) biochemical (glucose, insulin, glycated hemoglobin, total cholesterol, LDL-C, HDL-C, Apo A and B, C-reactive protein antioxidant activity by DPPH, insulin resistance by HOMA index), hemodynamic (systolic and diastolic). Treatment with red orange juice did not alter the waist circumference, decreased total cholesterol, LDL-C, C-reactive protein and blood pressure, besides increasing the antioxidant activity in serum of volunteers. We suggest that the orange juice does not influence the increase in body weight and other measures and has properties like hypolipidemic, anti-inflammatory and antioxidant... (Complete abstract click electronic access below)

Made available in DSpace on 2016-05-17T16:51:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-12-10. Added 1 bitstream(s) on 2016-05-17T16:55:55Z : No. of bitstreams: 1 000863704_20171210.pdf: 721153 bytes, checksum: 6ad0e2fa3c9bfbd7932a440bf72647d9 (MD5) Bitstreams deleted on 2017-12-15T12:43:39Z: 000863704_20171210.pdf,. Added 1 bitstream(s) on 2017-12-15T12:44:29Z : No. of bitstreams: 1 000863704.pdf: 4627489 bytes, checksum: 7ba9e741dcf10a9168b78e6f59344425 (MD5) / O estudo de produtos naturais como fonte de novos agentes anticâncer torna-se de grande importância, pois mesmo devido à grande quantidade de drogas já existente para o tratamento de neoplasias, ainda não se chegou a um composto ideal que tenha maior seletividade, menos efeitos colaterais, maior potência terapêutica e menor índice de resistência. Das famílias vegetais com reconhecido potencial terapêutico destaca-se a família Fabaceae, cuja quimiossistemática atesta para uma riqueza de compostos flavonoídicos com amplo espectro de atividade biológica, inclusive antitumoral. Desta forma, o objetivo principal deste estudo foi isolar e caracterizar substâncias fenólicas a partir de frações oriundas de espécies do gênero Inga (I. laurina, I. edulis e I. marginata) selecionadas através do bioensaio com linhagens de celulas antitumorais e identificar metabólitos em mistura através de CLAE-DAD, HPLC-MS, LC-SPE-TT e Espectroscopia de RMN. A composição química destas espécies indicou uma grande variedade de ácidos aromáticos, flavonóides, taninos e triterpenos. Este trabalho permitiu a caracterização das substâncias: lupeol, éster graxo da -amirina, éster do olean-18-eno, fridelina, ácido vanílico, ácido 3,4,5-trimetoxi-benzóico, ácido gálico, galato de metila, ácido pcumárico, ácido benzóico, p-hidroxi-benzóico, ácido protocateuico, ácido tânico, ácido cafeico, ácido p-metoxicinâmico, ácido p-hidroxibenzóico, derivado metilado do ácido 4-hidroxibenzóico, ácido ferúlico, miricetina,miricetina-3-O-ramnosídeo, miricetina-3-O-(2-Ogaloil)- -ramnopiranosídeo, apigenina, quercetrina, proantocianidina A-2, procianidina B, galato de 2-ramnopiranosil-4,6-diidroxifenila, galato de 2-ramnopiranosil-3,5-diidroxifenila e do glicosídeo do 4-vinil-fenol. Através das analises por CLAE-DAD detectamos a presença de uma antocianina altamente polar na fração aquosa... / The study of natural products as a source of new anticancer agents is very important, because even due to the large amount of existing drugs for the treatment of cancer, has not yet reached an optimal compound that has greater selectivity, fewer side effects, higher potency therapeutic and index of least resistance.One of thefamilies with recognized therapeutic potential is the Fabaceae family, whose chemosystematics show an abundance of flavonoid with broad spectrum of biological activities, including antitumor. Thus, the aim of this study was to isolate and characterize phenolic compounds from fractions obtained of the genus Inga (I. laurina, I. edulis and I. marginata) selected by bioassay cytotoxic and identify metabolites in mixture by HPLC-PDA, HPLC-MS, LC-SPE-TT and NMR Spectroscopy. The chemical composition of these species indicated a wide variety of aromatic acids, flavonoids, tannins and triterpenes. This work describe the characterization of the compounds: lupeol, fatty ester of -amyrin, the olean-18-ene ester and friedelin, vanillic acid, 3,4,5-trimethoxy benzoic acid, gallic acid, gallate methyl, p-coumaric acid, benzoic acid, p-hydroxybenzoic, protocateuico acid, tannic acid, caffeic acid, p-methoxycinnamic acid, p-hydroxybenzoic acid derivative methylated of 4-hydroxybenzoic acid, ferulic acid, myricetin, myricetin-3-Orhamnoside, myricetin-3-O- (2 -O-galoil) - -rhamnopyranoside, apigenin, quercetrin, proanthocyanidin A-2 and procyanidin B, 2-rhamnopyranosyl-3,5-dihydroxyphenyl gallate, 2-rhamnopyranosyl-4,6-dihydroxyphenyl gallateand 4-vinyl-phenol. Through the analysis by HPLC-PDA detected the presence of one anthocyanin from aqueous fraction in five other anthocyanins in the methanolic fraction from seeds of I. edulis. Through the bioassay-guided fractionation was possible to obtain a fraction with high antitumor potential (ED50 = 4.0 mg/mL) that was characterized such a mixture...

Made available in DSpace on 2015-05-14T12:59:34Z (GMT). No. of bitstreams: 1 arquivototal.PDF: 7069577 bytes, checksum: 994737d813443da6d7f127b17873faf9 (MD5) Previous issue date: 2012-03-01 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The flavonoid galetin 3,6 dimethyl ether (FGAL) was isolated from the aerial parts of Piptadenia stipulacea (Benth.) Ducke and was investigated its possible hemolytic activity in rat erythrocytes and spasmolytic activity in several isolated smooth muscles as rat uterus, guinea pig ileum and trachea, and rat aorta. FGAL showed no hemolytic effect on rat erythrocytes, which is suggestive of a low toxicity. In preliminary pharmacological screening performed in smooth muscle models, FGAL showed non-selective spasmolytic effect in the four organs tested, with a higher potency to relax the guinea pig trachea pre-contracted with carbachol and rat aorta pre-contracted with phenylephrine (FEN) in a functional epithelium and endothelium independent manner, respectively. The aim of this study was to investigate the action mechanism of FGAL relaxing effect in guinea pig trachea and rat aorta. The observation that FGAL was more potent in relaxing both pre-contracted organs with moderate increases in extracellular concentration of KCl than when contracted with larger increases of KCl is suggestive that FGAL modulates the channels positivety. This hypothesis was confirmed by decreasing of relaxant potency of FGAL in both organs in the presence of tetraethylammonium (TEA+) 10 mM, non-selective blocker of K+ channels. To determine the subtypes of K+ channel involved, were used selectives blockers: in trachea the effect of FGAL was not altered in the presence of TEA+ 1 mM, blocker of large conductance calcium-activated K+ channels (BKCa); glibenclamide, blocker of sensitive-ATP K+ channels (KATP); BaCl2, blocker of inward rectifier K+ channels (Kir) or 4-AP, blocker of voltage activated K+ channels (KV), but was reduced in the presence of apamin, blocker of small conductance calcium-activated K+ channels (SKCa). In aorta, the relaxant effect of FGAL was not altered in the presence of TEA+ 1 mM, but was reduced in the presence of apamin, glibenclamide, BaCl2 and 4-AP, suggesting the involvement of SKCa, KATP, Kir and KV in vasorelaxant action of flavonoid. The fact of FGAL rightward shifted, with Emax reduced the CaCl2-induced contractions in depolarizing medium, and CaCl2 in the presence of verapamil, a voltage activated calcium channel (CaV) blocker, and FEN, suggests the involvement of CaV and ROCs (receptor-operated calcium channel), respectively. Also in the aorta, FGAL inhibited FEN induced contractions in Ca2+-free medium, suggesting inhibition of Ca2+ release from the sarcoplasmic reticulum SR. We also evaluated the participation of the cyclic nucleotides pathway, and observed that the trachea and aorta relaxation induced by aminophylline, non selective inhibitor of phosphodiesterases (PDEs), was more potent in the presence of FGAL, suggesting the involvement of cAMP and/or cGMP. On the aorta was assessed FGAL effect on relaxation induced by selective inhibitors of PDE-3 (milrinone, cAMP selective) and PDE-5 (sildenafil, cGMP selective), and FGAL only potentiated the relaxation induced by sildenafil, suggesting the participation of cGMP. Since K+ channels are modulated negatively by PKC, we investigated a possible inhibition of PKC by FGAL and the flavonoid relaxed the aorta pre-contracted with a PKC activator (PMA), suggesting inhibition of this enzyme. In conclusion, the spasmolytic mechanism of FGAL in trachea involves positive modulation of SKCa and cyclic nucleotides, and in the aorta involves the positive modulation of KATP, SKCa, Kir, Kv and inhibition of CaV, ROCs, Ca2+ release of SR, PDE-5 and PKC. / O flavonoide 3,6-dimetil éter galetina (FGAL) foi isolado das partes aéreas de Piptadenia stipulacea (Benth.) Ducke e foi investigada sua possível atividade hemolítica em eritrócitos de rato e espasmolítica em vários músculos lisos isolados como útero de rata, íleo e traqueia de cobaia, e aorta de rato. FGAL não causou efeito hemolítico em eritrócitos de ratos, o que é sugestivo de baixa toxicidade. Na triagem farmacológica preliminar realizada em músculos lisos, FGAL apresentou efeito espasmolítico não seletivo nos 4 órgãos testados, apresentando uma maior potência em relaxar a traqueia de cobaia pré-contraída com carbacol e a aorta de rato pré-contraída com fenilefrina (FEN), de maneira independente de epitélio e endotélio funcional, respectivamente. Assim, o objetivo deste trabalho foi investigar o mecanismo de ação relaxante de FGAL em traqueia de cobaia e aorta de rato. A observação de que FGAL foi mais potente em relaxar ambos os órgãos pré-contraídos com aumentos moderados na concentração extracelular de KCl do que quando contraídos com aumentos maiores de KCl é sugestivo de que FGAL está agindo por modular positivamente os canais de K+, hipótese esta confirmada pela diminuição da potência relaxante de FGAL em ambos os órgãos na presença de tetraetilamônio (TEA+) 10 mM, bloqueador não seletivo dos canais de K+. Para verificar os subtipos de canais de K+, usou-se bloqueadores seletivos: em traqueia o efeito de FGAL não foi alterado na presença de TEA+ 1 mM, bloqueador dos canais K+ de grande condutância ativados pelo Ca2+ (BKCa), glibenclamida, bloqueador dos canais de K+ sensíveis ao ATP (KATP), BaCl2, bloqueador dos canais de K+ retificadores de entrada (Kir) ou de 4-AP, bloqueador dos canais de K+ sensíveis à voltagem (KV), porém foi reduzido na presença de apamina, bloqueador dos canais de K+ de pequena condutância ativados pelo Ca2+ (SKCa). Em aorta, o efeito relaxante de FGAL não foi alterado na presença de TEA+ 1 mM, por outro lado foi reduzido na presença de apamina, glibenclamida, BaCl2 e 4-AP, sugerindo a participação dos SKCa, KATP, Kir e KV na ação vosorrelaxante do flavonoide. O fato de FGAL deslocar para direita com redução do Emax as contrações induzidas por CaCl2 em meio despolarizante, e por CaCl2 na presença de FEN e verapamil, bloqueador de CaV, sugere o envolvimento dos CaV e dos ROCs, respectivamente. Ainda em aorta, FGAL inibiu as contrações induzidas por FEN em meio livre de Ca2+, sugerindo inibição da liberação de Ca2+ do retículo sarcoplasmático (RS). Avaliou-se ainda a participação dos nucleotídios cíclicos, e observou-se que o relaxamento induzido pela aminofilina, inibidor não seletivo de fosfodiesterases (PDEs) em traqueia e aorta foi potencializado com FGAL, sugerindo a participação de AMPc e/ou GMPc. Em aorta foi avaliado o efeito de FGAL sobre o relaxamento induzido com inibidores seletivos de PDE-3 (milrinona, seletiva para AMPc) e PDE-5 (sildenafila, seletiva para GMPc), sendo que FGAL só potencializou o relaxamento induzido por sildenafila, sugerindo a participação do GMPc. Como os canais de K+ são modulados negativamente pela PKC, investigou-se uma possível inibição da PKC por FGAL, que relaxou a aorta pré-contraída com o ativador de PKC (PMA), sugerindo inibição dessa enzima. Em conclusão, o mecanismo de ação espasmolítica de FGAL em traqueia envolve modulação positiva dos SKCa e dos nucleotídios cíclicos, e em aorta modulação positiva dos KATP, SKCa, Kir, KV; inibição dos CaV e dos ROCs, da liberação de Ca2+ do RS, da PDE-5 e PKC.

Made available in DSpace on 2015-05-14T12:59:34Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3371563 bytes, checksum: 0f72f1a088caa63b4cd2bf4057752d08 (MD5) Previous issue date: 2012-02-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This work describes the results of phytochemical studies from three species of the Erythroxylum genus: Erythroxylum caatingae Plowman, Erythroxylum subrotundum A. St.-Hil and Erythroxylum revolutum Mart, which were identified by the botany sector of the Laboratory of Pharmaceutical Technology, UFPB. The species were submitted to extraction process, followed by partition with hexane, chloroform and ethyl acetate, resulting in their respective phases. Four Tropane alkaloids were isolated by chromatography methods from the chloroformic phase of Erythroxylum caatingae, in which two were already isolated [3α, 6β dibenzoyloxytropane and 3α-(3 ,4 ,5 - trimethoxybenzoiloxi)-6β-benzoyloxytropane (Catuabine B)] and the other two were reported for the first time in the literature [3-(3 ,4 -dimethoxy)-6-hydroxytropane and 3α-(trans-3 ,4 ,5 trimethoxycinnamoyloxy)-6β-benzoyloxytropane]. From the ethyl acetate phase of Erythroxylum subrotundum, two flavonoids were isolated: Quercetin-3-O-α-L-rhamnoside and 5,7,4 -trihydroxyflavone-3-O-α-L-rhamnoside. The study of the Erythroxylum revolutum hexanic phase resulted in the isolation of six diterpenes: ent-kauran-16-ene, 13-hydroxy-8(17),14-labdadien (Manool), ent-kaur-16- en-3β-ol, 3-oxo-13-hydroxi-8(17),14-labdadien, 3,13,19-trihydroxy-8(17),14-labdadien and ent-kauran-16β, 17-diol. All the species had their chemical constituents identified through data analysis obtained from spectroscopic methods such as Infrared and Nuclear Magnetic Resonance of 1H and 13C with uni-bidimensional techniques, besides comparison with literature data. Therefore, the given results of this work contributed to the chemical study of the species from Erythroxylaceae family. / Este trabalho descreve os resultados dos estudos fitoquímicos de três espécies do gênero Erythroxylum: Erythroxylum caatingae Plowman, Erythroxylum subrotundum A. St.- Hil e Erythroxylum revolutum Mart, identificadas pelo setor de botânica do Laboratório de Tecnologia Farmacêutica da UFPB. As espécies foram submetidas a processos de extração e posterior particionamento de seus extratos resultando nas fases hexânica, clorofórmica e acetato de etila. Do estudo da fase clorofórmica de Erythroxylum caatingae foram isolados, através de métodos cromatográficos, quatro alcaloides tropânicos, sendo dois destes alcaloides [3α,6β dibenzoiloxitropano e 3α-(3 ,4 ,5 - trimetoxibenzoiloxi)-6β-benzoiloxitropano (Catuabina B)], já isolados anteriormente e dois alcalóides inéditos na literatura [3-(3 ,4 -dimetoxi)-6-hidroxitropano e 3α- (trans-3 ,4 ,5 trimetoxicinamoiloxi)-6β-benzoiloxitropano]. Da fase acetato de etila de Erythroxylum subrotundum foram isolados dois flavonoides: a Quercetina-3-O-α-Lraminosídeo e 5,7,4 -trihidroxiflavona-3-O-α-L-raminosídeo. Do estudo da fase hexânica de Erythroxylum revolutum foram isolados seis diterpenos: ent-cauran-16-eno, 13-hidroxi-8(17),14-labdadieno (Manool), ent-caur-16-en-3β-ol, 3-oxo-13-hidroxi- 8(17),14-labdadieno, 3,13,19-trihidroxi-8(17),14-labdadieno e ent-cauran-16β, 17-diol. As espécies tiveram seus constituintes químicos identificados através da análise de dados obtidos por métodos espectroscópicos como Infravermelho e Ressonância Magnética Nuclear de 1H e 13C uni-bidimensional, além de comparação com dados obtidos na literatura. Assim, os resultados obtidos neste trabalho contribuíram para o estudo químico de espécies da família Erythroxylaceae.

Made available in DSpace on 2015-05-14T12:59:45Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2667154 bytes, checksum: 834d9ddbecedbaa8447a53308ea82294 (MD5) Previous issue date: 2009-11-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Piptadenia stipulaceae belonging to the Fabaceae family, one of the largest in dicots and the third largest family of flowering plants. This species is commonly known in the Brazilian Northeast as mimosa white, carcara, calumbi and is widely distributed in the caatinga, and is used in folk medicine in inflammation. This paper describes the isolation and structural identification of some chemical constituents of aerial parts of Piptadenia stipulacea (Benth.) Ducke, in order to increase knowledge about the chemical Piptadenia genus, and provide samples for testing to confirm the pharmacological popular use of the species. The chemical constituents were identified through analysis of data obtained by spectroscopic methods such as Infrared Spectroscopy and 1H and 13C Nuclear Magnetic Resonance uni-dimensional, and compared with literature values. Phytochemical study of the chloroform extract of P. stipulacea resulted in the isolation of five flavonoids: 5-7-dihydroxy-3,4 ,6- trimethoxyflavone; 4 ,5,7-trihydroxy-3,3 ,6-trimethoxyflavone; 4 ,5,7- trihydroxy-3 ,6- dimethoxyflavone, first reported in the genus, 3,3 ,5,7-tetrahydroxy-4 ,6- dimethoxyflavone and 4',5,7-trihydroxy-3,6-dimethoxyflavone, first described in the family. / Piptadenia stipulaceae pertencente a família Fabaceae, uma das maiores em dicotiledôneas e a terceira maior família das angiospermas. Esta espécie é conhecida vulgarmente no Nordeste brasileiro como jurema branca, carcará, calumbi e apresenta ampla distribuição na caatinga nordestina, sendo utilizada na medicina popular nas inflamações. O presente trabalho descreve o isolamento e a identificação estrutural de alguns constituintes químicos das partes aéreas de Piptadenia stipulacea (Benth) Ducke, com o objetivo de ampliar o conhecimento químico sobre o gênero Piptadenia, bem como disponibilizar amostras para a realização de ensaios farmacológicos que confirmem o uso popular da espécie. Os constituintes químicos foram identificados através da análise de dados obtidos por métodos espectroscópicos como IV e RMN de 1H e 13C uni e bidimensionais, além de comparação com valores da literatura. O estudo fitoquímico da fase clorofórmica de P. stipulacea resultou no isolamento de cinco flavonóides: 5-7-diidroxi-3,4 ,6- trimetoxiflavona; 4 ,5,7-triidroxi-3,3 ,6-trimetoxiflavona; 4 ,5,7-triidroxi-3 ,6- dimetoxiflavona, relatados pela primeira vez no gênero, 3,3 ,5,7-tetraiidroxi-4 ,6- dimetoxiflavona e 4',5,7-triidroxi-3,6-dimetoxiflavona, descritos pela primeira vez na família.