RESUMO
OBJECTIVE: Ginger (Zingiber officinale Roscoe) is considered to be one of the most commonly consumed dietary condiments of the world. The present study was designed to explicate the protective role of zingerone; an active ingredient of ginger in complete Freund's adjuvant (FCA)-immunized arthritic rats. METHODS: 24 Wistar rats were divided into 4 groups with 6 rats each. Group I as control followed by group II, III and IV were treated with single intradermal injection of FCA (0.1â ml = 100â µg) to induce rheumatoid arthritis. Group III and IV were also administered with zingerone orally at 25â mg/kg b.w for 3 weeks at two different time points. RESULTS: Adjuvant-treated rats exhibited a significant increase in lipid peroxidation and a reduction in the enzymatic antioxidants such as SOD, catalase and GPx, in the liver and joint tissues. Moreover, FCA inoculation resulted in the increase in levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and a decrease in IL-10 levels. Zingerone significantly reduced the levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and markedly increased IL-10 levels. Levels of antioxidant enzymes were also restored by zingerone treatment. DISCUSSION: Oral administration of zingerone ameliorated inflammatory outburst and decreased oxidative stress, suggesting its role in the prevention of rheumatoid arthritis. Further mechanistic insights are necessary to study the exact mechanism involved.
Assuntos
Antioxidantes , Artrite Reumatoide , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Butanos , Citocinas , Guaiacol/análogos & derivados , Ratos , Ratos WistarRESUMO
Pioglitazone (PGZ) is an oral antidiabetic agent that increases cell resistance to insulin, thereby decreasing blood glucose levels. PGZ is a class II drug. Because of its pH-dependent solubility, it precipitates at the intestinal pH, resulting in an erratic and incomplete absorption following oral administration, which causes fluctuations in its plasma concentration. A nanoparticle drug delivery system offers a solution to enhance the dissolution rate of this poorly water-soluble drug. PGZ nanoparticles were formulated by the wet milling technique using a planetary ball mill. The effects of the steric stabilizer (Pluronic F-127, PL F-127), electrostatic stabilizer (sodium deoxycholate, SDC), and number of milling cycles were optimized using a Box-Behnken factorial design. The results showed that the ratio of PL F-127: SDC significantly affected the zeta potential and the dissolution efficiency (DE%) of PGZ. The optimized PGZ nanoparticle formulation enhanced the dissolution to reach 100% after 5 min. The in-vivo results showed significant enhancement in Cmax (1.3-fold) compared to that of the raw powder, and both AUC0-24 and AUC0-∞ were significantly (p < 0.05) enhanced. In conclusion, PGZ nanoparticle formulation had enhanced dissolution rate in the alkaline media, which improved its drug bioavailability relative to that of the untreated drug.
Assuntos
Química Farmacêutica/métodos , Hipoglicemiantes/síntese química , Nanopartículas/química , Pioglitazona/síntese química , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Estabilidade de Medicamentos , Hipoglicemiantes/farmacocinética , Masculino , Nanopartículas/metabolismo , Pioglitazona/farmacocinética , Distribuição Aleatória , Ratos , Ratos Wistar , Difração de Raios X/métodosRESUMO
The intent of this study was to utilize distillation timeframes (DT) of nutmeg (Myristica fragrans) essential oil (EO) to generate fractions with differential chemical compositions and bioactivity. Ten fractions were captured at the following distillation timeframes: 0.0-0.5, 0.5-1.0, 1.0-2.5, 2.5-5.0, 5.0-10, 10-30, 30-60, 60-90, 90-120, and 120-240 min. In addition, a control EO was collected from a straight 0-240 min non-stop distillation. ANOVA and advanced regression modeling revealed that the produced EO fractions possess substantial variation in the concentration of potentially desired compounds. The concentrations (%) of α-phellandrene, 3-carene, p-cymene, limonene, α-thujene, α-pinene, camphene, sabinene, ß-pinene, and myrcene decreased, while the concentrations (%) of α-terpinene, γ-terpinene, terpinolene, and myristicin increased in later DT fractions. Nutmeg EO showed some antimalarial activity against Plasmodium falciparum D6, but did not exhibit significant antifungal activity. In general, nutmeg seed oil yields increased with an increase of DT. These results may be utilized by industries using nutmeg EO.
Assuntos
Antimaláricos/química , Myristica/química , Óleos Voláteis/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/farmacologia , Cromatografia Gasosa , Destilação , Óleos Voláteis/farmacologia , Óleos de Plantas/análise , Óleos de Plantas/química , Sementes/químicaRESUMO
Stevia rebaudiana and its diterpene glycosides are one of the main focuses of food companies interested in developing novel zero calorie sugar substitutes since the recognition of steviol glycosides as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration. Rebaudioside A, one of the major steviol glycosides of the leaves is more than 200 times sweeter than sucrose. However, its lingering aftertaste makes it less attractive as a table-top sweetener, despite its human health benefits. Herein, we report the purification of two novel tetra-glucopyranosyl diterpene glycosides 1 and 3 (rebaudioside A isomers) from a commercial Stevia rebaudiana leaf extract compounds, their saponification products compounds 2 and 4, together with three known compounds isolated in gram quantities. Compound 1 was determined to be 13-[(2-O-ß-d-glucopyranosyl-6-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid-ß-d-glucopyranosy ester (rebaudioside Z), whereas compound 3 was found to be 13-[(2-O-ß-d-glucopyranosyl-3-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid -ß-d-glucopyranosy ester. Two new tetracyclic derivatives with no sugar at position C-19 were prepared from rebaudiosides 1 and 3 under mild alkaline hydrolysis to afford compounds 2 13-[(2-O-ß-d-glucopyranosyl-6-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid (rebaudioside Z1) and 4 13-[(2-O-ß-d-glucopyranosyl-3-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid. Three known compounds were purified in gram quantities and identified as rebaudiosides A (5), H (6) and J (7). Chemical structures were unambiguously elucidated using different approaches, namely HRESIMS, HRESI-MS/MS, and 1D-and 2D-NMR spectroscopic data. Additionally, a high-quality crystal of iso-stevioside was grown in methanol and its structure confirmed by X-ray diffraction.
Assuntos
Diterpenos/química , Extratos Vegetais/química , Stevia/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Glicosilação , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Enteric septicemia of catfish, columnaris disease and streptococcosis, caused by Edwardsiella ictaluri, Flavobacterium columnare and Streptococcus iniae, respectively, are the most common bacterial diseases of economic significance to the pond-raised channel catfish Ictalurus punctatus industry. Certain management practices are used by catfish farmers to prevent large financial losses from these diseases such as the use of commercial antibiotics. In order to discover environmentally benign alternatives, using a rapid bioassay, we evaluated a crude extract from the roots of muscadine Vitis rotundifolia against these fish pathogenic bacteria and determined that the extract was most active against F. columnare. Subsequently, several isolated compounds from the root extract were isolated. Among these isolated compounds, (+)-hopeaphenol (2) and (+)-vitisin A (3) were found to be the most active (bacteriostatic activity only) against F. columnare, with 24-h 50% inhibition concentrations of 4.0 ± 0.7 and 7.7 ± 0.6 mg/L, respectively, and minimum inhibitory concentrations of 9.1 ± 0 mg/L for each compound which were approximately 25X less active than the drug control florfenicol. Efficacy testing of 2 and 3 is necessary to further evaluate the potential for these compounds to be used as antibacterial agents for managing columnaris disease.
Assuntos
Antibacterianos/uso terapêutico , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Vitis/química , Animais , Antibacterianos/química , Bioensaio , Peixes-Gato , Edwardsiella ictaluri/efeitos dos fármacos , Edwardsiella ictaluri/patogenicidade , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Flavobacterium/efeitos dos fármacos , Flavobacterium/patogenicidade , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Streptococcus iniae/efeitos dos fármacos , Streptococcus iniae/patogenicidadeRESUMO
Piliostigma thonningii (Schumach.) Milne-Redhead. (Leguminosae) is used for various medicinal purposes in African countries. Phytochemical investigation of P. thonningii yielded two compounds newly isolated from natural sources, 2ß-methoxyclovan-9α-ol (1), and methyl-ent-3ß-hydroxylabd-8(17)-en-15-oate (2), along with 14 known compounds (3-16). Compounds 1 and 4 (alepterolic acid) showed potential selectivity towards Trypanosoma brucei brucei with IC50 7.89 and 3.42 µM, respectively. Compound 2 showed activity towards T. brucei and Leishmania donovani Amastigote with IC50 3.84 and 7.82 µM, respectively. The structure activity relationship (SAR) of the isolated metabolites suggested that hydroxylation at C-2 enhances the antiprotozoal activity towards T. brucei in sesquiterpenes 1 and 3. Similarly hydroxylation at C-3 in labdane diterpenes elevates the antiprotozoal activity towards T. brucei.
RESUMO
In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 µg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 µg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-µg group than in the 44-µg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 µg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.
Assuntos
Imunossupressores/uso terapêutico , Pan-Uveíte/tratamento farmacológico , Sirolimo/uso terapêutico , Uveíte Intermediária/tratamento farmacológico , Uveíte Posterior/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Injeções IntravítreasRESUMO
Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds (I-IV) along with eleven known compounds (V-XV). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with δ and µ opioid receptors (-49.7 and -53.8% displacement, resp.). Compound I was found to be possibly allosteric for κ and µ opioid receptors (-88.4 and -27.2% displacement, resp.) and showed moderate activity (60.5% displacement) towards CB1 receptor. Compound II exhibited moderate activity towards cannabinoid receptors CB1 and CB2 (47.9 and 42.3% displacement, resp.). The known compounds (V-VIII) exhibited prominent activity towards cannabinoid receptors: pomiferin (V) (IC50 of 2.110 and 1.318 µM for CB1 and CB2, resp.), auriculasin (VI) (IC50 of 8.923 µM for CB1), warangalone (VII) (IC50 of 1.670 and 4.438 µM for CB1 and CB2, resp.), and osajin (VIII) (IC50 of 3.859 and 7.646 µM for CB1 and CB2, resp.). The isolated compounds were also tested for inhibition of human monoamine oxidase-A and monoamine oxidase-B enzymes activities, where all the tested compounds showed fewer inhibitory effects on MAO-A compared to MAO-B activities: auriculasin (VI) (IC50 of 1.91 and 45.98 µM for MAO-B and MAO-A, resp.).
RESUMO
Neuropathic pain is a worldwide health problem with no consensus regarding its optimal therapy. This study compared the analgesic effect and gastric, hepatic, and renal safety of combined low doses of diclofenac and celecoxib with gabapentin versus their individual high doses in the treatment of neuropathic pain in rats. Left sciatic nerve ligation was used as neuropathic pain model. Rats were allocated into 7 groups (7 rats for each): sham control; model group (received vehicle); Gaba-group (received gabapentin (100â¯mg/kg /day); Diclo 10-group (received diclofenac (10â¯mg/kg); Cele 10-group (received celecoxib (10â¯mg/kg/day); Gabaâ¯+â¯Diclo 5 (receivedgabapentin(100â¯mg/kg /day) plus diclofenac (5â¯mg/kg); Gabaâ¯+â¯Cele 5 (received gabapentin (100â¯mg/kg/day) plus celecoxib (5â¯mg/kg)). The analgesic effect was assessed using both hot plate and acetone tests. The impact of the used drugs on peptic ulcer index, liver enzymes, and serum urea and creatinine was evaluated, along with histopathological examination and oxidative stress parameters. Combination therapy of low dose of either diclofenac or celecoxib, with gabapentin showed higher analgesic effect compared with their individual high doses as indicated by prolonged response time in hot plate test and decreased frequency of paw withdrawal in acetone test. Their effect was associated with gentle effect on gastric mucosa, renal and hepatic integrity and oxidative stress parameters. In conclusion, the use of combined low doses of either diclofenac or celecoxib with gabapentin is better than high dose monotherapy regarding both the efficacy and safety.
Assuntos
Aminas/uso terapêutico , Analgésicos/uso terapêutico , Celecoxib/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Diclofenaco/uso terapêutico , Neuralgia/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêutico , Aminas/administração & dosagem , Aminas/efeitos adversos , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Animais , Comportamento Animal/efeitos dos fármacos , Celecoxib/administração & dosagem , Celecoxib/efeitos adversos , Ácidos Cicloexanocarboxílicos/administração & dosagem , Ácidos Cicloexanocarboxílicos/efeitos adversos , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Gabapentina , Masculino , Estresse Oxidativo/efeitos dos fármacos , Medição da Dor , Limiar da Dor , Ratos Wistar , Resultado do Tratamento , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/efeitos adversosRESUMO
Green tea (GT)-derived catechins; epigallocatechin gallate (EGCG) in particular are commonly used nutraceuticals for their free-radical scavenging activity (FRSA). The influence of photodegradation on the protective power of GT nutracenticals against oxidative stress was thoroughly explored. Photodegradation of GT extracts was carried out and monitored using orthogonal stability-indicating testing protocol; in vitro and in vivo assays. Total polyphenol content (TPC) and FRSA were determined spectrophotometrically while EGCG was selectively monitored using SPE-HPLC. In vivo assessment of photodegraded samples was investigated via measuring a number of biomarkers for hepatic oxidative stress and apoptosis (caspase-3, inducible nitric oxide synthase, nitric oxide, mitogen-activated protein kinase, glutathione, thiobarbituric acid reactive substances, nuclear factor kappa beta, and nuclear factor erythroid 2-related factor) as well as liver damage (alanine transaminase and aspartate transaminase) in serum of rats previously subjected to oxidative stress. Results showed complete degradation of EGCG in photodegraded green tea samples with no correlation with either TPC or FRSA. On the other hand, in vivo assay results revealed not only loss of activity but formation of harmful pro-oxidants. Photostability was found crucial for the protective effect of GT extract against lead acetate insult. Results confirmed that careful design of quality control protocols requires correlation of chemical assays to bioassays to verify efficacy, stability, and most importantly safety of nutraceuticals.
Assuntos
Antioxidantes/farmacologia , Camellia sinensis/química , Catequina/farmacologia , Suplementos Nutricionais , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Chá/química , Animais , Antioxidantes/análise , Aspartato Aminotransferases/metabolismo , Catequina/análogos & derivados , Catequina/análise , Glutationa/metabolismo , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/análise , Polifenóis/farmacologia , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
BACKGROUND: A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using an in vitro anti-malarial screening platform to identify known or new natural products for lead development. The platform identifies hits on the basis of in vitro growth inhibition of Plasmodium falciparum and counter-screens for cytotoxicity to human foreskin fibroblast or embryonic kidney cell lines. The physical library was supplemented by early-stage collection of analytical data for each fraction to aid rapid identification of the active components within each screening hit. RESULTS: A total of 16,177 fractions from 1300 plants were screened, identifying several P. falciparum inhibitory fractions from 35 plants. Although individual fractions were screened for bioactivity to ensure adequate signal in the analytical characterizations, fractions containing less than 2.0 mg of dry weight were combined to produce combined fractions (COMBIs). Fractions of active COMBIs had EC50 values of 0.21-50.28 and 0.08-20.04 µg/mL against chloroquine-sensitive and -resistant strains, respectively. In Berberis thunbergii, eight known alkaloids were dereplicated quickly from its COMBIs, but berberine was the most-active constituent against P. falciparum. The triterpenoids α-betulinic acid and ß-betulinic acid of Eugenia rigida were also isolated as hits. Validation of the anti-malarial discovery platform was confirmed by these scaled isolations from B. thunbergii and E. rigida. CONCLUSIONS: These results demonstrate the value of curating and exploring a library of natural products for small molecule drug discovery. Attention given to the diversity of plant species represented in the library, focus on practical analytical data collection, and the use of counter-screens all facilitate the identification of anti-malarial compounds for lead development or new tools for chemical biology.
Assuntos
Antimaláricos/farmacologia , Produtos Biológicos/farmacologia , Extratos Vegetais/farmacologia , Plantas/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Humanos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidadeRESUMO
Eschscholzia californica, a native US plant, is traditionally used as a sedative, analgesic, and anxiolytic herb. With the rapid rise in the use of herbal supplements together with over-the-counter and prescription drugs, the risk for potential herb-drug interactions is also increasing. Most of the clinically relevant pharmacokinetic drug interactions occur due to modulation of cytochrome P450 enzymes (CYPs), P-glycoprotein, and the pregnane X receptor by concomitantly used herbs. This study aimed to determine the effects of an EtOH extract, aqueous extract (tea), basic CHCl3 fractions, and isolated major alkaloids, namely protopine (1), escholtzine (2), allocryptopine (3), and californidine (4), of E. californica on the activity of cytochrome P450s, P-glycoprotein and the pregnane X receptor. The EtOH extract and fractions showed strong time-dependent inhibition of CYP 3A4, CYP 2C9, and CYP 2C19, and reversible inhibition of CYP 2D6. Among the alkaloids, escholtzine (2) and allocryptopine (3) exhibited time-dependent inhibition of CYP 3A4, CYP 2C9, and CYP 2C19 (IC50 shift ratio > 2), while protopine (1) and allocryptopine (3) showed reversible inhibition of CYP 2D6 enzyme. A significant activation of the pregnane X receptor (> 2-fold) was observed with the EtOH extract, basic CHCl3 fraction, and alkaloids (except protopine), which resulted into an increased expression of mRNA and the activity of CYP 3A4 and CYP 1A2. The expression of P-glycoprotein was unaffected. However, aqueous extract (tea) and its main alkaloid californidine (4) did not affect cytochrome P450s, P-glycoprotein, or the pregnane X receptor. This data suggests that EtOH extract of E. californica and its major alkaloids have a potential of causing interactions with drugs that are metabolized by cytochrome P450s, while the tea seems to be safer.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Alcaloides/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Eschscholzia/química , Receptores de Esteroides/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Benzofenantridinas/farmacologia , Alcaloides de Berberina/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Dioxóis/farmacologia , Cães , Células Hep G2/efeitos dos fármacos , Interações Ervas-Drogas , Humanos , Células Madin Darby de Rim Canino/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptor de Pregnano X , Receptores de Esteroides/genéticaRESUMO
A set of diphenyl ether derivatives bearing different heterocycles were synthesized from 4-phenoxybenzohydrazide 1 in good yield. Synthesized compounds were screened against a broad panel of viruses in different cell cultures and some of the synthesized compounds showed promising antiviral properties.
Assuntos
Compostos de Bifenilo/síntese química , Compostos de Bifenilo/farmacologia , Éter/síntese química , Éter/farmacologia , Vírus/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Bioensaio , Compostos de Bifenilo/química , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Éter/química , Humanos , Modelos Moleculares , Estrutura Molecular , Pirazóis/química , Pirazóis/farmacologia , Piridinas/química , Piridinas/farmacologiaRESUMO
Vitamin D is claimed to have an adjuvant effect on glycemic control by dual action on pancreatic ß-cells and insulin resistance. The aim of this study was to assess the possible effect of short-term alfacalcidol supply on glycemic control in type 2 diabetic hemodialysis (HD) patients. Twenty type 2 diabetic HD patients (using diet and oral drugs but not insulin) were randomly selected from our dialysis unit as well as 20 non-diabetic HD patients as control. A third group of 12 healthy subjects were studied as well. All three groups were similar in age, sex, and body mass index. Oral alfacalcidol therapy was administrated daily as recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for 12 weeks guided by monthly serum phosphorus and Cax PO4 product. Corrected total calcium, phosphorus, intact parathyroid hormone, 25-hydroxy vitamin D (25[OH]D), and glucoparameters (fasting blood glucose, glycated hemoglobin [HbA1c%], insulin resistance by homeostatic model assessment, and ß-cell function by HOMA-ß%) were measured under basal conditions and after 3 months of therapy. 25(OH)D was non-significantly lower in diabetic than non-diabetic HD patients, but significantly lower than healthy subjects at the start of the study. However, vitamin D level increased significantly after 3 months of trial, although the levels did not reach normal values. This vitamin D rise was associated with highly significant improvement in concentrations of fasting blood sugar (FBS), fasting insulin, HbA1c%, and HOMA-ß-cell function in diabetic and non-diabetic controls. However, there was a significant rise in insulin resistance after treatment. The percentage of change was evident more in diabetics regarding FBS and 25(OH)D concentration. Adjustment of 25(OH)D level in type 2 diabetic prevalent HD patients may improve, at least with short-term therapy, glycemic control mainly through improving ß-cell function.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais/análise , Diálise Renal/métodos , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/administração & dosagem , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
Epigallocatechin gallate (EGCG) is a powerful antioxidant and commonly used nutraceutical. Accelerated stability of EGCG in tablet formulations was investigated. LLE and SPE were employed for sample clean-up and enrichment of EGCG over caffeine. Samples were analysed after spiking with fixed concentration of gallic acid (GA), in order to verify reproducibility of analysis. A TLC-densitometric assay was developed and validated for determination of % loss EGCG. EGCG, GA and caffeine were resolved with Rf values 0.54, 0.69 and 0.80, respectively. LC-MS/MS was used to verify identity and purity of the EGCG band. Determination was carried out over a concentration range of 0.50-5.00µg/band and 0.20-2.40µg/band for GA and caffeine, respectively. Results showed significant reduction in EGCG content after one, three and six months: 24.00%, 28.00% and 52.00% respectively. Results continue to demonstrate that stability of nutraceutical products should be investigated in-depth using industry-oriented protocols before granting marketing authorisation.
Assuntos
Camellia sinensis/química , Catequina/análogos & derivados , Suplementos Nutricionais/análise , Extratos Vegetais/química , Chá/química , Catequina/química , Catequina/isolamento & purificação , Cromatografia em Camada Fina/métodos , Espectrometria de Massas , Extratos Vegetais/isolamento & purificação , Extração em Fase Sólida/métodosRESUMO
Two new pentacyclic ingamine alkaloids, namely 22(S)-hydroxyingamine A (2) and dihydroingenamine D (3), together with the known ingamine A (1), have been isolated from marine sponge Petrosid Ng5 Sp5 (family Petrosiidae) obtained from the open repository of the National Cancer Institute, USA. The structures of compounds 1-3 were determined using 1D and 2D NMR, and HRESIMS techniques. The absolute configuration of both the C9 and C22 of 2 was determined as (S) using a modified Mosher esterification method. Compounds 1 and 3 showed strong antiplasmodial activity against chloroquine-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum with IC50 values of 90 and 78 ng/mL and 72 and 57 ng/mL, respectively, while 2 was found to be less active (IC50 values of 200 and 140 ng/mL, respectively). Compounds 1-3 were found to be devoid of in vitro cytotoxicity against human solid tumor cells of breast (BT-549), ovary (SK-OV-3), and epidermoid (KB) carcinomas and skin melanoma (SK-MEL), as well as against noncancerous monkey kidney fibroblasts (VERO) and pig kidney epithelial (LLC-PK11) cells, up to a maximum concentration of 10 µg/mL. Compounds 1-3 also displayed weak antimicrobial and moderate antileishmanial activities against Leishmania donovani promastigotes. These polycyclic ingamine alkaloids represent the first example of antiplasmodial leads without a ß-carboline ring, which is known to be responsible for the cytotoxicity of the well-known manzamine class of marine alkaloids related to 1-3.