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1.
PLoS One ; 16(10): e0258265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614022

RESUMO

Five groups of lambs (n = 9 each) were used to test the effect of plant extracts rich in hydrolysable (HT) or condensed tannin (CT) on animal performance, fatty acid composition of rumen content, liver and meat. The control group (CO) received a concentrate-based diet without tannins supplementation. The other groups received the same diet as the control lambs plus 4% chestnut (CH) and tara (TA) extracts as a source of HT and mimosa (MI) and gambier (GA) extracts as a source of CT. One-way ANOVA was used to assess the overall effect of dietary treatments, tannins supplementation (CO vs. CH+TA+MI+GA) and the effect of tannin type (HT vs. CT: CH+TA vs. MI+GA) on animal performance, rumen content, liver and intramuscular FA. Dietary CH negatively affected animal performance. The rumen content of the different groups showed similar levels of 18:3 c9c12c15, 18:2 c9c12, 18:2 c9t11, 18:1 t11 and 18:0, whereas 18:1 t10 was greater in CO. Also, 18:1 t10 tended to be lower in the rumen of HT than CT-fed lambs. These data were partially confirmed in liver and meat, where CO showed a greater percentage of individual trans 18:1 fatty acids in comparison with tannins-fed groups. Our findings challenge some accepted generalizations on the use of tannins in ruminant diets as they were ineffective to favour the accumulation of dietary PUFA or healthy fatty acids of biohydrogenation origin in the rumen content and lamb meat, but suggest a generalized influence on BH rather than on specific steps.


Assuntos
Suplementos Nutricionais , Ácidos Graxos/metabolismo , Taninos Hidrolisáveis/farmacologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Ovinos/metabolismo , Animais , Análise Discriminante , Fígado/metabolismo , Carne/análise , Análise Multivariada
2.
J Agric Food Chem ; 69(37): 11053-11064, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34495660

RESUMO

Aronia melanocarpa (MICHX.) ELLIOTT, which belongs to the Rosaceae family, has increasingly come into focus of research due to the high content of polyphenols. In addition to antioxidative properties, further health-promoting effects of these polyphenols are still of interest. Especially, the proanthocyanidins offer thereby huge opportunities due to their high structural heterogeneity. Therefore, the present study focuses on the topoisomerase inhibiting effects of oligomeric proanthocyanidins (PACs), which are potentially depended on their degree of polymerization. The investigated PACs isolated from Aronia berries were characterized by chromatographic techniques and liquid chromatography-high-resolution mass spectrometry. Four PAC enriched fractions were obtained from Aronia pomace containing 47 PACs with a degree of polymerization from three to six. Due to the low yield of hexamers, the potential inhibiting effects against human topoisomerase were investigated for the trimer to pentamer fractions. The relaxation and decatenation assays were performed to examine the inhibiting effect on topoisomerases under cell-free conditions. Moreover, rapid isolation of topoisomerase cleavage complexes in human colon carcinoma HT29 cells was performed to evaluate the effect on topoisomerases in a cell-based system. The fractions demonstrated inhibitory potential on topoisomerases I and II. In sum, an increasing effect strength depending on the degree of polymerization was shown.


Assuntos
Photinia , Proantocianidinas , Rosaceae , Frutas , Humanos , Espectrometria de Massas , Extratos Vegetais/farmacologia , Polifenóis , Proantocianidinas/farmacologia
3.
Ecotoxicol Environ Saf ; 223: 112586, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364126

RESUMO

The functional role of procyanidins (PC) in PM2.5-induced cardiovascular diseases (CVD) is largely unexplored. This study aimed to explore the protective effect of PC against PM2.5-induced vascular smooth muscle cells (VSMCs) apoptosis and underlying mechanisms. Sprague Dawley rats were pretreated with three doses of PC (50, 100, and 200 mg/kg) and exposed to 10 mg/kg PM2.5 by intratracheal instillation three times a week. VSMCs were exposed to 5, 10, and 20 µM PC before the addition of 100 µg/mL PM2.5. In vivo, the PM2.5 exposure induced apoptosis in the thoracic aorta of rats. The PM2.5 exposure significantly elevated the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and decreased the superoxide dismutase activity. Also, PC supplementation increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), and its downstream antioxidant genes, i.e., NAD(P)H dehydrogenase (quinine) 1 and heme oxygenase 1, attenuated oxidative stress and vascular apoptosis. In vitro, PM2.5 induced cytotoxicity in VSMCs in a dose-dependent manner. Besides, PC abolished the PM2.5-induced cytotoxicity by activating the Nrf2 signal pathway, alleviating oxidative stress, and decreasing apoptosis. In conclusion, this work is the first study to demonstrate that PC can suppress the PM2.5-induced VSMCs apoptosis via the activation of the Nrf2 signal pathway.


Assuntos
Fator 2 Relacionado a NF-E2 , Proantocianidinas , Animais , Apoptose , Músculo Liso Vascular/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Material Particulado/metabolismo , Material Particulado/toxicidade , Proantocianidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
4.
Dent Mater ; 37(9): 1437-1445, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34353622

RESUMO

OBJECTIVE: This study evaluated the potential combined effects of nanohydroxyapatite and proanthocyanidin on the remineralization and collagen stabilization of demineralized dentin. METHODS: Seventy-five coronal dentin beams (6 × 1 × 1 mm3) were randomly allocated into five experimental groups (n = 15): Sound (no treatment), Control (pH-cycling), nHAp (nanohydroxyapatite), nHAp_PA (Proanthocyanidin-functionalized nanohydroxyapatite), and PA (proanthocyanidin) treatments. The sound group (negative control) were immersed in distilled water over the experimental period. The remaining groups were submitted to a pH-cycling process for 14 days. Following the de-re mineralization process, specimens corresponding to the control group (positive control) were immersed in distilled water whereas the test groups were immersed in 1 mL of respective solution treatment (nHAp, nHAp_PA, or PA) for 1 min. The dentin samples were analyzed to determine their chemical composition (ATR-FTIR and Thermogravimetric) and mineralogical (XRD) characteristics as well as their mechanical response, obtained by three-point bending test. RESULTS: Higher phosphate content (v4 PO4: ATR-FTIR) and amount of mineral (XRD) was observed in the nHAp_PA group. Furthermore, a larger induction of collagen cross-links (ATR-FTIR) and %Organic Matter (TGA) would indicate the PA incorporation and the achievement of dentin matrix stability. These effects on dentin properties were related to increasing flexural strength (MPa), demonstrating that 15% w/v nHAp_PA treatment improved the mechanical properties of the samples. SIGNIFICANCE: nHAp_PA shows significant potential for promoting remineralization while improving collagen stability into demineralized dentin in a clinically feasible period of 1 min.


Assuntos
Nanopartículas , Proantocianidinas , Colágeno , Dentina , Durapatita , Proantocianidinas/farmacologia
5.
J Biochem Mol Toxicol ; 35(9): e22845, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34338401

RESUMO

Diabetic retinopathy (DR) is a common diabetic complication known to cause vision impairment and blindness. Previous studies have demonstrated that proanthocyanidins (PACs), polyphenols that are naturally found in several plants and fruits, have powerful antioxidant and anti-inflammatory effects on various cells. However, the effects and underlying mechanism of PACs against DR pathogenesis remain unknown. Here, we investigated the proliferation, apoptosis, and mechanisms of ARPE-19 cells in response to oxidative stress and inflammation under high-glucose conditions with or without PACs treatment. The Cell-Counting Kit-8 assay and western blot analysis showed that treatment with 10 µl PACs significantly increased cell proliferation and the expression level of Bcl-2 in ARPE-19 cells under high-glucose conditions. Moreover, PACs attenuated the high glucose-induced apoptosis, and the increased expression levels of caspase-3 and Bax. Under high-glucose conditions, the generation of reactive oxygen species (ROS) and levels of malondialdehyde increased, whereas the superoxide dismutase content decreased. Moreover, the expression level of the NLRP3 inflammasome, and the release of interleukin 1ß (IL-1ß) and IL-18 increased. PACs reversed all of these high glucose-induced effects on ARPE-19 cells. Additionally, exposure to nigericin sodium salt, an agonist of the NLRP3 inflammasome, upregulated expression of the NLRP3 inflammasome accompanied by the release of IL-1ß and IL-18. Again, treatment with PACs markedly downregulated these effects. Collectively, these results demonstrate that PACs can prevent retinal pigment epithelial cells from high glucose-induced injury via inhibiting the generation of ROS and activation of the NLRP3 inflammasome, suggesting PACs as a potential candidate for the management of DR.


Assuntos
Células Epiteliais/metabolismo , Glucose/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/farmacologia , Epitélio Pigmentado da Retina/metabolismo , Linhagem Celular , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Células Epiteliais/patologia , Humanos , Epitélio Pigmentado da Retina/patologia
6.
Free Radic Biol Med ; 174: 144-156, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34389464

RESUMO

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent.


Assuntos
Extrato de Sementes de Uva , Proantocianidinas , Animais , Antioxidantes/farmacologia , Proteína Forkhead Box O1/genética , Extrato de Sementes de Uva/farmacologia , Células-Tronco Hematopoéticas , Camundongos , Proantocianidinas/farmacologia , Radiação Ionizante
7.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361744

RESUMO

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pinus/química , Prosencéfalo/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Flavonoides/química , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Gerbillinae , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação , Interleucina-13/agonistas , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-4/agonistas , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Fármacos Neuroprotetores/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Proantocianidinas/química , Proantocianidinas/farmacologia , Prosencéfalo/metabolismo , Prosencéfalo/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
Chem Pharm Bull (Tokyo) ; 69(11): 1039-1044, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34456215

RESUMO

Exposure to UV radiation damages the skin and increases the risk of skin cancer. Sunscreen is used to protect the skin from the harmful effects of UV radiation. However, the chemical UV filters used in sunscreen can show toxicity and cause allergic reactions. A safe sunscreen that includes a lower content of chemical UV filters and exerts an excellent effect on UV protection needs to be developed. The objective of this study was to investigate whether the addition of afzelin to sunscreen could improve the sun protection factor (SPF). A synergistic effect between afzelin and organic sunscreen agents including padimate O and oxybenzone was confirmed. Interestingly, 100% in vitro SPF-boosting was observed when afzelin (0.05%) was applied with a standard SPF formulation containing organic sunscreens while afzelin alone had no contribution to the SPF. In vivo SPF analysis of the standard SPF formulation showed an SPF value of 13.3 that increased to 20.1 when supplemented with afzelin (0.05%). Additionally, afzelin showed no skin irritation in a human trial. These results suggest that afzelin is useful as a natural additive in sunscreen formulations and provides an SPF-boosting effect. Afzelin supplementation to the formulation showed the potential to reduce the use of synthetic photoprotectors, which could minimize the risk of synthetic agent toxicity.


Assuntos
Cosméticos/química , Manosídeos/química , Proantocianidinas/química , Fator de Proteção Solar/métodos , Protetores Solares/química , Adolescente , Adulto , Benzofenonas/farmacologia , Ensaios Clínicos como Assunto , Cosméticos/farmacologia , Composição de Medicamentos , Feminino , Humanos , Masculino , Manosídeos/farmacologia , Pessoa de Meia-Idade , Proantocianidinas/farmacologia , Pele , Protetores Solares/farmacologia , Raios Ultravioleta , para-Aminobenzoatos/farmacologia
9.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198881

RESUMO

Euterpe oleracea Mart. (Arecaceae) is an endogenous palm tree from the Amazon region. Its seeds correspond to 85% of the fruit's weight, a primary solid residue generated from pulp production, the accumulation of which represents a potential source of pollution and environmental problems. As such, this work aimed to quantify and determine the phytochemical composition of E. oleracea Mart. seeds from purple, white, and BRS-Pará açaí varieties using established analytical methods and also to evaluate it as an eco-friendly corrosion inhibitor. The proanthocyanidin quantification (n-butanol/hydrochloric acid assay) between varieties was 6.4-22.4 (w/w)/dry matter. Extract characterization showed that all varieties are composed of B-type procyanidin with a high mean degree of polymerization (mDP ≥ 10) by different analytical methodologies to ensure the results. The purple açaí extract, which presented 22.4% (w/w) proanthocyanidins/dry matter, was tested against corrosion of carbon steel AISI 1020 in neutral pH. The crude extract (1.0 g/L) was effective in controlling corrosion on the metal surface for 24 h. Our results demonstrated that the extracts rich in polymeric procyanidins obtained from industrial açaí waste could be used to inhibit carbon steel AISI 1020 in neutral pH as an abundant, inexpensive, and green source of corrosion inhibitor.


Assuntos
Euterpe/química , Proantocianidinas/farmacologia , Aço/química , Corrosão , Química Verde , Extratos Vegetais/química , Proantocianidinas/química , Sementes/química
10.
Pestic Biochem Physiol ; 177: 104898, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34301360

RESUMO

Cypermethrin, a type II pyrethroid pesticide, is one of the most widely used pesticides in agricultural and in household settings. The toxic effects of cypermethrin are a matter of concern, as humans are almost inevitably exposed to it in daily life. It is an urgent problem to seek natural substances from plants that can eliminate or relieve the effects of pesticide residues on human health. Proanthocyanidins are the most potent antioxidants and free radical scavengers in natural plants, and are widely available in fruits, vegetables, and seeds. We found that proanthocyanidins (1, 2.5, and 5 µg/mL) can decrease ROS generation, relieve mitochondrial membrane potential loss, repair nuclear morphology, reduce cell apoptosis, and protect neurons from cypermethrin-induced oxidative insult. The protective mechanism exerted by proanthocyanidins against cypermethrin-induced neurotoxicity is negatively regulate rather than activate the Nrf2/ARE signaling pathway to maintain intracellular homeostasis.


Assuntos
Proantocianidinas , Piretrinas , Antioxidantes , Apoptose , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Proantocianidinas/farmacologia , Piretrinas/toxicidade , Transdução de Sinais
11.
Colloids Surf B Biointerfaces ; 206: 111941, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34216847

RESUMO

Aerogels based on gelatin and graphene oxide (GO) were synthesized by microwave-assisted reactions, incorporating grape skin extracts -high in proanthocyanidins (PAs)- to develop a hemostatic device with improved properties. The effects of incorporating PAs into the aerogels were investigated in relation to their physicochemical properties, absorption ability, clotting activity and cytotoxicity in human dermal fibroblast (HDF) cells. The aerogels presented highly resistant porous structures, capable of absorbing more than 50 times their weight when in contact with a phosphate saline solution (PBS) and fresh human blood. Interestingly, the addition of PAs increased the negative surface charges and the blood absorption ability of the aerogels, which may make them suitable for hemostasis. The incorporation of 5% and 10% (w/w) of extracts into the aerogels increased the total coagulated blood content by 36.6% and 24.5% compared with gelatin-GO aerogel, respectively. These improvements in the hemostatic properties of the aerogels were greater with the inclusion of 5% (w/w) of grape skin extracts into the aerogels. The aerogels were also able to adhere red blood cells onto their surfaces, which could favor the formation of stable fibrin networks to promote hemostasis. Their clotting activity suggested the activation of alternative routes based on complement coagulation systems. Finally, the aerogels were non-toxic for HDF cells and the PAs were successfully released from their matrices. Thus, gelatin-GO aerogels reinforced with PAs are promising as topical phytodrug delivery systems, with great potential for wound healing processes.


Assuntos
Grafite , Proantocianidinas , Bandagens , Gelatina , Humanos , Proantocianidinas/farmacologia
12.
Commun Biol ; 4(1): 896, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290357

RESUMO

Proanthocyanidins (PAC) are dietary compounds that have been extensively studied for beneficial health effects due to their anti-inflammatory properties. However, the structure-function relationships of PAC and their mode-of-action remain obscure. Here, we isolated a wide range of diverse PAC polymer mixtures of high purity from plant material. Polymer size was a key factor in determining the ability of PAC to regulate inflammatory cytokine responses in murine macrophages. PAC polymers with a medium (9.1) mean degree of polymerization (mDP) induced substantial transcriptomic changes, whereas PAC with either low (2.6) or high (12.3) mDP were significantly less active. Short-term oral treatment of mice with PAC modulated gene pathways connected to nutrient metabolism and inflammation in ileal tissue in a polymerization-dependent manner. Mechanistically, the bioactive PAC polymers modulated autophagic flux and inhibited lipopolysaccharide-induced autophagy in macrophages. Collectively, our results highlight the importance of defined structural features in the health-promoting effects of PAC-rich foods.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/imunologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Anti-Inflamatórios/química , Citocinas/imunologia , Inflamação/induzido quimicamente , Macrófagos/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Proantocianidinas/química , Células RAW 264.7
13.
Nutrients ; 13(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063322

RESUMO

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.


Assuntos
Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vitis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anticoagulantes/farmacologia , Anti-Hipertensivos/farmacologia , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hipertensão/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/metabolismo , Trombofilia/tratamento farmacológico , Vasodilatadores/farmacologia
14.
Molecules ; 26(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067571

RESUMO

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 µg/mL) or N-Acetyl-L-cysteine (NAC) (20 µM) for 24 h, and then incubated with 200 µM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 µM) or PCs (4, 8 or 16 µg/mL) in the absence or presence of 300 µM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.


Assuntos
Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Acetilcisteína/farmacologia , Animais , Elementos de Resposta Antioxidante , Antioxidantes/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator de Transcrição NF-E2/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo
15.
Chem Biodivers ; 18(8): e2100299, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34086421

RESUMO

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application.


Assuntos
Biflavonoides/química , Catequina/química , Biologia Computacional/métodos , Inibidores Enzimáticos/química , Magnoliopsida/química , Extratos Vegetais/química , Proantocianidinas/química , Amilases/antagonistas & inibidores , Amilases/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/química , Biflavonoides/isolamento & purificação , Biflavonoides/metabolismo , Biflavonoides/farmacologia , Catequina/isolamento & purificação , Catequina/metabolismo , Catequina/farmacologia , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Magnoliopsida/metabolismo , Testes de Sensibilidade Microbiana , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Casca de Planta/química , Casca de Planta/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Proantocianidinas/isolamento & purificação , Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Espectrometria de Massas por Ionização por Electrospray
16.
Int J Biol Macromol ; 183: 1067-1078, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33965498

RESUMO

Human islet amyloid polypeptide (hIAPP) is widely studied due to its close correlation with the pathogenic mechanism of type II diabetes mellitus (T2DM). Bioflavonoids have been used in the neurodegeneration and diabetes studies. However, the structure-activity relationship remains unclear in many of these compounds. In this work, we performed diverse biophysical and biochemical methods to explore the inhibition of procyanidine on hIAPP and compared with that on amyloid-ß (Aß) protein which is linked to Alzheimer's disease (AD). The procyanidine effectively inhibited the aggregation of hIAPP and Aß through hydrophobic and hydrogen bonding interactions, it dissolved the aged fibrils into nanoscale particles. The compound also ameliorated the cytotoxicity and the membrane leakage by reducing the peptide oligomerization. The procyanidine showed better binding affinity and inhibitory effects on peptide aggregation and upregulated the cell viability to hIAPP than to Aß, which could be a prospective inhibitor against hIAPP. This work also offered a possible strategy for T2DM and AD treatments.


Assuntos
Amiloide/metabolismo , Biflavonoides/farmacologia , Catequina/farmacologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Proantocianidinas/farmacologia , Doença de Alzheimer/metabolismo , Amiloide/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Humanos
17.
Food Chem ; 359: 129889, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33934030

RESUMO

The objective was to analyze the phenolic composition, antioxidant capacity, and physical characteristics of 10 blackcurrant cultivars, their juices, and the enzymatic inhibition of dipeptidyl peptidase-IV, α-amylase, α-glucosidase, nitric oxide synthase, and cyclooxygenase-2. Fruit masses ranged from 0.47 to 1.22 g and diameters from 7.42 to 14.42 mm. For the juices, pH ranged from 2.80 to 2.96, soluble solids from 11.33% to 17.5%, total acidity from 3.17 to 4.26 g/100 mL, and viscosity from 1.28 to 273.83 mPa·s. Total anthocyanins (TA) ranged from 1.81 to 5.48 mg eq cyanidin 3-O-glucoside/100 g, total polyphenols (TP) from 7.67 to 39.70 mg eq gallic acid/100 g, total condensed tannins from 3.24 to 7.76 g eq catechin/100 g, and antioxidant capacity from 219.24 to 499.26 µmol eq Trolox/100 g. Juices of the cultivars Coronet and Consort contained the highest levels of TA, TP, and antioxidants. Whistler cultivar contained high concentrations of major anthocyanins. Juices from all cultivars favorably inhibited the activities of enzymes used as surrogate biochemical markers for T2 diabetes and inflammation.


Assuntos
Antocianinas/análise , Antioxidantes/análise , Extratos Vegetais/farmacologia , Polifenóis/análise , Proantocianidinas/análise , Ribes/química , Antocianinas/farmacologia , Inibidores de Ciclo-Oxigenase 2/análise , Inibidores da Dipeptidil Peptidase IV/análise , Frutas/química , Sucos de Frutas e Vegetais/análise , Inibidores de Glicosídeo Hidrolases/análise , Óxido Nítrico Sintase/antagonistas & inibidores , Fenóis/análise , Extratos Vegetais/química , Polifenóis/farmacologia , Proantocianidinas/farmacologia , alfa-Amilases/antagonistas & inibidores
18.
J Food Sci ; 86(6): 2445-2456, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963549

RESUMO

The interactions between polysaccharides and phenolics in foods affect their physicochemical properties and bioactivity. Pectin and catechin/procyanidin present in plants ubiquitously and attracting more attentions for the potential health benefits. This work investigates the interactions between high methoxyl pectin and catechin/procyanidin in a simulative juice model using multiple microscopic and spectroscopic approaches and their influences on the antioxidant activity of phenolics were evaluated in the Caco-2 cells model. The results showed that pectin with either of phenolic compunds exhibited lower transmittance, zeta potential, viscosity, and larger particle size than it alone. The morphology of pectin complexes with either of phenolics under experimental conditions (pH = 3.5) was observed. The ΔH° (-6.821 kJ mol-1 ) and ΔS° (6.357×10-2  kJ mol-1 ) indicated that pectin interacts with procyanidin via electrostatic interaction, whereas hydrophobic interaction was the dominant drive force between pectin and catechin (ΔH° = 1.422 kJ mol-1 ; ΔS° = 13.048 × 10-2  kJ mol-1 ). The antioxidant activities of catechin/procyanidin decreased while binding with pectin based on indexes of glutathione peroxidase, total superoxide dismutase, total antioxidant capacity, and malondialdehyde. PRACTICAL APPLICATION: The findings of this work indicated that the physicochemical property of pectin and the antioxidant activity of catechin/procyanidin were influenced by the interactions between pectin and catechin/procyanidin in a simulative food system. This study provides insights into the molecular interactions between pectin and phenolics in a simulative food system.


Assuntos
Antioxidantes/farmacologia , Biflavonoides/farmacologia , Catequina/farmacologia , Interações Medicamentosas , Sucos de Frutas e Vegetais/análise , Pectinas/farmacologia , Proantocianidinas/farmacologia , Antioxidantes/química , Biflavonoides/química , Células CACO-2 , Catequina/química , Humanos , Pectinas/química , Proantocianidinas/química , Espectrometria de Fluorescência
19.
Food Funct ; 12(9): 3978-3991, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977989

RESUMO

Tyrosinase is considered a molecular marker of melanoma, and few natural antitumor drugs targeting tyrosinase have been identified. In this study, proanthocyanidins (PAs) were isolated from the leaves of Photinia × fraseri and their structures were characterized by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the effects of antityrosinase activity were investigated. The results showed that the basic structural units of PAs are composed of catechin and epicatechin and that oligomer is the main component. PAs exhibited better antityrosinase activity via chelation of copper ions and by disturbing o-quinone production. Furthermore, analyses of the cell cycle, apoptosis rate, and regulation of melanin protein expression revealed preliminarily that PAs could affect melanin production by downregulating microphthalmia transcription factor (MITF) expression and by inhibiting the activities of tyrosinase and tyrosinase related protein 1 (TRP-1), leading to cell cycle arrest and apoptosis of melanoma cells. Collectively, our study demonstrated that PAs are potential tyrosinase inhibitors and have good antimelanoma effects. These findings provide a theoretical support for the application of tyrosinase inhibitors and for further drug development.


Assuntos
Apoptose , Ciclo Celular/efeitos dos fármacos , Melanoma Experimental/patologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Photinia/química , Proantocianidinas/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Levodopa/química , Levodopa/metabolismo , Melaninas/biossíntese , Melaninas/genética , Melanoma Experimental/enzimologia , Melanoma Experimental/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Oxirredução , Oxirredutases/genética , Oxirredutases/metabolismo , Ácido Periódico , Folhas de Planta/química , Proantocianidinas/química , Proantocianidinas/isolamento & purificação
20.
Food Funct ; 12(12): 5375-5386, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33982735

RESUMO

Animal studies and clinical trials have shown that dietary polyphenols and polyphenol-rich foods can reduce the risk of type 2 diabetes (T2D) and its complications, but how diabetes regulates the metabolism of polyphenol has not been fully elucidated. This study investigated the effects of diabetes on litchi pericarp oligomeric procyanidin (LPOPC) dynamic metabolism and its major static metabolites in urine. First, a high-fat and streptozotocin (STZ)-induced diabetic Sprague Dawley (SD) rat model was established. In the diabetic rat model, elevated fasting blood glucose, severely impaired glucose tolerance test, and increased reactive oxygen species (ROS) levels in serum and the liver were observed. Subsequently, 200 mg per kg body weight of LPOPC was administrated to control and diabetic SD rats, and the gastrointestinal tract was collected at 0.5 h, 1 h, 3 h, and 6 h. The results showed that the retention time of LPOPC was not changed in our diabetic rat model. However, the gut microbiota were significantly altered, with elevated Proteobacteria and Verrucomicrobia abundance in diabetic rats and decreased short chain fatty acid (SCFA)-producing bacteria. Interestingly, after one dose of 300 mg per kg body weight LPOPC, the total antioxidant capacity of urine in diabetic rats significantly decreased. We then tested the static metabolites of LPOPC, demonstrating that epicatechin had not changed in urine in diabetic rats, but that shikimic acid was significantly reduced in urine in diabetic rats. The changes in shikimic acid may be due to the alteration of gut microbiota and elevated ROS levels in serum.


Assuntos
Biflavonoides/farmacologia , Catequina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Litchi/metabolismo , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum , Frutas/química , Masculino , RNA Ribossômico 16S , Ratos , Ratos Sprague-Dawley
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