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1.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443567

RESUMO

Redox-active iron generates reactive oxygen species that can cause oxidative organ dysfunction. Thus, the anti-oxidative systems in the body and certain dietary antioxidants, such as anthocyanins, are needed to control oxidative stress. We aimed to investigate the effects of dielectric barrier discharge (DBD) plasma technology in the preparation of Riceberry™ rice flour (PRBF) on iron-induced oxidative stress in mice. PRBF using plasma technology was rich in anthocyanins, mainly cyanidine-3-glucoside and peonidine-3-glucoside. PRBF (5 mg AE/mg) lowered WBC numbers in iron dextran (FeDex)-loaded mice and served as evidence of the reversal of erythrocyte superoxide dismutase activity, plasma total antioxidant capacity, and plasma and liver thiobarbituric acid-reactive substances in the loading mice. Consequently, the PRBF treatment was observed to be more effective than NAC treatment. PRBF would be a powerful supplementary and therapeutic antioxidant product that is understood to be more potent than NAC in ameliorating the effects of iron-induced oxidative stress.


Assuntos
Antocianinas/análise , Antioxidantes/farmacologia , Farinha/análise , Ferro/efeitos adversos , Oryza/química , Estresse Oxidativo/efeitos dos fármacos , Gases em Plasma/química , Animais , Impedância Elétrica , Camundongos
2.
Molecules ; 26(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34279413

RESUMO

Malaria i a serious health problem caused by Plasmodium spp. that can be treated by an anti-folate pyrimethamine (PYR) drug. Deferiprone (DFP) is an oral iron chelator used for the treatment of iron overload and has been recognized for its potential anti-malarial activity. Deferiprone-resveratrol hybrids (DFP-RVT) have been synthesized to present therapeutic efficacy at a level which is superior to DFP. We have focused on determining the lipophilicity, toxicity and inhibitory effects on P. falciparum growth and the iron-chelating activity of labile iron pools (LIPs) by DFP-RVT. According to our findings, DFP-RVT was more lipophilic than DFP (p < 0.05) and nontoxic to blood mononuclear cells. Potency for the inhibition of P. falciparum was PYR > DFP-RVT > DFP in the 3D7 strain (IC50 = 0.05, 16.82 and 47.67 µM, respectively) and DFP-RVT > DFP > PYR in the K1 strain (IC50 = 13.38, 42.02 and 105.61 µM, respectively). The combined treatment of DFP-RVT with PYR additionally enhanced the PYR activity in both strains. DFP-RVT dose-dependently lowered LIP levels in PRBCs and was observed to be more effective than DFP at equal concentrations. Thus, the DFP-RVT hybrid should be considered a candidate as an adjuvant anti-malarial drug through the deprivation of cellular iron.


Assuntos
Antimaláricos/farmacologia , Deferiprona/farmacologia , Eritrócitos/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Resveratrol/farmacologia , Antioxidantes/farmacologia , Eritrócitos/parasitologia , Humanos , Quelantes de Ferro/farmacologia , Malária Falciparum/parasitologia
3.
Molecules ; 26(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34299444

RESUMO

We aimed to analyze the chemical compositions in Arabica coffee bean extracts, assess the relevant antioxidant and iron-chelating activities in coffee extracts and instant coffee, and evaluate the toxicity in roasted coffee. Coffee beans were extracted using boiling, drip-filtered and espresso brewing methods. Certain phenolics were investigated including trigonelline, caffeic acid and their derivatives, gallic acid, epicatechin, chlorogenic acid (CGA) and their derivatives, p-coumaroylquinic acid, p-coumaroyl glucoside, the rutin and syringic acid that exist in green and roasted coffee extracts, along with dimethoxycinnamic acid, caffeoylarbutin and cymaroside that may be present in green coffee bean extracts. Different phytochemicals were also detected in all of the coffee extracts. Roasted coffee extracts and instant coffees exhibited free-radical scavenging properties in a dose-dependent manner, for which drip coffee was observed to be the most effective (p < 0.05). All coffee extracts, instant coffee varieties and CGA could effectively bind ferric ion in a concentration-dependent manner resulting in an iron-bound complex. Roasted coffee extracts were neither toxic to normal mononuclear cells nor breast cancer cells. The findings indicate that phenolics, particularly CGA, could effectively contribute to the iron-chelating and free-radical scavenging properties observed in coffee brews. Thus, coffee may possess high pharmacological value and could be utilized as a health beverage.


Assuntos
Coffea/química , Sequestradores de Radicais Livres/análise , Proteínas de Ligação ao Ferro/análise , Alcaloides , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Ácido Clorogênico/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Coffea/toxicidade , Café/química , Café/toxicidade , Temperatura Alta , Humanos , Ferro/análise , Espectrometria de Massas/métodos , Fenóis/farmacologia , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Extratos Vegetais/análise , Extratos Vegetais/química , Sementes/química
4.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33399183

RESUMO

Perilla frutescens fruit oil (PFO) is rich in α-linolenic acid (ALA) and exhibits biological activities. We aimed to investigate analgesic, anti-inflammatory and anti-ulcer activities of PFO and PFO-supplemented soybean milk (PFO-SM) in animal models. Analgesic activity was assessed in acetic acid-induced writhing in mice, while anti-inflammatory activity was performed in ethyl phenylpropiolate (EPP)-induced ear edema and carrageenan-induced hind paw edema in rats. Anti-ulcer effects were conducted in water immersion stress, HCl/ethanol and indomethacin-induced gastric ulcer in rats. Distinctly, PFO, containing 6.96 mg ALA and 2.61 mg LA equivalence/g, did not induce acute toxicity (LD50 > 10 mL/kg) in mice. PFO (2.5 and 5 mL/kg) and PFO-SM (0.05 mL PFO equivalence/kg) inhibited incidences of writhing (16.8, 18.0 and 32.3%, respectively) in acetic acid-induced mice. In addition, topical applications of PFO (0.1 and 1 mL/ear) significantly inhibited EPP-induced ear edema (59.3 and 65.7%, respectively) in rats, while PFO-SM slightly inhibited ear edema (25.9%). However, PFO and PFO-SM did not inhibit carrageenan-induced hind paw edema in rats. Indeed, PFO (2.5 and 5 mL/kg) significantly inhibited gastric ulcers in rats that induced by water immersion stress (92.4 and 96.6%, respectively), HCl/ethanol (74.8 and 73.3%, respectively) and indomethacin (68.8 and 88.9%, respectively), while PFO-SM did not. PFO displayed potent analgesic, anti-inflammatory and anti-ulcer properties, while PFO-SM exerted only analgesic properties. Thus, Thai PFO and its functional drink offer potential benefits in treatment of analgesic, inflammatory diseases and gastric ulcer.

5.
Food Funct ; 11(1): 932-943, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31950948

RESUMO

The most important cause of death in ß-thalassemia major patients is organ dysfunction due to iron deposits. Non-transferrin bound iron (NTBI), labile plasma iron (LPI) and labile iron pool are redox-active forms of iron found in thalassemia. Iron chelation therapy is adopted to counteract the resulting iron overload. Extracts of green tea (GTE) and curcumin exhibit iron-chelating and antioxidant activities in iron-loaded cells and ß-thalassemic mice. We have used our GTE-CUR drink to investigate the potential amelioration of iron overload and oxidative stress in transfusion-dependent ß-thalassemia (TDT) patients. The patients were enrolled for a control group without and with GTE-CUR treatments (17.3 and 35.5 mg EGCG equivalent). Along with regular chelation therapy, they were daily administered the drink for 60 d. Blood samples were collected at the beginning of the study and after 30 d and 60 d for biochemical and hematological tests. Interestingly, we found a decrease of blood urea nitrogen levels (P < 0.05), along with a tendency for a decrease of NTBI and LPI, and a delay in increasing lipid-peroxidation product levels in the GTE-CUR groups. The findings suggest that GTE-CUR could increase kidney function and diminish redox-active iron in iron overloaded ß-thalassemia patients.


Assuntos
Antioxidantes/uso terapêutico , Nitrogênio da Ureia Sanguínea , Curcumina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Chá , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Adulto Jovem
6.
Pancreas ; 48(5): 636-643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091209

RESUMO

OBJECTIVES: We have investigated the efficacy of mono- and combined therapy with green tea extract (GTE) in mobilizing redox iron, scavenging reactive oxygen species (ROS), and improving insulin production in iron-loaded pancreatic cells. METHODS: Rat insulinoma pancreatic ß-cells were iron-loaded using culture medium supplemented with either fetal bovine serum or ferric ammonium citrate and treated with various doses of GTE for epigallocatechin-3-gallate (EGCG) equivalence and in combination with iron chelators. Cellular iron, ROS, and secretory insulin were measured. RESULTS: The rat insulinoma pancreatic cells took up iron from fetal bovine serum more rapidly than ferric ammonium citrate. After treatment with GTE (0.23-2.29 µg EGCG equivalent), cellular levels of iron and ROS were dose dependently decreased. Importantly, secretory insulin levels were increased nearly 2.5-fold with 2.29 µg of EGCG equivalent GTE, indicating a recovery in insulin production. CONCLUSIONS: Green tea EGCG ameliorated oxidative damage of iron-loaded ß-cells by removing redox iron and free radicals and attenuating insulin production. The impact can result in the restoration of pancreatic functions and an increase in insulin production. Green tea extract exerts iron-chelating, free-radical scavenging, and pancreato-protective effects in the restoration of ß-cell functions, all of which we believe can increase insulin production in diabetic ß-thalassemia patients.


Assuntos
Catequina/análogos & derivados , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ferro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Chá/química , Animais , Catequina/farmacologia , Linhagem Celular Tumoral , Complicações do Diabetes/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Ratos , Talassemia beta/complicações , Talassemia beta/metabolismo
7.
Biomed Pharmacother ; 108: 1694-1702, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372872

RESUMO

Iron overload in patients with ß-thalassemia can cause oxidative organ dysfunction. Iron chelation along with antioxidant supplementation can ameliorate such complications and prolong lives. Green tea extract (GTE) rich in epigallocatechin-3-gallate (EGCG) exhibits anti-oxidation and iron chelation properties in ß-knockout thalassemic (BKO) mice diagnosed with iron overload. We investigated the effects of GTE and deferiprone (DFP) alone in combination with one another, and upon the levels of redox-active iron, lipid-peroxidation product, insulin and hepcidin in BKO mice. A state of iron overload was induced in the mice via a trimethylhexanoyl-ferrocene supplemented (Fe) diet for 3 months, and the mice were treated daily with either: DFP (50 mg/kg), DFP (50 mg/kg) plus GTE (50 mg EGCG equivalent/kg), or GTE alone for 2 months. Plasma non-transferrin bound iron (NTBI), malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepcidin and insulin; tissue iron and MDA were measured. DFP, GTE and GTE + DFP effectively decreased plasma MDA (p < 0.05), NTBI and ALT, and increased plasma hepcidin and insulin. All the treatments also reduced iron accumulation and MDA production in both the pancreas and liver in the mice. However, the combination therapy demonstrated no advantages over monotherapy. The findings suggest GTE improved liver and pancreatic ß-cell functions in iron-overloaded ß-thalassemia mice by diminishing redox iron and free radicals, while inhibiting lipid peroxidation. Consequently, there are indications that GTE holds significant potential for clinical use.


Assuntos
Catequina/análogos & derivados , Quelantes de Ferro/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Chá/química , Talassemia beta/patologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Catequina/farmacologia , Hematopoese/efeitos dos fármacos , Hepcidinas/sangue , Insulina/sangue , Ferro/sangue , Ferro/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Talassemia beta/sangue
8.
Blood ; 130(17): 1923-1933, 2017 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-28864815

RESUMO

Eltrombopag (ELT) is a thrombopoietin receptor agonist reported to decrease labile iron in leukemia cells. Here we examine the previously undescribed iron(III)-coordinating and cellular iron-mobilizing properties of ELT. We find a high binding constant for iron(III) (log ß2=35). Clinically achievable concentrations (1 µM) progressively mobilized cellular iron from hepatocyte, cardiomyocyte, and pancreatic cell lines, rapidly decreasing intracellular reactive oxygen species (ROS) and also restoring insulin secretion in pancreatic cells. Decrements in cellular ferritin paralleled total cellular iron removal, particularly in hepatocytes. Iron mobilization from cardiomyocytes exceeded that obtained with deferiprone, desferrioxamine, or deferasirox at similar iron-binding equivalents. When combined with these chelators, ELT enhanced cellular iron mobilization more than additive (synergistic) with deferasirox. Iron-binding speciation plots are consistent with ELT donating iron to deferasirox at clinically relevant concentrations. ELT scavenges iron citrate species faster than deferasirox, but rapidly donates the chelated iron to deferasirox, consistent with a shuttling mechanism. Shuttling is also suggested by enhanced cellular iron mobilization by ELT when combined with the otherwise ineffective extracellular hydroxypyridinone chelator, CP40. We conclude that ELT is a powerful iron chelator that decreases cellular iron and further enhances iron mobilization when combined with clinically available chelators.


Assuntos
Benzoatos/farmacologia , Espaço Extracelular/metabolismo , Hidrazinas/farmacologia , Quelantes de Ferro/farmacologia , Ferro/metabolismo , Pirazóis/farmacologia , Animais , Benzoatos/química , Linhagem Celular Tumoral , Desferroxamina/farmacologia , Ferritinas/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hidrazinas/química , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Pirazóis/química , Piridonas/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
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