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1.
Nutrients ; 14(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35268069

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF. AIM: The potential "therapeutic" effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-ß/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. DESIGN/METHODS: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg/kg body wt/day), carotene (10 mg/kg body wt/day), or a combination of TRF (200 mg/kg body wt/day) and carotene (10 mg/kg body wt/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues. RESULTS: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-ß1/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg/kg body wt/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats. CONCLUSION: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.


Assuntos
COVID-19 , Fibrose Pulmonar , Tocotrienóis , Animais , Bleomicina/toxicidade , Carotenoides/efeitos adversos , Humanos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Ratos , Ratos Sprague-Dawley , SARS-CoV-2 , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Tocotrienóis/efeitos adversos , Fator de Crescimento Transformador beta/metabolismo
2.
J Ethnopharmacol ; 281: 114511, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34390797

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the complications vexes patients treated with anti-cancer agents. Saffron has been demonstrated to attenuate symptoms of peripheral neuropathy in animal models. Also, there is a published clinical trial that investigated the pain relieving effect of saffron following nationally accepted rules and concluded that saffron was successful in alleviating pain symptoms in patients suffering from fibromyalgia. AIM OF THE STUDY: We aimed to determine the efficacy of crocin as a constituent of saffron in CIPN as the first report. MATERIALS AND METHODS: One hundred and seventy-seven enrolled eligible patients (between December 2018 and March 2020) for study entry were cases demonstrating mild to severe symptomatic CIPN for at least a month. These cases were randomly assigned to two main groups including 15 mg crocin tablet, bid (30 mg total daily target dose) and placebo tablet for 8 weeks. A crossover study was performed with a 2-week washout period. Patient outcomes were measured once a week for 8 consecutive weeks. RESULTS: Grade of sensory, motor and neuropathic pain decreased considerably and significantly in the crocin group compared with placebo (P < 0.05). Observed toxicities were mild and adverse effects had no significant differences between the two groups (P > 0.05). CONCLUSIONS: Crocin considerably seems to be effective for relieving symptoms of CIPN in cancer patients receiving chemotherapy agents. However, further studies are needed about crocin with its beneficial neuropharmacological effects and lower adverse effects than the chemical agents such as antidepressants, lamotrigine, and gabapentin.


Assuntos
Analgésicos/uso terapêutico , Antineoplásicos/efeitos adversos , Carotenoides/uso terapêutico , Crocus , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Carotenoides/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Resultado do Tratamento
3.
Drug Chem Toxicol ; 43(5): 514-521, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30714419

RESUMO

Ulcerative colitis is a chronic inflammatory bowel disease with high incidence and prevalence worldwide. To investigate the therapeutic potency of crocin, as a pharmacologically active component of saffron, in dextran sodium sulfate (DSS)-induced colitis mice model. Experimental colitis was induced by 7-day administration of DSS dissolved in water at a concentration of 1.5% (w/v). The animals were randomly divided into four groups (n»6 for each group). (1) Control group received regular drinking water for four weeks, (2) the second group of mice received regular drinking water for three weeks and then received DSS for one week, (3) and (4) the other two groups received 50-ppm or 200-ppm crocin for three weeks, respectively, and then treated with DSS for one week. Our results showed that Crocin attenuates colitis disease activity index including body weight loss, diarrhea, rectal bleeding, and colon shortening in crocin pre-tread mice. Comparison of histology of colon tissues between groups showed that crocin significantly decreases colon histopathological score, at least partially, by eliciting anti-inflammatory responses in DSS-induced colitis mice. These results clearly showed that crocin is a novel therapeutic agent with low toxicity as well as great clinical significance in treatment of colitis.


Assuntos
Carotenoides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Animais , Carotenoides/efeitos adversos , Carotenoides/farmacologia , Colite Ulcerativa/induzido quimicamente , Colo/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Molecules ; 24(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075966

RESUMO

Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.


Assuntos
Envelhecimento/fisiologia , Carotenoides/uso terapêutico , Doença , Disponibilidade Biológica , Carotenoides/efeitos adversos , Carotenoides/química , Carotenoides/metabolismo , Dieta , Humanos , Estresse Oxidativo
6.
Am J Ophthalmol ; 190: 89-98, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29550187

RESUMO

OBJECTIVE: Diabetic macular edema (DME) is one of the most important sight-threatening complications in patients with diabetes. Owing to neuroprotective properties, crocin, as the main constituent in saffron, is thought to be useful in the treatment and prevention of diabetic maculopathy. The aim of this trial was to evaluate the effects of crocin as a supplement on reducing inflammation in patients with diabetic maculopathy. DESIGN: Double-masked, placebo controlled, phase 2 randomized clinical trial. METHODS: Participants: In this study, 101 eyes of 60 patients with refractory diabetic maculopathy to conventional therapy including macular photocoagulation and intravitreal injection of anti-vascular endothelial growth factor agent (bevacizumab) with or without steroid (triamcinolone) were studied in 3 groups. INTERVENTION: Patients in the crocin groups received 5 mg or 15 mg crocin tablets per day for 3 months, whereas patients in the placebo group received 1 placebo tablet per day during the study. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured before, every month during, and 3 months after intervention. Biochemical blood tests were also evaluated before and after trial. MAIN OUTCOME MEASURES: The BCVA and CMT were evaluated as the primary outcomes, whereas HbA1c and fasting blood sugar (FBS) were studied as the secondary outcomes in this trial. RESULTS: One hundred and one eyes were enrolled in this trial and were divided into 3 groups (crocin 5 mg, n = 34; crocin 15 mg, n = 33; and placebo, n = 34). According to our data, administration of crocin 15 mg tablet per day could significantly decrease HbA1c (P value = .024; 95% confidence interval [CI] 0.3-0.96), and CMT (P value = .005; 95% CI, 32.75-126.99) and improve BCVA (logMAR changes; P value = .012; 95% CI, 0.23-0.69) compared to the placebo group. Although administration of crocin 5 mg tablet per day could clinically improve HbA1c, FBS, CMT, and BCVA, the difference was not significant compared to the placebo group. CONCLUSION: This study indicated the effect of crocin as a potent antioxidant and neuroprotective for treatment of refractory DME in the short term; however, the clinical significance is yet to be proved in a study with larger sample size and longer duration of follow-up and also in treatment-naïve patients.


Assuntos
Carotenoides/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Carotenoides/efeitos adversos , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Testes de Função Hepática , Macula Lutea/patologia , Edema Macular/diagnóstico por imagem , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placebos , Comprimidos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
7.
J Pharm Pharmacol ; 69(11): 1419-1427, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28675431

RESUMO

OBJECTIVES: Crocin is derived from dried stigmas of Crocus sativus L. (saffron). It has long been used to prevent and treat various diseases. Although crocin is suggested as one of the most effective cancer therapeutic constituents of saffron stigma, its exact molecular mechanisms are not fully understood. In this study, we reviewed anticancer effects of crocin and its underlying molecular mechanisms. KEY FINDINGS: While several mechanisms may account for the antitumour activity of crocin, alteration of expression/activity of the genes and also epigenetic changes may be considered as necessary phenomena. These alternations may lead to inhibition of cancer cells' proliferation or/and induction of apoptosis through various mechanism including inhibition of synthesis of DNA and RNA, interaction with cellular topoisomerase, suppression of the telomerase activity and active STAT3, and targeting of microtubules. Moreover, this carotenoid could reverse the epithelial-mesenchymal transition and inhibit metastasis. CONCLUSIONS: Knowing molecular mechanisms of antitumoral agents could guide us to choose the best chemotherapeutic compound especially for targeted therapy and also provide insights about possible side effects.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carotenoides/farmacologia , Crocus/química , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carotenoides/efeitos adversos , Carotenoides/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia
8.
Biomed Pharmacother ; 92: 86-94, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28531804

RESUMO

Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear. To investigate the effect of Lyc on EPCs, we isolated EPCs from DM rat bone marrow and determined cell proliferation, cell cycle,apoptosis and autophagy of EPCs. The present study showed that 10µg/mL Lyc improved cell proliferation and had low cytotoxicity in the presence of AGEs. In addition, Lyc rescued S phase of the cell cycle arrest, reduced apoptosis rate and decreased autophagic reaction including ROS and mitochondrial membrane potential (MMP) of EPCs. Moreover, Lyc combined use of autophagy inhibitors, 3-MA, had better protective effects. Taken together, our data suggests that Lyc promotes EPCs survival and protect EPCs from apoptosis and oxidative autophagy induced by AGEs, further remaining the number and function of EPCs. This study provides new insights into Lyc protective mechanism of AGEs-induced oxidative autophagy in EPCs from DM patients and offers a new therapy for DM vascular complications.


Assuntos
Antioxidantes/metabolismo , Autofagia , Carotenoides/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Estresse Oxidativo , Animais , Antioxidantes/efeitos adversos , Apoptose , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células da Medula Óssea/ultraestrutura , Carotenoides/efeitos adversos , Proliferação de Células , Células Cultivadas , Diabetes Mellitus Tipo 2/patologia , Suplementos Nutricionais/efeitos adversos , Células Progenitoras Endoteliais/patologia , Células Progenitoras Endoteliais/ultraestrutura , Produtos Finais de Glicação Avançada/efeitos adversos , Licopeno , Potencial da Membrana Mitocondrial , Microscopia Eletrônica de Transmissão , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Fase S
9.
Food Chem Toxicol ; 103: 233-245, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28202360

RESUMO

4-nitroquinoline-1-oxide (4-NQO) is a pro-oxidant carcinogen bioactivated by xenobiotic metabolism (XM). We investigated if antioxidants lycopene [0.45, 0.9, 1.8 µM], resveratrol [11, 43, 172 µM], and vitamin C [5.6 mM] added or not with FeSO4 [0.06 mM], modulate the genotoxicity of 4-NQO [2 mM] with the Drosophila wing spot test standard (ST) and high bioactivation (HB) crosses, with inducible and high levels of cytochromes P450, respectively. The genotoxicity of 4-NQO was higher when dissolved in an ethanol - acetone mixture. The antioxidants did not protect against 4-NQO in any of both crosses. In the ST cross, resveratrol [11 µM], vitamin C and FeSO4 resulted in genotoxicity; the three antioxidants and FeSO4 increased the damage of 4-NQO. In the HB cross, none of the antioxidants, neither FeSO4, were genotoxic. Only resveratrol [172 µM] + 4-NQO increased the genotoxic activity in both crosses. We concluded that the effects of the antioxidants, FeSO4 and the modulation of 4-NQO were the result of the difference of Cyp450s levels, between the ST and HB crosses. We propose that the basal levels of the XM's enzymes in the ST cross interacted with a putative pro-oxidant activity of the compounds added to the pro-oxidant effects of 4-NQO.


Assuntos
4-Nitroquinolina-1-Óxido/toxicidade , Ácido Ascórbico/farmacologia , Carotenoides/farmacologia , Compostos Ferrosos/farmacologia , Estilbenos/farmacologia , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/efeitos adversos , Carcinógenos/toxicidade , Carotenoides/efeitos adversos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Feminino , Compostos Ferrosos/efeitos adversos , Larva/efeitos dos fármacos , Licopeno , Masculino , Resveratrol , Estilbenos/efeitos adversos , Testes de Toxicidade/métodos , Asas de Animais/efeitos dos fármacos , Xenobióticos/toxicidade
10.
J Sci Food Agric ; 97(3): 1027-1033, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27256857

RESUMO

BACKGROUND: Z-isomers of lycopene, which are abundantly present in processed tomato products, are more bioavailable than (all-E)-lycopene found predominantly in raw tomatoes. Despite extensive studies on the bioavailability and biological activities of Z-isomers of lycopene, detailed studies on their safety and toxicology are limited. RESULTS: The geno-, acute and subacute toxicities of tomato oleoresin that contained high amounts of lycopene Z-isomers (10.9% lycopene with 66.3% Z-isomer content) and had been prepared with supercritical carbon dioxide were investigated. The oleoresin was non-mutagenic in the Ames test with and without metabolic activation (S9 mix). The medial lethal dose (LD50 ) of the oleoresin in rats, as determined by a single-dose oral test, was more than 5000 mg kg body weight-1 (bw) [361 mg (Z)-lycopene kg bw-1 ]. In the 4-week repeated-dose oral toxicity test, rats were administered oleoresin at 4500 mg kg-1 day-1 [325 mg (Z)-lycopene kg bw-1 day-1 ]. There were no clinically significant changes with respect to vital signs, physical examination outcomes and laboratory test values during the test period. CONCLUSION: Based on our findings and as supported by its long history of consumption, tomato oleoresin that contains high amounts of Z-isomers of lycopene prepared with supercritical carbon dioxide can be considered as safe for human consumption. © 2016 Society of Chemical Industry.


Assuntos
Carotenoides/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Aditivos Alimentares/efeitos adversos , Frutas/química , Extratos Vegetais/efeitos adversos , Solanum lycopersicum/química , Animais , Dióxido de Carbono/química , Carotenoides/química , Carotenoides/isolamento & purificação , Carotenoides/metabolismo , Cromatografia com Fluido Supercrítico , Feminino , Aditivos Alimentares/química , Aditivos Alimentares/isolamento & purificação , Aditivos Alimentares/metabolismo , Manipulação de Alimentos , Dose Letal Mediana , Licopeno , Masculino , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Testes de Mutagenicidade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Ratos , Ratos Wistar , Estereoisomerismo , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
11.
Eur J Cancer Prev ; 26(1): 27-37, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26960163

RESUMO

Carotenoid intake from natural sources has been hypothesized to reduce the risk of colorectal cancer (CRC). The aim of this study was to systematically review the epidemiological evidence for the association between carotenoid intake from natural sources and CRC development. We carried out a systematic review and meta-analysis of epidemiological studies to investigate whether the intake of specific carotenoids from natural sources, as well as combined carotenoids, is associated with the risk of CRC overall and by anatomic subsite. A comprehensive literature search of MEDLINE and Scopus databases was performed. Twenty-two articles were identified from the literature search, of which 16 were case-control studies and 6 were cohort studies. In the random-effects meta-analysis of case-control and cohort studies, we found no association between the intake of individual and total carotenoids and the risk of CRC overall and by anatomic subsite. Overall, our findings do not support a significant association between intake of specific carotenoids from dietary sources, as well as combined carotenoids, and the risk of CRC overall and by anatomic subsite.


Assuntos
Carotenoides/administração & dosagem , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Carotenoides/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/induzido quimicamente , Dieta/efeitos adversos , Humanos , Fatores de Risco , Verduras/efeitos adversos
12.
Toxicol Lett ; 236(3): 154-67, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-25980574

RESUMO

A trend in the general population has been observed in recent years regarding the orientation toward preventive measures in health; in this context the increased interest from the users and researchers concerning the active effect of food supplements on the health state and on longevity, is noticeable. All over the world, the consumption of natural foods and of vegetal supplements has increased spectacularly over the last 5-10 years. The decreased prevalence of cardio-vascular diseases associated with Mediterranean diet, as well as the French paradox convinced researchers to scientifically document the beneficial outcomes pointed out by traditional use of plants, and to try to develop supplements that would have the same positive effects as these noticed for diet components. The intense research dedicated to this topic revealed the fact that food supplements are linked to some problematic aspects, such as toxicological side effects when associated with classical synthetic drugs. The food supplement-drug interactions are submitted to complex issues regarding pharmacokinetic interactions leading to changes in absorption, distribution, metabolism and excretion processes with direct impact on effect and toxicological potential. The present review based on recent literature aims at discussing the food-drug interactions with direct impact on efficacy and toxicity of drugs.


Assuntos
Produtos Biológicos/efeitos adversos , Produtos Biológicos/farmacologia , Carotenoides/efeitos adversos , Carotenoides/farmacologia , Citrus paradisi , Curcumina/efeitos adversos , Curcumina/análogos & derivados , Curcumina/farmacologia , Humanos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Polifenóis/efeitos adversos , Polifenóis/farmacologia
13.
J Nutr Biochem ; 26(7): 736-44, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25869595

RESUMO

BACKGROUND: Neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). ß-Amyloid1-42 (Aß1-42)-induced learning and memory impairment in rats is believed to be associated with neuronal inflammation. OBJECTIVES: The present study was designed to investigate the effect of lycopene, a potent antioxidant and anti-inflammatory carotenoid, in intracerebroventricular (i.c.v.) Aß1-42-induced neuroinflammatory cascade along with learning and memory impairment in rats. MATERIAL AND METHODS: I.c.v. Aß1-42 was injected bilaterally followed by treatment with lycopene or rivastigmine for 14 days. Morris water maze and elevated plus maze tests were used to assess the memory function. Rats were sacrificed and brains harvested to evaluate various biochemical parameters and mitochondrial complex activities in postmitochondrial supernatant fractions of cerebral cortex and hippocampus of rat brains. The levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), tumor growth factor ß (TGF-ß), nuclear factor-κB (NF-κB) and caspase-3 were assessed by enzyme-linked immunosorbent assay analysis. RESULTS: Lycopene remediated Aß-induced learning and memory deficits in a dose-dependent manner. Aß1-42-induced mitochondrial dysfunction along with surge of proinflammatory cytokines TNF-α, TGF-ß and IL-1ß as well as NF-κB and caspase-3 activity in rat brain was significantly reduced with lycopene treatment. CONCLUSION: The amelioration of Aß1-42-induced spatial learning and memory impairment by lycopene could be linked, at least in part, to the inhibition of NF-κB activity and the down-regulation of expression of neuroinflammatory cytokines, suggesting that lycopene may be a potential candidate for AD treatment.


Assuntos
Doença de Alzheimer/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico , Carotenoides/uso terapêutico , Suplementos Nutricionais , Modelos Animais de Doenças , Neurônios/metabolismo , Nootrópicos/uso terapêutico , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Antioxidantes/uso terapêutico , Comportamento Animal , Carotenoides/administração & dosagem , Carotenoides/efeitos adversos , Caspase 3/química , Caspase 3/metabolismo , Córtex Cerebral/imunologia , Córtex Cerebral/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Suplementos Nutricionais/efeitos adversos , Comportamento Exploratório , Hipocampo/imunologia , Hipocampo/metabolismo , Licopeno , Masculino , Aprendizagem em Labirinto , Consolidação da Memória , Neurônios/imunologia , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/uso terapêutico , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Fragmentos de Peptídeos , Distribuição Aleatória , Ratos Wistar
14.
Food Chem Toxicol ; 59: 78-85, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23669408

RESUMO

Astaxanthin, ß-cryptoxanthin, canthaxanthin, lutein and zeaxanthin, the major xanthophylls, are widely used in food, medicine, and health care products. To date, no studies regarding the inhibitory effects of these xanthophylls on the nine CYPs isozymes have been reported. This study investigated the reversible and time-dependent inhibitory potentials of five xanthophylls on CYPs activities in vitro. The reversible inhibition results showed that the five compounds had only a weak inhibitory effect on the nine CYPs. Lutein did not inhibit the nine CYPs activities. Astaxanthin weakly inhibited CYP2C19, with an IC50 of 16.2 µM; and ß-cryptoxanthin weakly inhibited CYP2C8, with an IC50 of 13.8 µM. In addition, canthaxanthin weakly inhibited CYP2C19 and CYP3A4/5, with IC50 values of 10.9 and 13.9 µM, respectively. Zeaxanthin weakly inhibited CYP3A4/5, with an IC50 of 15.5 µM. However, these IC50 values were markedly greater than the Cmax values reported in humans. No significant IC50 shift was observed in the time-dependent inhibition screening. Based on these observations, it is unlikely that these five xanthophylls from the diet or nutritional supplements alter the pharmacokinetics of drugs metabolized by CYPs. These findings provide some useful information for the safe use of these five xanthophylls in clinical practice.


Assuntos
Carotenoides/metabolismo , Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/metabolismo , Microssomos Hepáticos/metabolismo , Xenobióticos/metabolismo , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Hidrocarboneto de Aril Hidroxilases/metabolismo , Biotransformação , Cantaxantina/efeitos adversos , Cantaxantina/metabolismo , Carotenoides/efeitos adversos , Criptoxantinas , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Suplementos Nutricionais/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Interações Alimento-Droga , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Cinética , Luteína/efeitos adversos , Luteína/metabolismo , Microssomos Hepáticos/enzimologia , Xantofilas/efeitos adversos , Xantofilas/metabolismo , Zeaxantinas
15.
Crit Rev Food Sci Nutr ; 53(2): 198-213, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23072533

RESUMO

In recent years, both food quality and its effect on human health have become a fundamental issue all over the world. As a consequence of this new and increased awareness, American, European, and Asian policymakers have strongly encouraged the research programs on food quality and safety thematic. Attempts to improve human health and to satisfy people's desire for healthcare without intake of pharmaceuticals, has led the food industry to focus attention on functional or nutraceutical food. For a long time, compounds with nutraceutical activity have been produced chemically, but the new demands for a sustainable life have gradually led the food industry to move towards natural compounds, mainly those derived from plants. Many phytochemicals are known to promote good health, but, sometimes, undesirable effects are also reported. Furthermore, several products present on the market show few benefits and sometimes even the reverse - unhealthy effects; the evidence of efficacy is often unconvincing and epidemiological studies are necessary to prove the truth of their claims. Therefore, there is a need for reliable analytical control systems to measure the bioactivity, content, and quality of these additives in the complex food matrix. This review describes the most widespread nutraceutics and an analytical control of the same using recently developed biosensors which are promising candidates for routine control of functional foods.


Assuntos
Suplementos Nutricionais/efeitos adversos , Suplementos Nutricionais/análise , Plantas Comestíveis/química , Animais , Capsaicina/efeitos adversos , Carotenoides/efeitos adversos , Cisteína/efeitos adversos , Cisteína/análogos & derivados , Gorduras Insaturadas na Dieta , Dissulfetos , Ácidos Graxos Insaturados/efeitos adversos , Alimento Funcional/análise , Glucosinolatos/efeitos adversos , Humanos , Política Nutricional , Fenóis/efeitos adversos , Fitoestrógenos/efeitos adversos , Polifenóis/administração & dosagem , Polifenóis/efeitos adversos , Ácidos Sulfínicos/efeitos adversos
16.
Am J Clin Nutr ; 96(3): 534-43, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22854412

RESUMO

BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.


Assuntos
Antioxidantes/uso terapêutico , Asma/dietoterapia , Frutas , Estresse Oxidativo , Verduras , Adulto , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Asma/sangue , Asma/imunologia , Asma/fisiopatologia , Proteína C-Reativa/análise , Carotenoides/efeitos adversos , Carotenoides/análise , Carotenoides/uso terapêutico , Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Frutas/efeitos adversos , Frutas/química , Humanos , Mediadores da Inflamação/sangue , Licopeno , Solanum lycopersicum/efeitos adversos , Solanum lycopersicum/química , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Sistema Respiratório/fisiopatologia , Verduras/efeitos adversos , Verduras/química
17.
Curr Pharm Biotechnol ; 13(1): 180-90, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21466428

RESUMO

Recently nontoxic natural compounds are getting immense importance for the prevention of diseases of different etiology. Natural product provitamin A "carotenoids", largely α-carotene, ß-carotene, and ß-cryptoxanthin, are typical constituents of orange/red/yellow colored fruits and green vegetables. Different in vitro and in vivo studies have shown that carotenoids possess the capacity to scavenge DNA damaging free radicals, suppress angiogenesis, inhibit cell proliferation and induce apoptosis. Epidemiological reports of case-control studies, nested case-control studies, and cohort studies support significant association between dietary intake and circulating levels of carotenoids and reduction in cancer risk/carcinoma of various organs. However, randomized trials regarding ß-carotene supplementation, alone or in combination with other supplements, have not always well corroborated with this. Of seven trials, one observed a significant benefit on cancer mortality, four reported no significant benefit or harm, while the remaining two trials found an unexpected, but significant increase in lung cancer incidence. This review discusses implications and significance of carotenoids in the field of cancer risk and prevention.


Assuntos
Anticarcinógenos/uso terapêutico , Carotenoides/uso terapêutico , Neoplasias/prevenção & controle , Animais , Anticarcinógenos/efeitos adversos , Carotenoides/efeitos adversos , Humanos , Neoplasias/epidemiologia , Neoplasias/etiologia , Risco
18.
Urol Int ; 84(4): 400-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20332612

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of Serenoa repens + selenium and lycopene (Profluss) versus S. repens alone for the treatment of category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: 102 patients with IIIa CP/CPPS were enrolled and randomized into two groups each to receive Profluss or S. repens alone for 8 weeks. Evaluation was based on results of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), IPSS, maximum peak flow rate (MPFR), and PSA measurements at baseline and at weeks 4, 8 and 8 after the end of treatment. The primary endpoint was a >50% reduction in NIH-CPSI score. Secondary endpoints evaluated were MPFR, IPSS, PSA and white blood cell count. RESULTS: No patients withdrew from the study. The mean NIH-CPSI score decreased significantly (p < 0.001) in both groups; we observed a decrease in the total score from 27.45 to 13.27 in group 1 (-51.64%) and from 27.76 to 20.62 in group 2 (-26.06%). IPSS improved significantly (p < 0.001) in both arms, but more in group 1. PSA and white blood cell count decreased significantly (p < 0.007) only in group 1. The MPFR improved more in group 1 (p < 0.005). CONCLUSION: Profluss is a triple therapy that is safe and well tolerated. It ameliorates symptoms associated with IIIa CP/CPPS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Carotenoides/uso terapêutico , Dor Pélvica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Prostatite/tratamento farmacológico , Selênio/uso terapêutico , Serenoa , Adulto , Anti-Inflamatórios/efeitos adversos , Carotenoides/efeitos adversos , Doença Crônica , Método Duplo-Cego , Combinação de Medicamentos , Humanos , Itália , Contagem de Leucócitos , Licopeno , Masculino , Pessoa de Meia-Idade , Dor Pélvica/sangue , Dor Pélvica/fisiopatologia , Dor Pélvica/urina , Extratos Vegetais/efeitos adversos , Antígeno Prostático Específico/sangue , Prostatite/sangue , Prostatite/fisiopatologia , Prostatite/urina , Selênio/efeitos adversos , Índice de Gravidade de Doença , Síndrome , Fatores de Tempo , Resultado do Tratamento , Urina/citologia , Urodinâmica , Adulto Jovem
20.
Curr Opin Clin Nutr Metab Care ; 13(1): 28-33, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19841580

RESUMO

PURPOSE OF REVIEW: The purpose of the present review is to evaluate the most recent evidence for a role of antioxidant nutrients in the prevention or delay in progression of age-related macular degeneration (AMD), a major cause of visual impairment and blindness in the aging population. RECENT FINDINGS: Recent human studies (>2008) report a decreased AMD risk with increased intakes of lutein/zeaxanthin, B vitamins, zinc and docosahexaenoic acid but an increased risk with increased intakes of beta-carotene and vitamin E. These latter findings are inconsistent with previous reports (<2008). SUMMARY: Findings on the association of certain antioxidants and docosahexaenoic acid support a role for nutrition in a decreased risk of AMD. The inconsistent findings of an increased risk with increased intake of beta-carotene and vitamin E warrants continued investigation into these relationships.


Assuntos
Antioxidantes/uso terapêutico , Degeneração Macular/prevenção & controle , Micronutrientes/uso terapêutico , Carotenoides/efeitos adversos , Carotenoides/uso terapêutico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Humanos , Fatores de Risco , Vitamina E/efeitos adversos , Vitamina E/uso terapêutico
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