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1.
Life Sci ; 256: 118016, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603817

RESUMO

AIMS: Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway. MAIN METHODS: The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 µg/kg, i.p.). KEY FINDINGS: The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-α, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury. SIGNIFICANCE: The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.


Assuntos
Lesão Renal Aguda/prevenção & controle , Curcumina/farmacologia , Inflamação/prevenção & controle , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Curcumina/administração & dosagem , Inibidores de Lipoxigenase/administração & dosagem , Inibidores de Lipoxigenase/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Semaforina-3A/sangue , Semaforinas/metabolismo
2.
Life Sci ; 256: 118003, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589998

RESUMO

INTRODUCTION AND AIMS: Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies. METHODS: PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days. FINDINGS: PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased ß cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels. SIGNIFICANCE: To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.


Assuntos
Curcumina/farmacologia , Resistência à Insulina , Nanopartículas , Pâncreas/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Curcumina/administração & dosagem , Modelos Animais de Doenças , Feminino , Pâncreas/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Life Sci ; 256: 117984, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593707

RESUMO

Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Curcumina/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linhagem Celular Tumoral , Curcumina/efeitos adversos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Paclitaxel/efeitos adversos
4.
Food Chem ; 330: 127241, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32540526

RESUMO

Curcumin (CUR) is a promising edible phytochemical compound with ideal ulcerative colitis (UC) treatment activity; however, it is characteristically instable in the digestive tract and has a short retention time in colon. Therefore, we designed and fabricated an oral food-grade nanocarrier composed of tannic acid (TA)-coated, Genipin (Gnp)-crosslinked human serum albumin (HSA) to encapsulate CUR (TA/CUR-NPs). The resulting CUR nanoparticles (NPs) were about 220 nm and -28.8 mV. With the assistance of TA layer and Gnp-crosslinking, the entire nano-scaled system effectively delayed CUR release in simulated gastric fluid, prolonged its colon adhesion and increased its uptake in Caco-2 cells. As expected, TA/CUR-NPs oral administration significantly alleviated colitis symptoms in DSS-treated mice when compared with controls by inhibiting the TLR4-linked NF-κB signaling pathway. Collectively, this study indicates that we have developed a convenient, eco-friendly, nano-scaled vehicle for oral delivery of CUR with anti-UC benefit.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Curcumina/química , Iridoides/química , Albumina Sérica Humana/química , Taninos/química , Administração Oral , Animais , Células CACO-2 , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química
5.
Int J Nanomedicine ; 15: 2699-2715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368050

RESUMO

Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.


Assuntos
Antivirais/farmacologia , Curcumina/farmacologia , Hepacivirus/efeitos dos fármacos , Nanopartículas/química , Antivirais/química , Linhagem Celular , Quitosana/química , Curcumina/administração & dosagem , Curcumina/química , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Humanos , Neoplasias Hepáticas/virologia , Nanopartículas/uso terapêutico , Proteínas do Core Viral/metabolismo , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
6.
Life Sci ; 256: 117840, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32450173

RESUMO

AIMS: Platelet production improvement can resolve concerns about the limitations of external platelet supply and platelet transfusion in thrombocytopenia patients. To this end, scientists encourage to induce the generation of megakaryocyte and platelet. Curcumin is a safe ingredient of turmeric that affects various cellular pathways. The effect of this component on platelet production has not been yet reported. MAIN METHODS: Our in vitro experiments include the investigation of the effects of nanocurcumin on megakaryocytes production from K562 cells and hematopoietic stem cells via megakaryocyte markers expression, DNA content, ROS, and morphologic analysis, and CFC assay. The regulatory functions of MAPKs pathways were also determined. In the in vivo study tissue distribution of nanocurcumin was determined and two treatment schedules were used to evaluate the capability of nanocurcumin to prevent the occurrence of Busulfan-induced thrombocytopenia in the mouse model. KEY FINDING: In vitro evidences demonstrated that nanocurcumin can induce MK production from K562 cells and hematopoietic stem cells. Inhibition of ERK1/2 and JNK pathways arrested this activity. In vivo experiments showed the uptake of nanocurcumin by tissues in mice. Administration of nanocurcumin could preserve bone marrow integrity and increase of the number of circulating platelets in the Busulfan-treated mice models. SIGNIFICANCE: Our results have demonstrated that nanocurcumin administration can be useful for the improvement of megakaryocytes and platelet generation in vitro. This component may be exerting these beneficial effects on megakaryopoiesis by modulating ERK1/2 and JNK pathways. As well as nanocurcumin has the potential to prevent thrombocytopenia in chemotherapy threated mice.


Assuntos
Plaquetas/efeitos dos fármacos , Curcumina/farmacologia , Megacariócitos/efeitos dos fármacos , Nanoestruturas , Trombocitopenia/prevenção & controle , Animais , Antineoplásicos Alquilantes/toxicidade , Plaquetas/metabolismo , Bussulfano/toxicidade , Curcumina/administração & dosagem , Curcumina/farmacocinética , Feminino , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Células K562 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Megacariócitos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Trombocitopenia/induzido quimicamente , Distribuição Tecidual
7.
Int J Nanomedicine ; 15: 3099-3120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431504

RESUMO

Curcumin, a yellow-colored polyphenol extracted from the rhizome of turmeric root, is commonly used as a spice and nutritional supplement. It exhibits many pharmacological activities such as anti-inflammatory, anti-bacterial, anti-cancer, anti-Alzheimer, and anti-fungal. However, the therapeutic application of curcumin is limited by its extremely low solubility in aqueous buffer, instability in body fluids, and rapid metabolism. Nano delivery system has shown excellent potential to improve the solubility, biocompatibility and therapeutic effect of curcumin. In this review, we focus on the recent development of nano encapsulated curcumin and its potential for biomedical applications.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Curcumina/química , Humanos , Lipossomos/química , Solubilidade
8.
Int J Nanomedicine ; 15: 2207-2217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280215

RESUMO

Background: Lipid-polymer hybrid nanoparticles (LPHNP) are suitable for co-delivery of hydrophilic and lipophilic drugs. The structural advantages of polymers and biomimetic properties of lipids enable higher encapsulation of drugs and controlled release profile. Lipid-polymer hybrid nanoparticles have been prepared for co-delivery of curcumin and cisplatin for enhanced cytotoxicity against ovarian cancer. Material and Methods: Chitosan, cisplatin, curcumin, Lipoid S75 were selected as structural components and ionic gelation method was used for preparation of LPHNPs. Nanoparticles were formed via ionic interaction of positively charged chitosan and negatively charged lipid. Results: The optimized nanoparticles were of 225 nm with cationic charge. The encapsulation efficiency was greater than 80% with good drug loading. The drug release profile showed controlled release behavior of both curcumin and cisplatin simultaneously and the absence of burst release. The in vitro therapeutic efficacy and cellular association was evaluated using A2780 ovarian cell lines. To further investigate therapeutic efficacy, we developed 3D spheroids as tumor model to mimic the in vivo conditions. The cytotoxicity and uptake of co-loaded LPHNPs were evaluated on 3D spheroids and results indicated increased chemosensitization and enhanced therapeutic efficacy of co-loaded LPHNPs. Conclusion: Lipid-polymer hybrid nanoparticles could be a suitable platform for co-delivery of curcumin and cisplatin for enhanced cytotoxic effect on ovarian cell lines.


Assuntos
Apoptose/efeitos dos fármacos , Quitosana/química , Cisplatino/administração & dosagem , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Curcumina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Esferoides Celulares/efeitos dos fármacos , Eletricidade Estática
9.
Int J Nanomedicine ; 15: 1853-1862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256064

RESUMO

Background: Curcumin has shown many pharmacological activities in both preclinical and clinical studies. Many technologies have been developed and applied to improve the solubility and bioavailability of curcumin, especially the nanotechnology-based delivery systems. However, there has been evidence that certain nanoparticles have potential reproductive toxicity in practice. Methods: Curcumin-poly (lactic-co-glycolic acid) (PLGA)-PEG nanoparticles (Cur-PLGA-NPs for short) were prepared. The Cur-PLGA-NPs were evaluated with its effect on the proliferation of mouse testicular cell lines in vitro and spermatogenesis in vivo, while PLGA-NPs were used as control. For animal experiments, male BALB/c mice were treated with 20 mg/kg of Cur-PLGA-NPs for continuous 10 days via tail vein injection. Results: We found the curcumin nanoparticles suppressed the proliferation of testicular cell lines in vitro. Furthermore, a short-term intravenous delivery of curcumin-loaded nanoparticles could be harmful to the differentiation of spermatogonia, the elongation of spermatids, as well as the motility of mature sperms. Conclusion: In the present study, we disclosed the acute damage on mouse spermatogenesis and sperm parameters by curcumin-loaded nanoparticles. Our results suggested that the reproductive toxicity of nanoformulated curcumin needs to be prudently evaluated before its application.


Assuntos
Curcumina/efeitos adversos , Nanopartículas/efeitos adversos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/química , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Células de Sertoli/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Espermatogônias/patologia , Espermatozoides/patologia
10.
Nutr Metab Cardiovasc Dis ; 30(4): 625-633, 2020 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-32127335

RESUMO

BACKGROUND AND AIMS: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. METHODS AND RESULTS: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50-80 years, body mass index: 25-40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. CONCLUSION: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. CLINICAL TRIAL REGISTRATION: ACTRN12616000732482p.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Curcumina/administração & dosagem , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Obesidade/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Sistema Cardiovascular/fisiopatologia , Curcumina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Óleos de Peixe/efeitos adversos , Nível de Saúde , Humanos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , New South Wales , Obesidade/diagnóstico , Obesidade/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
11.
Hum Cell ; 33(3): 730-736, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32146706

RESUMO

The present study investigated the antitumor activity and chemopreventive effects of a nanoparticle formulation of curcumin in preclinical models of mouse Pten-deficient prostate cancer. The antitumor activity of the nanoparticle curcumin was evaluated in mouse castration-naïve (7113-D3) and castration-resistant prostate cancer (2945-E10) derived cell lines in vitro. Cell viability was reduced in both cell lines in a dose and time-dependent manner. The effects of long-term dietary supplementation with the nanoparticle curcumin formulation were evaluated in a conditional Pten-deficient mouse model. Prostate tissues from Pten-deficient prostate cancers were obtained after sixteen weeks of dietary supplementation of 76 mg/kg/day or 380 mg/kg/day nanoparticle curcumin. Daily supplementation of nanoparticle curcumin did not affect mouse bodyweights or spleen size but did result in enlargement of the liver. Dietary supplementation did not influence tumor burden, however, mice fed high-dose curcumin had lower cancer cell proliferation rates at 12 and 16 weeks of age. Together, these results show that daily supplementation of a nanoparticle formulation of curcumin is tolerable and suggest that curcumin could have chemopreventive activity in early-stage prostate cancer.


Assuntos
Quimioprevenção , Curcumina/administração & dosagem , Nanopartículas , PTEN Fosfo-Hidrolase/deficiência , Neoplasias da Próstata/prevenção & controle , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Neoplasias da Próstata/etiologia
12.
Life Sci ; 249: 117515, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32147428

RESUMO

AIMS: This study investigated the effects of curcumin-loaded super-paramagnetic iron oxide (Fe3O4) nanoparticles (NPs) (SPIONs) on histological parameters and apoptosis-inducing factors (AIFs) in an experimental mouse model of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total number of 40 female prepuberal BALB/c mice were randomly divided into four groups. Group 1 was selected as control and Group 2 was considered as a vehicle taking sesame oil, in the form of a curcumin carrier. Moreover, Group 3 was administered with dehydroepiandrosterone (DHEA) at 6 mg/100 g of the body weight and Group 4 received the DHEA plus the NPs of curcumin (5.4 mg/100 g) for twenty consecutive days. Finally, histology, stereology, and apoptosis of the ovary were evaluated. KEY FINDINGS: The results revealed that the NPs of curcumin had reduced ovarian volume (p < 0.05) and a total number of primary, secondary, antral, and primordial follicles in comparison with the PCOS and vehicle groups (p < 0.05). Furthermore, curcumin treatment following administration of the DHEA resulted in a significant decrease in BAX (p < 0.001) and levels of expression of Caspase3 (CASP3) protein, increased levels of B-cell lymphoma 2 (Bcl2) expression (p < 0.05), and moderated apoptosis in granulosa cells in comparison with the ones seen in the PCOS group. SIGNIFICANCE: Ovarian injuries and DHEA-induced apoptosis were efficiently suppressed by curcumin, indicating the probable protective property of NPs of curcumin against PCOS.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Compostos Férricos/administração & dosagem , Nanopartículas Metálicas/química , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Maturidade Sexual , Animais , Antioxidantes/administração & dosagem , Apoptose/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Feminino , Compostos Férricos/química , Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Estresse Oxidativo
13.
Int J Nanomedicine ; 15: 1787-1796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214811

RESUMO

Introduction: Curcumin faces a major challenge in clinical use due to its poor aqueous solubility, which affects its bioavailability over oral use. The present study was carried out to overcome this problem. Methods: An amorphous micellar curcumin-spray dried powder (MC-SDP) with self-assembled casein was prepared by the addition of sucrose as a protectant. The dry powder of curcumin-loaded micelles was obtained by a spray-drying technique in the presence of sucrose as a protectant. The MC-SDP in the form of dry powder was further developed into tablets to investigate the dissolution profile. The physical properties of preformed powder were characterized by differential thermal analysis (DTA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Quantitative analysis in the form of solutions was analyzed by high-performance liquid chromatography (HPLC). Results: The physical properties demonstrated that MC-SDP varies from dented to smoother surfaces as a function of sucrose. Furthermore, melting transitions of curcumin in the form of MC-SDP were broadened in all sample mixtures, as observed in the DTA thermogram. The XRD spectra showed that the sharp and very intense peaks of single curcumin crystalline structure no longer existed in all MC-SDP forms, indicating that the mixtures were amorphous. Moreover, a further dissolution study of MC-SDP showed a significant increase of drug dissolved with the presence of sucrose, where >80% of curcumin from MC-SDP was dissolved within 30 min. Conclusion: The study demonstrated the manufacture of micellar spray-dried powder that would contribute to the development of oral delivery of curcumin.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Administração Oral , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Curcumina/farmacocinética , Composição de Medicamentos , Estabilidade de Medicamentos , Micelas , Microscopia Eletrônica de Varredura , Pós/química , Solubilidade
14.
Food Chem ; 319: 126577, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32172044

RESUMO

Many liposoluble nutrients are restricted for applications in foods due to their poor water solubility, stability and bioavailability. Here, a deamidated zein peptide with a broad molecular weight distribution and high carboxyl and hydrophobic residue contents was used to solubilize curcumin. The complex nanoparticles of curcumin and the peptide were produced through self-assembly in aqueous solutions. Fluorescence and infrared spectra revealed that hydrogen bonding and hydrophobic interactions actuated the assembly. The complex nanoparticles had a curcumin loading capacity of 31.9% and completely inhibited curcumin crystallization. The peptide effectively protected curcumin from decomposition in aqueous solutions by inhibiting the reaction between dissolved oxygen and curcumin. The nanoparticles presented excellent freeze-drying/re-dispersion stability without any lyoprotectant. The curcumin bioaccessibility of the nanoparticles was 75% and the nanoparticles exerted a significant antioxidant effect after oral administration in mice. This study indicates that the nanoparticles are potentially useful as an antioxidant additive in foods.


Assuntos
Curcumina/química , Curcumina/farmacocinética , Nanopartículas/química , Zeína/química , Administração Oral , Aminação , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Cristalização , Curcumina/administração & dosagem , Liofilização , Ligação de Hidrogênio , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos Endogâmicos ICR , Estabilidade Proteica , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Poult Sci ; 99(2): 1124-1134, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32036964

RESUMO

Curcumin has antioxidant functions, regulates the intestinal microbial composition, and alleviates mycotoxin toxicity. The present study aimed to explore whether curcumin could alleviate ochratoxin A (OTA)-induced liver injury via the intestinal microbiota. A total of 720 mixed-sex 1-day-old White Pekin ducklings were randomly assigned into 4 groups: CON (control group, without OTA), OTA (fed a diet with 2 mg/kg OTA), CUR (ducks fed a diet with 400 mg/kg curcumin), and OTA + CUR (2 mg/kg OTA plus 400 mg/kg curcumin). Each treatment consisted of 6 replicates and 30 ducklings per replicate. Treatment lasted for 21 D. Results were analyzed by a two-tailed Student t test between 2 groups. Our results demonstrated that OTA treatment had the highest serum low-density lipoprotein (LDL) level among 4 groups. Compared with OTA group, OTA + CUR decreased serum LDL level (P < 0.05). OTA decreased liver catalase (CAT) activity in ducks (P < 0.05), while addition of curcumin in OTA group increased liver CAT activity (P < 0.05). 16S ribosomal RNA sequencing suggested that curcumin increased the richness indices (ACE index) and diversity indices (Simpson index) compared with OTA group (P < 0.05) and recovered the OTA-induced alterations in composition of the intestinal microbiota. Curcumin supplementation relieved the decreased abundance of butyric acid producing bacteria, including blautia, butyricicoccus, and butyricimonas, induced by OTA (P < 0.05). OTA also significantly influenced the metabolism of the intestinal microbiota, such as tryptophan metabolism and glyceropholipid metabolism. Curcumin could alleviate the upregulation of oxidative stress pathways induced by OTA. OTA treatment also increased SREBP-1c expression (P < 0.05). The curcumin group had the lowest expression of FAS and PPARG mRNA (P < 0.05) and the highest expression of NRF2 and HMOX1 mRNA. These results indicated that curcumin could alleviate OTA-induced oxidative injury and lipid metabolism disruption by modulating the cecum microbiota.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/veterinária , Curcumina/farmacologia , Patos , Ocratoxinas/efeitos adversos , Venenos/efeitos adversos , Doenças das Aves Domésticas/prevenção & controle , Substâncias Protetoras/farmacologia , Ração Animal/análise , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Curcumina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Doenças das Aves Domésticas/etiologia , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória
16.
Int J Nanomedicine ; 15: 943-952, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103948

RESUMO

Background: Malignant pleural effusion (MPE) is the accumulation of fluid in the pleural cavity as a result of malignancies affecting the lung, pleura and mediastinal lymph nodes. Curcumin, a compound found in turmeric, has anti-cancer properties that could not only treat MPE accumulation but also reduce cancer burden. To our knowledge, direct administration of curcumin into the pleural cavity has never been reported, neither in animals nor in humans. Purpose: To explore the compartmental distribution, targeted pharmacokinetics and the safety profile of liposomal curcumin following intrapleural and intravenous administration. Methods: Liposomal curcumin (16 mg/kg) was administered into Fischer 344 rats by either intrapleural injection or intravenous infusion. The concentration of curcumin in plasma and tissues (lung, liver and diaphragm) were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Blood and tissues were examined for pathological changes. Results: No pleural or lung pathologies were observed following intrapleural liposomal curcumin administration. Total curcumin concentration peaked 1.5 hrs after the administration of intrapleural liposomal curcumin and red blood cell morphology appeared normal. A red blood cells abnormality (echinocytosis) was observed immediately and at 1.5 hrs after intravenous infusion of liposomal curcumin. Conclusion: These results indicate that liposomal curcumin is safe when administered directly into the pleural cavity and may represent a viable alternative to intravenous infusion in patients with pleural-based tumors.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Cavidade Pleural/efeitos dos fármacos , Administração Intravenosa , Animais , Cromatografia Líquida , Feminino , Lipossomos/administração & dosagem , Lipossomos/farmacocinética , Pulmão/efeitos dos fármacos , Masculino , Neoplasias Pleurais/patologia , Ratos Endogâmicos F344 , Espectrometria de Massas em Tandem , Distribuição Tecidual
17.
J Oleo Sci ; 69(2): 123-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023579

RESUMO

Curcumin is a bioactive compound with proven antioxidant and anti-inflammatory activities, but has low water solubility and dermal absorption. The inflammatory process is considered as the biological response to damage induced by various stimuli. If this process fails to self-regulate, it becomes a potential risk of cancer. The objective of this work was to evaluate the anti-inflammatory activity of curcumin administered to mice with induced atrial edema using two topical vehicles: organogels and O/W-type nanogels at pH 7, Organogels and O/W-type nanogels at pH 7 were prepared, characterized and the anti-inflammatory activity was assessed. A histopathological analysis of mouse ears was performed and two gel formulations were selected. Thermograms of organogels indicated that increasing the gelling agent improved the stability of the system. Deformation sweeps confirmed a viscoelastic behavior characteristic of gels in both systems. During the anti-inflammatory activity evaluations, the nanogels demonstrated greater activity (61.8 %) than organogels; Diclofenac® (2-(2,6-dichloranilino) phenylacetic acid), used as a control medication achieved the highest inhibition (85.4%); however, the drug produced the death of 2 (40%) of the study subjects caused by secondary adverse events. Histopathological analysis confirmed the data.


Assuntos
Anti-Inflamatórios , Cardiomiopatias/tratamento farmacológico , Curcumina/administração & dosagem , Curcumina/farmacologia , Portadores de Fármacos , Edema/tratamento farmacológico , Géis , Fitoterapia , Animais , Átrios do Coração , Camundongos
18.
Int J Nanomedicine ; 15: 1239-1252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110020

RESUMO

Introduction: Curcumin (Cur) is a natural extract of Asian spice Curcumin longa, showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue. Herein, we developed a self-assembled FA modified MPEG-PCL micelle to incorporate Cur (FA/Nano-Cur) and applied it for colorectal cancer therapy. Methods: We prepared FA/Nano-Cur micelles and identified their characteristics. The drug release behavior, pharmacokinetics and in vitro anti-tumor activities of FA/Nano-Cur were studied. Furthermore, the in vivo anti-tumor ability assessment and anti-tumor mechanisms investigation were carried out in murine colorectal cancer model. Results: FA/Nano-Cur micelles had an average particle size of 30.47 nm. Elongated T1/2 and larger AUC were found in FA/Nano-Cur group than that in the Free Cur group. MTT assay and apoptotic study indicated the growth inhibitory effect and pro-apoptotic effect of FA/Nano-Cur were the most significant among all treatments. Moreover, the in vivo study demonstrated that FA/Nano-Cur micelles exhibited a much stronger effect to suppress tumor growth, promote tumor apoptosis and attenuate tumor angiogenesis than Free Cur and Nano-Cur micelles. Conclusion: The present study demonstrated FA/Nano-Cur micelles might be a promising therapeutic agent in colorectal cancer treatment with distinctive advantages of improved bioavailability, sustained drug release, tumor-targeted delivery and low toxicity.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Curcumina/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Linhagem Celular Tumoral , Curcumina/farmacologia , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Ácido Fólico/química , Camundongos Endogâmicos BALB C , Micelas , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Ratos
19.
Complement Ther Med ; 48: 102267, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31987231

RESUMO

OBJECTIVE: The decline and eventual cessation of estrogen production cause a variety of symptoms during menopause, affecting each woman differently. Most women reported severe hot flashes and night sweats during menopause. The present study aimed to determine and compare the efficacy of curcumin and vitamin E on hot flashes and anxiety (primary objectives), sexual function, menopausal symptoms and adverse effects (secondary objectives). MATERIALS AND METHODS: This was a triple-blind randomized controlled clinical trial. The participants consisted of 93 postmenopausal women in Ahar city-Iran. They were assigned into three groups (two intervention groups and one control group). The first intervention group received oral capsule of curcumin (500 mg), the second intervention group was given oral tablets of vitamin E (200 IU/day), and the third group (control) received placebo twice a day for eight weeks. The participants completed the hot flash checklist one week before the intervention, and 4 weeks and 8 weeks after the intervention. They also filled out the Anxiety Scale, the Female Sexual Function Index (FSFI), the Greene Climacteric Scale before the intervention, and 4 weeks and 8 weeks after the intervention. One-way ANOVA, repeated measures ANOVA and ANCOVA tests were used for data analysis. RESULTS: There was no statistically significant difference between groups in terms of demographic characteristics, mean number of hot flashes, mean score of anxiety, sexual function index and menopausal symptoms before the intervention (p > 0.05). The mean age of participants was 51.7 years. Mean number of hot flashes in the curcumin group (adjusted mean difference = -10.7, 95%confidence interval = -3.6 to -17.9, P = 0.001) and in the vitamin E group (-8.7, -0.6 to -15.0, P = 0.029) was significantly lower than the placebo group after the intervention. The first significant effect of curcumin on hot flashes was observed after four weeks (P = 0.027). However, there was no significant difference between vitamin E group and placebo four weeks after intervention (P = 0.052) and the first significant effect of vitamin E on hot flashes was observed after eight weeks (P = 0.025). There was no statistically significant difference between the groups in terms of sexual function index, anxiety and menopausal symptoms (P > 0.05). CONCLUSION: The results of this study showed that oral intake of curcumin and vitamin E significantly reduced hot flashes in postmenopausal women but had no significant effect on anxiety, sexual function and menopausal symptoms.


Assuntos
Ansiedade/terapia , Curcumina/uso terapêutico , Fogachos/terapia , Pós-Menopausa/efeitos dos fármacos , Vitamina E/uso terapêutico , Administração Oral , Cápsulas , Curcumina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Vitamina E/administração & dosagem
20.
Molecules ; 25(2)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963196

RESUMO

Curcumin has been investigated extensively for cancer prevention, but it has been proposed that long-term treatments may promote clonal evolution and gain of cellular resistance, potentially rendering cancer cells less sensitive to future therapeutic interventions. Here, we used long-term, low-dose treatments to determine the potential for adverse effects in non-small cell lung cancer (NSCLC) cells. IC50s for curcumin, cisplatin, and pemetrexed in A549, PC9, and PC9ER NSCLC cells were evaluated using growth curves. IC50s were subsequently re-assessed following long-term, low-dose curcumin treatment and a three-month treatment withdrawal period, with a concurrent assessment of oncology-related protein expression. Doublet cisplatin/pemetrexed-resistant cell lines were created and the IC50 for curcumin was determined. Organotypic NSCLC-fibroblast co-culture models were used to assess the effects of curcumin on invasive capacity. Following long-term treatment/treatment withdrawal, there was no significant change in IC50s for the chemotherapy drugs, with chemotherapy-resistant cell lines exhibiting similar sensitivity to curcumin as their non-resistant counterparts. Curcumin (0.25-0.5 µM) was able to inhibit the invasion of both native and chemo-resistant NSCLC cells in the organotypic co-culture model. In summary, long-term curcumin treatment in models of NSCLC neither resulted in the acquisition of pro-carcinogenic phenotypes nor caused resistance to chemotherapy agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Curcumina/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fibroblastos , Humanos , Imuno-Histoquímica , Camundongos , Fatores de Tempo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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