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1.
Food Chem ; 352: 129395, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33677211

RESUMO

Myofibrillar proteins (MPs), as a food-grade material, have the potential to improve the solubility and bioavailability of curcumin. However, the interaction mechanism between MPs and curcumin under charge regulation induced by alkaline pH and NaCl was unclear. In this study, the binding between curcumin and MPs at pH 12 was confirmed by the fluorescence quenching under different NaCl concentration (0, 0.3, 0.6 and 0.9 mol/L). Further kinetic experiments showed, MPs possessed a higher affinity to bind curcumin in the presence of NaCl, especially at 0.6 M NaCl. Followed pH shifting from 12 to 7 does not affect UV-Vis absorption spectra of protein-curcumin dispersions. The secondary structure of MPs was not affected by binding with curcumin. Formation of this stable complex can be explained by hydrophobic other than electrostatic interaction. Therefore, the presence of NaCl facilitated exposure of hydrophobic pocket to improve the binding affinity between curcumin and MPs due to the importance of hydrophobic interaction.


Assuntos
Curcumina/metabolismo , Proteínas Musculares/metabolismo , Curcumina/química , Interações Hidrofóbicas e Hidrofílicas , Cinética , Proteínas Musculares/química , Ligação Proteica , Cloreto de Sódio/química , Solubilidade , Eletricidade Estática
2.
Sci Rep ; 11(1): 2043, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479401

RESUMO

The recent outbreak of the coronavirus (SARS-CoV2) is an unprecedented threat to human health and society across the globe. In this context, development of suitable interventions is the need of the hour. The viral spike protein (S Protein) and the cognate host cell receptor ACE2 can be considered as effective and appropriate targets for interventions. It is evident from the present computational study, that catechin and curcumin, not only exhibit strong binding affinity to viral S Protein and host receptor ACE2 but also to their complex (receptor-binding domain (RBD) of the spike protein of SARS-CoV2 and ACE2; RBD/ACE2-complex). The binding affinity values of catechin and curcumin for the S protein, ACE2 and RBD/ACE2-complex are - 10.5 and - 7.9 kcal/mol; - 8.9 and - 7.8 kcal/mol; and - 9.1 and - 7.6 kcal/mol, respectively. Curcumin directly binds to the receptor binding domain (RBD) of viral S Protein. Molecular simulation study over a period of 100 ns further substantiates that such interaction within RBD site of S Protein occurs during 40-100 ns out of 100 ns simulation trajectory. Contrary to this, catechin binds with amino acid residues present near the RBD site of S Protein and causes fluctuation in the amino acid residues of the RBD and its near proximity. Both catechin and curcumin bind the interface of 'RBD/ACE2-complex' and intervene in causing fluctuation of the alpha helices and beta-strands of the protein complex. Protein-protein interaction studies in presence of curcumin or catechin also corroborate the above findings suggesting the efficacy of these two polyphenols in hindering the formation of S Protein-ACE2 complex. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols for therapeutic strategy against SARS-CoV2.


Assuntos
/metabolismo , Catequina/metabolismo , Curcumina/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , /metabolismo , Catequina/química , Catequina/farmacologia , Membrana Celular/metabolismo , Biologia Computacional/métodos , Curcumina/química , Curcumina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/química
3.
Food Chem ; 347: 128978, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33444890

RESUMO

A safe and biodegradable γ-cyclodextrin-metal-organic-frameworks (γ-CD-MOFs) was successfully synthesized by using an improved hydrothermal method. In this study, curcumin (Cur) was chosen for testing the encapsulation stability and release performance of γ-CD-MOFs. Results of the crystal structure measurement indicated that the encapsulated curcumin within γ-CD-MOFs via van der Waals forces, hydrophobic interactions and hydrogen bonding was failed to disturb the inherent microtopography and crystallinity of γ-CD-MOFs. Compared to individual γ-CD, the γ-CD-MOFs exhibited improved loading capacity, physicochemical stability as well as controlled-release property in simulated digestion, and hence can be regarded as effective carriers for curcumin. Curcumin-loaded γ-CD-MOFs with a Cur : γ-CD-MOFs mass ratio of 2:3 (Cur-CD-MOFs/3), which showed the highest encapsulation efficiency (67.31 ± 2.25%), improved physicochemical stability and controlled-release performance, was selected for further research and industrialization. Our results demonstrate that γ-CD-MOFs can be regarded as a promising novel carrier for the delivery of curcumin or other hydrophobic nutraceuticals.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , gama-Ciclodextrinas/química , Curcumina/metabolismo , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Temperatura
4.
Life Sci ; 270: 119125, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33513394

RESUMO

AIMS: Human periodontal ligament stem cells (hPDLSCs) tether the teeth to the surrounding bone and are considered as major functional stem cells responsible for regeneration of the alveolar bone and periodontal ligament tissue. However, the outcome of stem cell regenerative therapy is affected by the survival rate and their differentiation potential of transplanted cells. This is primarily because of local oxidative stress and chronic inflammation at the transplantation site. Therefore, our study aimed to explore whether a natural antioxidant, curcumin could increase the tissue regeneration ability of transplanted hPDLSCs. MAIN METHODS: A hydrogen peroxide environment and a rat cranial bone defect model were built to mimic the oxidative stress conditions in vitro and in vivo, respectively. We evaluated the effect of curcumin on oxidative status, apoptosis, mitochondrial function and osteogenic differentiation of H2O2-stimulated hPDLSCs in vitro. We also measured the effect of curcumin on cell viability and bone repair ability of transplanted hPDLSCs in vivo. KEY FINDINGS: Our data showed that curcumin enhanced cell proliferation, reduced the reactive oxygen species (ROS) levels and apoptosis, maintained the standard mitochondrial structure and function, and promoted osteogenic differentiation of H2O2-stimulated hPDLSCs. The extracellular regulated protein kinases 1/2 (Erk1/2) signaling pathway was determined to be involved in the osteogenic differentiation of the H2O2-stimulated hPDLSCs. Moreover, curcumin enhanced the viability and the bone repair ability of hPDLSCs in vivo. SIGNIFICANCE: Curcumin reduced apoptosis and promoted osteogenesis of the hPDLSCs under oxidative stress, and might therefore have a potential clinical use with respect to tissue regeneration.


Assuntos
Curcumina/farmacologia , Ligamento Periodontal/metabolismo , Transplante de Células-Tronco/métodos , Animais , Apoptose/efeitos dos fármacos , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Curcumina/metabolismo , Feminino , Humanos , Ligamentos/metabolismo , Masculino , Dente Molar/metabolismo , Osteogênese/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Adulto Jovem
5.
Int J Mol Sci ; 22(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467433

RESUMO

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that regulate the expression of genes related to lipid and glucose metabolism and inflammation. There are three members: PPARα, PPARß or PPARγ. PPARγ have several ligands. The natural agonists are omega 9, curcumin, eicosanoids and others. Among the synthetic ligands, we highlight the thiazolidinediones, clinically used as an antidiabetic. Many of these studies involve natural or synthetic products in different pathologies. The mechanisms that regulate PPARγ involve post-translational modifications, such as phosphorylation, sumoylation and ubiquitination, among others. It is known that anti-inflammatory mechanisms involve the inhibition of other transcription factors, such as nuclear factor kB(NFκB), signal transducer and activator of transcription (STAT) or activator protein 1 (AP-1), or intracellular signaling proteins such as mitogen-activated protein (MAP) kinases. PPARγ transrepresses other transcription factors and consequently inhibits gene expression of inflammatory mediators, known as biomarkers for morbidity and mortality, leading to control of the exacerbated inflammation that occurs, for instance, in lung injury/acute respiratory distress. Many studies have shown the therapeutic potentials of PPARγ on pulmonary diseases. Herein, we describe activities of the PPARγ as a modulator of inflammation, focusing on lung injury and including definition and mechanisms of regulation, biological effects and molecular targets, and its role in lung diseases caused by inflammatory stimuli, bacteria and virus, and molecular-based therapy.


Assuntos
Inflamação/metabolismo , Pneumopatias/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/fisiologia , Animais , Curcumina/metabolismo , Curcumina/farmacologia , Eicosanoides/metabolismo , Eicosanoides/farmacologia , Humanos , Ligantes , Pneumopatias/tratamento farmacológico , PPAR gama/agonistas , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
Carbohydr Polym ; 254: 117446, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357916

RESUMO

Probiotics and curcumin can exhibit synergistic biological activities on the basis of a gut-brain axis, but are sensitive to environmental conditions, making it a challenge for their co-utilization. To meet the demand for high efficiency and convenience, both probiotics and curcumin were encapsulated within a propylene glycol alginate-based hydrogel delivery system, which was assembled using an ethanol-induced approach. The composite hydrogel was effective at sustaining the release of curcumin and protecting LGG cells in simulated gastrointestinal tract conditions. Moreover, it could also largely reduce the chemical degradation of curcumin and increase the survival of LGG during light exposure and long-term storage: up to 91.3 % of curcumin and 9.72 log CFU cm-3 remained present throughout 4 weeks of storage. Results in this work demonstrate a low-energy and green approach to assemble a composite hydrogel with remarkable biocompatibility, which is considered as a desired delivery vehicle for co-delivery of probiotics and curcumin.


Assuntos
Alginatos/química , Curcumina/metabolismo , Preparações de Ação Retardada , Lactobacillus rhamnosus/fisiologia , Lactoglobulinas/química , Probióticos/análise , Materiais Biomiméticos/química , Encapsulamento de Células/métodos , Curcumina/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Etanol/química , Suco Gástrico/química , Humanos , Hidrogéis , Concentração de Íons de Hidrogênio , Cinética , Lactobacillus rhamnosus/citologia , Soluções
7.
Int J Mol Sci ; 21(24)2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327438

RESUMO

Heme oxygenase (HO) is a critical component of the defense mechanism to a wide variety of cellular stressors. HO induction affords cellular protection through the breakdown of toxic heme into metabolites, helping preserve cellular integrity. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition by which the liver accumulates fat. The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic. NALFD can progress to nonalcoholic steatohepatitis (NASH), advancing further to liver cirrhosis or cancer. NAFLD is also a contributing factor to cardiovascular and metabolic diseases. There are currently no drugs to specifically treat NAFLD, with most treatments focused on lifestyle modifications. One emerging area for NAFLD treatment is the use of dietary supplements such as curcumin, pomegranate seed oil, milk thistle oil, cold-pressed Nigella Satvia oil, and resveratrol, among others. Recent studies have demonstrated that several of these natural dietary supplements attenuate hepatic lipid accumulation and fibrosis in NAFLD animal models. The beneficial actions of several of these compounds are associated with the induction of heme oxygenase-1 (HO-1). Thus, targeting HO-1 through dietary-supplements may be a useful therapeutic for NAFLD either alone or with lifestyle modifications.


Assuntos
Hepatopatia Gordurosa não Alcoólica/enzimologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Animais , Bilirrubina/metabolismo , Produtos Biológicos/metabolismo , Curcumina/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Resistência à Insulina/fisiologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Int J Mol Sci ; 22(1)2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33375513

RESUMO

Curcumin is a polyphenolic natural compound with diverse and attractive biological properties, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, Alzheimer's disease (AD), dementia, or mode disorders. AD is a chronic neurodegenerative disorder that is known as one of the rapidly growing diseases, especially in the elderly population. Moreover, being the eminent cause of dementia, posing problems for families, societies as well a severe burden on the economy. There are no effective drugs to cure AD. Although curcumin and its derivatives have shown properties that can be considered useful in inhibiting the hallmarks of AD, however, they have low bioavailability. Furthermore, to combat diagnostic and therapeutic limitations, various nanoformulations have also been recognized as theranostic agents that can also enhance the pharmacokinetic properties of curcumin and other bioactive compounds. Nanocarriers have shown beneficial properties to deliver curcumin and other nutritional compounds against the blood-brain barrier to efficiently distribute them in the brain. This review spotlights the role and effectiveness of curcumin and its derivatives in AD. Besides, the gut metabolism of curcumin and the effects of nanoparticles and their possible activity as diagnostic and therapeutic agents in AD also discussed.


Assuntos
Doença de Alzheimer/metabolismo , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Curcumina/análogos & derivados , Curcumina/metabolismo , Humanos , Nanoestruturas/uso terapêutico , Proteínas tau/metabolismo
9.
Life Sci ; 257: 118051, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634426

RESUMO

AIMS: Chemotherapy is an effective therapeutic modality which is commonly used for battling various cancers. However, several side effects induced by chemotherapeutic drugs would limit their clinical use. The present systematic review aims to evaluate the role of curcumin/curcuminoids co-administration during gastric cancer chemotherapy. METHODS: This systematic review was done according to PRISMA guidelines and a full systematic search in the electronic databases up to May 2020 using search terms in the titles and abstracts for the identification of relevant literature. 279 articles were found in electronic databases and 175 articles screened by title and abstract. Finally, 13 articles were included in this systematic review according to our inclusion and exclusion criteria. KEY FINDINGS: The findings indicated that gastric cancer chemotherapy induces cytotoxicity effects in various ways including a decrease of cell viability, colony formation, metastasis, tumor growth, and weight, as well as elevation of apoptosis pathway, oxidative stress pathway compared to the control group. Co-administration of curcumin/curcuminoids with chemotherapy synergistically increased the effects of anti-cancer chemotherapy compared to the group solo treated with chemotherapeutic agents. Also, in chemoresistance gastric cancer cells, co-administration of curcumin reduced chemoresistance mainly through the reduction of NF-κB activation and elevation of apoptosis. SIGNIFICANCE: According to the findings, the use of curcumin/curcuminoids during gastric cancer chemotherapy has chemosensitizing effects, and also it can reduce chemoresistance in gastric cancer.


Assuntos
Curcumina/uso terapêutico , Diarileptanoides/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/metabolismo , Curcumina/farmacologia , Diarileptanoides/metabolismo , Diarileptanoides/farmacologia , Tratamento Farmacológico/métodos , Humanos
10.
Life Sci ; 257: 117658, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621921

RESUMO

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.


Assuntos
Aterosclerose/tratamento farmacológico , Curcumina/farmacologia , Citomegalovirus/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Curcuma/metabolismo , Curcumina/metabolismo , Citocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Placa Aterosclerótica/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Aquat Toxicol ; 224: 105516, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32485495

RESUMO

Summer outbreaks of the hepatobiliary syndrome in fish impose a heavy burden on aquaculture in China. Curcumin is a polyphenol with antioxidant activity that has been used to protect the health of fish livers, but the mechanism underlying its protective effect is unclear. In this study, an in vitro model of hepatocyte oxidative damage in Oreochromis niloticus was established using H2O2. Treatment with 5 mM H2O2 for 2.5 h markedly reduced cell viability and antioxidant activity and elevated lactate dehydrogenase (LDH) activity, indicating conditions that can be used to establish an oxidative stress model. Under H2O2 stress, curcumin pretreatment significantly maintained cell viability, reduced malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. RNA-seq results showed that acute H2O2 treatment resulted in minor changes in gene expression, whereas curcumin changed the expression profile and affected cytochrome P450 (Cyp 450), glutathione (GSH) metabolism, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Several critical antioxidant defense signaling pathways were identified, and altered expression was confirmed by q-PCR. These results indicate that curcumin might upregulate PPAR expression by increasing Cyp2J2 expression. Further experiments showed that curcumin can upregulate the Nrf2-Keap1 signaling pathway at the transcriptional level, and this upregulation can induce downstream defense genes, including glutamate cysteine ligase catalytic subunit(GCLC) and glutamate cysteine ligase modifier subunit (GCLM), and thereby promote GSH synthesis and the expression of related antioxidases. This study might shed light on the effects of curcumin on the prevention and alleviation of liver diseases in fish.


Assuntos
Antioxidantes/farmacologia , Curcumina/farmacologia , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tilápia/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Células Cultivadas , Curcumina/metabolismo , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Hepatócitos/metabolismo , Peróxido de Hidrogênio/toxicidade , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/genética , Cultura Primária de Células , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tilápia/genética , Poluentes Químicos da Água/toxicidade
12.
Sci Rep ; 10(1): 7832, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398729

RESUMO

The traditional chemotherapy, including Adriamycin (Doxorubicin, DOX), is widely used and is part of the first-line chemotherapy of invasive B cell lymphoma. DOX is nonselective cytotoxic drug and has many adverse effects, which limit its clinical application in combination with other anti-cancer drugs. Optimization of the delivery system targeting tumor microenvironment could be a feasible approach that may have significant clinical significance. Further, combination of DOX with other anticancer drugs, such as curcumin, can enhance the synergistic effects, possibly through epigenetic mechanisms. Hence, we evaluated the efficacy and toxicity of novel nanoparticles that enable the co-delivery of DOX and curcumin in the treatment of invasive B cell lymphoma both in vivo and vitro. The polymer nano materials [mPEG-b-P(Glu-co-Phe)] was used to co-load DOX and curcumin (CUR): L-DOX + CUR. DOX signal was measured to determine the ability of the drugs entering the cells by flow cytometry, and the different enrichment areas in the cells were directly observed by confocal microscope. The toxicity of LDOX + CUR was tested by CCK-8 assay in different cells, and the synergistic coefficients were calculated. The cell apoptosis and the possible mechanisms of apoptosis pathways regulation by L-DOX + CUR were examined using flow cytometry and Western Blot. The MTD (maximum tolerable dose) test was performed in mice. Tumor-bearing SCID mice (i.e., BJAB cell) were used to evaluate the in vivo efficacy of L-DOX + CUR. L-DOX + CUR, was prepared successfully, and the mole ratio of DOX and CUR fixed in 1.0:1.2. (DOX loading rate 9.7%, CUR loading rate 8.1%). L-DOX + CUR exhibited increased intracellular delivery and the main enrichment area of DOX was nucleus. L-DOX + CUR increased cytotoxicity, induced higher rates of apoptosis, and had synergistic effect, especially in BJAB cells (min CI 0.019). It even had epigenetic effect and affected miRNA levels favorably by down-regulating miR-21, miR-199a and up-regulating miR-98 and miR-200c. Additionally, L-DOX + CUR increased MTD in Kunming mice (i.e., 25 mg/kg), compared to DOX (10 mg/kg) and L-DOX (20 mg/kg). In BJAB cell bearing SCID mice, L-DOX + CUR treatment suppressed tumor growth compared to DOX or L-DOX alone, and exhibited less weight loss in mice. We developed new polymer nanoparticles-mPEG-b-P (Glu-co-Phe) co-loaded with DOX and DUR. L-DOX + CUR exhibited synergistic cytotoxic and apoptotic effects on invasive B cell lymphoma. Treatment of L-DOX + CUR potentiated tumor killing in xenografts and reduced toxicity in vivo.


Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Linfoma/patologia , Nanoestruturas/química , Peptídeos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/química , Curcumina/metabolismo , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/metabolismo , Sinergismo Farmacológico , Endocitose , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Linfoma/tratamento farmacológico , Masculino , Camundongos , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Poult Sci ; 99(4): 2196-2202, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241505

RESUMO

This study was conducted to evaluate the effect of curcumin on laying performance, egg quality, biochemical indicators, hormone levels, and immune activity in hens under heat stress. Hy-Line brown hens (280-day-old) were fed with 0, 100, 150, and 200 mg/kg of curcumin during a 42-D experiment. Compared with the control treatment, supplementation with 150 mg/kg of curcumin improved laying performance and egg quality by significantly increasing egg production, eggshell thickness, eggshell strength (P < 0.01), and albumen height (P < 0.05) while decreasing the feed-to-egg ratio. Antioxidant activity was improved by significantly increasing the activity of superoxide dismutase and glutathione peroxidase but decreasing malondialdehyde levels in serum (P < 0.05) and significantly increasing the levels of follicle-stimulating hormone, luteinizing hormone, estradiol, IgG, IgA, and complement C3 activity in serum (P < 0.05). These results indicated that supplemental 150 mg/kg curcumin can improve productive performance, antioxidant enzyme activity, and immune function in laying hens under the heat stress conditions applied in the present study.


Assuntos
Galinhas/fisiologia , Curcumina/metabolismo , Resposta ao Choque Térmico , Hormônios/metabolismo , Imunidade/efeitos dos fármacos , Ração Animal/análise , Animais , Galinhas/sangue , Galinhas/imunologia , Curcumina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Feminino , Distribuição Aleatória
14.
Food Funct ; 11(2): 1684-1691, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32037431

RESUMO

Previous studies have shown that curcumin, a bioactive dietary compound with a thiol-reactive α,ß-unsaturated carbonyl moiety, can covalently modify protein thiols. However, most of the previous studies were performed in cultured cells or cell-free enzyme systems, and so it remains unknown whether curcumin could covalently modify proteins after oral administration in vivo. Using click chemistry-based fluorescence imaging, here we show that oral administration of dialkyne-curcumin (Di-Cur), a "click" probe mimicking curcumin, results in covalent modifications of cellular proteins in colon and liver tissues, but not in other tissues, in mice. This result suggests that oral administration of curcumin leads to the formation of the curcumin-protein complex in a tissue-specific manner, which could contribute to the biological effects and/or pharmacokinetics of curcumin. Further studies to elucidate the identities of curcumin-binding proteins could greatly help us to better understand the molecular mechanisms of curcumin, and develop novel strategies for disease prevention.


Assuntos
Química Click/métodos , Curcumina , Administração Oral , Animais , Linhagem Celular Tumoral , Colo/metabolismo , Curcumina/administração & dosagem , Curcumina/química , Curcumina/metabolismo , Curcumina/farmacocinética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sondas Moleculares , Ligação Proteica , Distribuição Tecidual
15.
Medicine (Baltimore) ; 99(2): e18467, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914018

RESUMO

BACKGROUND: Curcumin, a controversial "panacea," has been broadly studied. Its bioactivities including antioxidant, anti-inflammatory, and especially antineoplastic activities have been documented. However, due to its extensive bioactivities, some scientists hold a skeptical point of view toward curcumin and described curcumin as a "deceiver" to chemists. The objective of this study was to explore curcumin's another possibility as a potential supplementary leading compound to cancer treatments. METHODS: Literature searches were conducted using electronic databases. Search terms such as "curcumin," "curcumin analogues," and so on were used. The literatures were collected and summarized. In this article, reported targets of curcumin are reviewed. The limitations of a curcumin as a therapeutic anticancer product including low bioavailability and poor targeting are mentioned. Furthermore, modified curcumin analogues and antitumor mechanisms are listed and discussed in the aspects of cell death and tumor microenvironment including angiogenesis, tissue hypoxia status, and energy metabolism. RESULTS: Several possible modification strategies were presented by analyzing the relationships between the antitumor activity of curcumin analogues and their structural characteristics, including the introduction of hydrophilic group, shortening of redundant hydrocarbon chain, the introduction of extra chemical group, and so on. CONCLUSIONS: From our perspective, after structural modification curcumin could be more effective complementary product for cancer therapies by the enhancement of targeting abilities and the improvement of bioavailability.


Assuntos
Corantes/metabolismo , Corantes/farmacologia , Curcumina/metabolismo , Curcumina/farmacologia , Antineoplásicos , Disponibilidade Biológica , Morte Celular/efeitos dos fármacos , Terapias Complementares , Curcumina/química , Humanos , Neoplasias/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos
16.
Photochem Photobiol Sci ; 19(2): 193-206, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31956888

RESUMO

Photodynamic therapy (PDT) is a minimally invasive approach to treat various forms of cancer, based on the ability of certain non-toxic molecules (photosensitizers) to generate reactive oxygen species (ROS) after excitation by light of a certain wavelength and eventually induce strong phototoxic reactions against malignant cells and other pathogens. Curcumin is one of the most extensively investigated phytochemicals with a wide range of therapeutic properties and has been shown to induce strong photocytotoxic effects in micromolar concentrations against a variety of cancer cell lines. Curcumin (1) is comparatively evaluated with the naturally occurring bisdemethoxy Curcumin (2), which lacks the two methoxy groups, as well as two newly synthesized curcuminoids, the cinnamaldehyde derivative (3) and the dimethylamino one (4), designed to increase the absorption maximum and hence the tissue penetration. The synthetic curcuminoids were successfully synthesized in sufficient amounts and their photophysical properties such as absorption, fluorescence, photobleaching and free radical generation were investigated. Compound 4 exhibited a significant increase in peak absorption (497 nm) and strong fluorescent emission signals were recorded for all curcuminoids. Photobleaching of 4 was comparable to 1 whereas 2 and 3 showed more extended photobleaching but much higher ROS production in very short irradiation times. Compounds 2 and 4 exhibited specific intracellular localization. After dark and light cytotoxicity experiments against LNCaP prostate cancer cell line for all curcuminoids, concentration of 3 µM and irradiance of 6 mW cm-2 were selected for the PDT application which resulted in remarkable results with very short LD50. Curcuminoids 2 and 4 exhibited a significant dose-dependent PDT effect. The biphasic dose-response photodynamic effect observed for 1 and 3 may provide a strategy against prolonged and sustained photosensitivity.


Assuntos
Curcumina/análogos & derivados , Fotodegradação/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Curcumina/metabolismo , Curcumina/farmacologia , Humanos , Luz , Masculino , Microscopia Confocal , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/metabolismo
17.
Biochem Biophys Res Commun ; 524(1): 70-76, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31980182

RESUMO

Given the highly heterogeneity of diffuse large B cell lymphoma (DLBCL) and the diverse demands for proper treatment, many patients would relapse or show resistance to current therapeutic regimens, new treatment options are urgent to be explored. Curcumin harbored anti-tumor potential in various cancers, here, we investigated the possible effects and mechanism of curcumin on human DLBCL in vitro and in vivo, we found that curcumin inhibited cell viability in a concentration and time dependent manner, promoted cell apoptosis and arrested cell cycle at G2 phase, and these effects were mediated by PPARγ promotion and Akt/mTOR pathway inactivation. Furthermore, effects of curcumin on human DLBCL cells could be partly rescued by PPARγ antagonist GW9662, and enhanced by PPARγ agonist rosiglitazone. Taken together, our results demonstrated that curcumin inhibited the proliferation of DLBCL cells by up-regulating the expression of PPARγ, and our results might provide novel therapeutic approaches and a potential target to DLBCL treatment.


Assuntos
Antineoplásicos/metabolismo , Curcumina/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , PPAR gama/metabolismo , Anilidas/metabolismo , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos SCID , Neoplasias Experimentais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rosiglitazona/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
18.
ACS Appl Mater Interfaces ; 12(5): 5680-5694, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31944660

RESUMO

Photodynamic therapy (PDT), a clinically approved cancer treatment, has faced many drawbacks that restricted its applications. For example, the hypoxia-induced elevated hypoxia-inducible factor-1α (HIF-1α) may desensitize tumors to PDT, and the high concentration of glutathione (GSH) in cancer cells can also neutralize the generated reactive oxygen species (ROS) during PDT, resulting in insufficient therapy. Moreover, extra probes for imaging-guided visualization therapy are always needed to track drug release or distribution, while it may decrease the drug loading of the drug delivery system (DDS). In the present study, we have designed and prepared a novel multifunctional combined therapy nanoparticle (ZnPc@Cur-S-OA NPs), in which curcumin (Cur) was not only used as a chemotherapy drug to achieve a combination therapy with PDT via downregulating HIF-1α and depleting GSH in B16F10 cells but also designed as a small-molecule ROS-triggered release prodrug to deliver the photosensitizer (PS). The red fluorescence of PS in the nanoparticles (NPs) can be used to track the NPs distribution, while the green fluorescence of Cur showed an "OFF-ON" activation, which enables additional imaging and real-time self-monitoring capabilities. These results proved that the prepared combined therapy NPs were more effective to inhibit the growth of B16F10 mouse melanoma tumor than was monotherapy without eliciting systemic toxicity either in vitro or in vivo, which indicated the combined therapy NPs as an effective way to improve the PDT efficacy via downregulation of HIF-1α and depletion of GSH. Thus, the strategy of using a multifunctional natural product as the stimuli-responsive carrier as well as the synergist with PDT for enhancing antitumor efficacy via multiple pathways may open an alternative avenue to fabricate new self-delivery combination therapy nanodrugs. Besides, the fluorescence emitted from the drug can be used for real-time self-monitoring of drug release and distribution, which has great potential in clinic to adjust the administration dose and irradiation time for different tumor types and stages for individual therapy.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Glutationa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/metabolismo , Portadores de Fármacos/química , Lasers , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Biochem Pharmacol ; 173: 113820, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31972171

RESUMO

The present study was aimed to investigate the effects of curcumin, a representative chemopreventive phytochemical with pronounced antioxidant and anti-inflammatory properties, on activation of Nrf2 and expression of its target protein heme oxygenase-1 (HO-1) in mouse skin in vivo and in cultured murine epidermal cells. Treatment of mouse epidermal JB6 cells with curcumin resulted in the induction of HO-1 expression, and this was abrogated in cells transiently transfected with Nrf2 siRNA. While curcumin treatment increased protein expression of Nrf2, it did not alter the steady-state level of the Nrf2 mRNA transcript. Treatment of cells with curcumin stabilized Nrf2 by inhibiting ubiquitination and subsequent 26S proteasomal degradation of this transcription factor. Tetrahydrocurcumin, a non-electrophilic analogue of curcumin that lacks the α,ß-unsaturated carbonyl group, failed to induce HO-1 expression as well as nuclear translocation of Nrf2 and its binding to the antioxidant/electrophile response elements. Cells transfected with a mutant Keap1 protein in which cysteine 151 (Cys151) is replaced by serine exhibited marked reduction in curcumin-induced Nrf2 transactivation. Mass spectrometric analysis revealed that curcumin binds to Keap1 Cys151, supporting that this amino acid is a critical target for curcumin modification of Keap1, which facilitates the liberation of Nrf2. Thus, it is likely that the α,ß-unsaturated carbonyl moiety of curcumin is essential for its binding to Keap1 and stabilization of Nrf2 by hampering ubiquitination and proteasomal degradation.


Assuntos
Curcumina/farmacologia , Cisteína/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Curcumina/química , Curcumina/metabolismo , Embrião de Mamíferos/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Camundongos Knockout , Simulação de Acoplamento Molecular , Estrutura Molecular , Fator 2 Relacionado a NF-E2/química , Fator 2 Relacionado a NF-E2/genética , Ligação Proteica , Estabilidade Proteica/efeitos dos fármacos , Interferência de RNA , Pele/efeitos dos fármacos , Pele/metabolismo
20.
Colloids Surf B Biointerfaces ; 186: 110703, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31835185

RESUMO

Nanocrystals (NCs) have been introduced for use in pulmonary delivery in recent decades. Although the deposition and bioavailability have been extensively studied, little is known about the biofate, which influences the drug release and absorption process of NCs. In this study, we fabricated three different sized curcumin NCs by adjusting the parameters of mill machine using a wet milling method and studied the size effect on pulmonary absorption. The small nanocrystals (NC-S, 246.16 ±â€¯21.98 nm) exhibited a faster dissolution rate and higher diffusion percentage in vitro compared with middle (NC-M, 535.26 ±â€¯50.33 nm) and large nanocrystals (NC-L, 1089.53 ±â€¯194.34 nm). Multiple particle tracking experiments revealed that NC-S had larger mean squared displacement during diffusion in simulated mucus of 0.5% hydroxyethyl cellulose solution. Moreover, enhanced cellular uptake and transport efficiency were achieved by NC-S in Calu-3 cells and an air-liquid interface culturing model. NCs were mainly absorbed in the dissolved drug form, as assessed by using the Förster resonance energy transfer (FRET) technique. In vivo lung retention and distribution revealed that few smaller sized nanocrystals were retained in the lung after intratracheal administration. The pharmacokinetic study showed that the AUC(0-t) values of small sized nanocrystals were 1.75- and 3.32-fold greater than NC-M and NC-L, respectively. In conclusion, this study demonstrated that smaller sized nanocrystals were more easily absorbed into the blood system by increasing the dissolution rate.


Assuntos
Curcumina/metabolismo , Curcumina/farmacocinética , Sistemas de Liberação de Medicamentos , Pulmão/metabolismo , Nanopartículas/química , Mucosa Respiratória/metabolismo , Animais , Células Cultivadas , Curcumina/química , Liberação Controlada de Fármacos , Humanos , Pulmão/química , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Mucosa Respiratória/química , Solubilidade , Propriedades de Superfície , Distribuição Tecidual
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