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1.
Arch Biochem Biophys ; 690: 108446, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32593678

RESUMO

A simple NMR method to analyze the data obtained by NMR titration experiment of amyloid formation inhibitors against uniformly 15N-labeled amyloid-ß 1-42 peptide (Aß(1-42)) was described. By using solution nuclear magnetic resonance (NMR) measurement, the simplest method for monitoring the effects of Aß fibrilization inhibitors is the NMR chemical shift perturbation (CSP) experiment using 15N-labeled Aß(1-42). However, the flexible and dynamic nature of Aß(1-42) monomer may hamper the interpretation of CSP data. Here we introduced principal component analysis (PCA) for visualizing and analyzing NMR data of Aß(1-42) in the presence of amyloid inhibitors including high concentration osmolytes. We measured 1H-15N 2D spectra of Aß(1-42) at various temperatures as well as of Aß(1-42) with several inhibitors, and subjected all the data to PCA (PCA-HSQC). The PCA diagram succeeded in differentiating the various amyloid inhibitors, including epigallocatechin gallate (EGCg), rosmarinic acid (RA) and curcumin (CUR) from high concentration osmolytes. We hypothesized that the CSPs reflected the conformational equilibrium of intrinsically disordered Aß(1-42) induced by weak inhibitor binding rather than the specific molecular interactions.


Assuntos
Peptídeos beta-Amiloides/química , Fenóis/química , Análise de Componente Principal/métodos , Amiloide/metabolismo , Peptídeos beta-Amiloides/genética , Catequina/análogos & derivados , Catequina/química , Cinamatos/química , Curcumina/química , Depsídeos/química , Escherichia coli/genética , Humanos , Espectroscopia de Ressonância Magnética , Isótopos de Nitrogênio/química , Conformação Proteica , Temperatura , Termodinâmica
2.
AAPS PharmSciTech ; 21(5): 171, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32529560

RESUMO

Modifications to the surface chemistry, charge, and hydrophilicity/hydrophobicity of nanoparticles are applicable approaches to the alterations of the in vivo fate of intravenously administered nano-sized drug carriers. The objective of this study is to investigate the in vitro and in vivo antitumor efficacies of curcumin PLGA nanoparticles in relation to their surface structural modification via self-assembling coating with unique fungal hydrophobin. The hydophobin-coated curcumin PLGA nanoparticles (HPB PLGA NPs) were obtained by simply soaking curcumin-loaded PLGA nanoparticles (PLGA NPs) in aqueous fungal hydrophobin solution. The in vitro drug release behavior of the HPB PLGA NPS was also tested. The cytotoxicity and cellular uptake of these nanoparticles were determined in HepG2, A549, and Hela cell lines using MTT assay method and CLSM observation. The in vivo antitumor activity was evaluated in Hela tumor xenografted mice model. Compared with the PLGA NPs, the size and zeta potential of the nanoparticles were changed after hydrophobin coating, whereas similar in vitro release pattern was observed. The pharmacodynamics study showed prolonged blood retention of both nano-formulations than that of free curcumin, but no significant difference between the hydrophobin coated and uncoated nanoparticles. It was found that HPB PLGA NPs had increased cytotoxicities, higher cellular uptake, and improved antitumor efficacy. Surface modification of nanoparticles via self-assembling of hydrophobin is a convenient and promising method of changing particle surface physiochemical properties and antitumor performances. Further investigations, especially on tissue distribution, were needed to assess the potential application of the hydrophobin self-assembling coating in nano-drug delivery carriers.


Assuntos
Antineoplásicos/química , Curcumina/química , Fungos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Células A549 , Animais , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Curcumina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Células HeLa , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
3.
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
4.
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
5.
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
6.
Life Sci ; 251: 117627, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: covidwho-39610

RESUMO

AIMS: In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics. MATERIALS AND METHODS: Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated. KEY FINDINGS: COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV. SIGNIFICANCE: The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.


Assuntos
Antivirais/química , Betacoronavirus/enzimologia , Cisteína Endopeptidases/química , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Proteínas não Estruturais Virais/química , Sequência de Aminoácidos , Antivirais/farmacologia , Sítios de Ligação , Curcumina/química , Curcumina/farmacologia , Aprovação de Drogas , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Coronavírus da Síndrome Respiratória do Oriente Médio/enzimologia , Modelos Moleculares , Inibidores de Proteases/farmacologia , Vírus da SARS/enzimologia , Alinhamento de Sequência , Estados Unidos , United States Food and Drug Administration
7.
Life Sci ; 251: 117627, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251634

RESUMO

AIMS: In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics. MATERIALS AND METHODS: Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated. KEY FINDINGS: COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV. SIGNIFICANCE: The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.


Assuntos
Antivirais/química , Betacoronavirus/enzimologia , Cisteína Endopeptidases/química , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Proteínas não Estruturais Virais/química , Sequência de Aminoácidos , Antivirais/farmacologia , Sítios de Ligação , Curcumina/química , Curcumina/farmacologia , Aprovação de Drogas , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Coronavírus da Síndrome Respiratória do Oriente Médio/enzimologia , Modelos Moleculares , Inibidores de Proteases/farmacologia , Vírus da SARS/enzimologia , Alinhamento de Sequência , Estados Unidos , United States Food and Drug Administration
8.
Life Sci ; 253: 117588, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32220621

RESUMO

AIM: The present research work aimed to prepare and characterize nanoparticles of curcumin using polymers from different sources like natural, synthetic and semi-synthetic, and compare their activity for wound healing. Curcumin, BCS class II drug, is a polyphenol with proven wound healing activity. MATERIAL AND METHODS: The curcumin-loaded chitosan and carboxymethylcellulose (CMC) nanoparticles were prepared by ionotropic gelation method. In contrast, poly-lactic co-glycolic acid (PLGA) nanoparticles were prepared by a double emulsion solvent evapouration method. The different sources of polymers include natural (chitosan), synthetic (PLGA) and semi-synthetic CMC were used for the preparation of nanoparticles. KEY FINDINGS: The percentage entrapment efficiency of curcumin-loaded nanoparticles was found to be in the order of polymers PLGA>chitosan>CMC. The in-vitro release study of carboxymethyl cellulose -curcumin nanoparticles was found to be 74.96% for 24 h. The presence of a specific peak of curcumin in all the polymeric nanoparticles specifies drug incorporation in the polymeric matrix. The in-vivo study revealed that curcumin-loaded chitosan nanoparticles fasten the healing process of the wound due to the synergistic effect produced by using a combination of curcumin and chitosan. SIGNIFICANCE: Curcumin-loaded nanoparticles showed significant enhancement in wound healing action by lowering the dose of curcumin and effecting synergistically due to the use of chitosan.


Assuntos
Anti-Inflamatórios não Esteroides/química , Curcumina/química , Nanocápsulas/química , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Carboximetilcelulose Sódica/química , Quitosana/química , Curcumina/farmacologia , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões/química , Humanos , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar
9.
BMC Complement Med Ther ; 20(1): 68, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126993

RESUMO

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity. However, both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown. METHODS: To evaluate the growth inhibitory effects of CUR, DMC and BDMC on osteosarcoma (HOS and U2OS), breast (MDA-MB-231), and melanoma (A2058) cancer cells, we employed the MTT assay, annexin V-FITC /7-AAD staining, and clonogenic assay. RESULTS: CUR,DMC, and BDMC all decreased the viability of HOS, U2OS, MDA-MB-231, and A2058 cancer cells. Additionally, CUR,DMC, and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway. Furthermore, the combination of CUR,DMC, and BDMC synergistically reduced cell viability, colony formation and increased apoptosis than either two or a single agent in HOS cells. CONCLUSIONS: The combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.


Assuntos
Apoptose/efeitos dos fármacos , Diarileptanoides/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Smad/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacologia , Diarileptanoides/química , Quimioterapia Combinada , Humanos , Estrutura Molecular , Transdução de Sinais
10.
Food Chem ; 320: 126653, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32217430

RESUMO

Curcumin is claimed to have many health benefits, but it has low chemical stability. In this study, the influence of food-grade antioxidants on the chemical degradation of curcumin-enriched oil-in-water emulsions was examined. The curcumin degradation rate and extent depended on antioxidant type. The water-soluble antioxidants were more effective at protecting curcumin from degradation than the oil-soluble ones, which may have been because curcumin degrades faster in water than in oil. Interestingly, the amphiphilic antioxidant was almost as effective as the water-soluble ones. The oil-soluble antioxidant actually slightly promoted curcumin degradation. In summary, curcumin retention after storage declined in the following order: 82.6% (Trolox) ~82.2% (ascorbic acid) >79.5% (ascorbyl palmitate) ≫57.9% (control) >52.7% (α-tocopherol). The effectiveness of ascorbic acid in stabilizing curcumin increased as its concentration was raised (0-300 µM). Our results may facilitate the creation of curcumin-enriched foods and beverages with enhanced bioactivity.


Assuntos
Antioxidantes/química , Curcumina/química , Emulsões/química , Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/química , Cromanos/química , Óleos/química , Solubilidade , Água/química , alfa-Tocoferol/química
11.
Cancer Sci ; 111(5): 1785-1793, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32163218

RESUMO

The NF-kappa B (NF-κB) pathway plays a pivotal role in tumor progression and chemoresistance, and its inhibition has been shown to suppress tumor growth in a variety of preclinical models. Recently, we succeeded in synthesizing a water-soluble injectable type of curcumin ß-D-glucuronide (CMG), which is converted into a free-form of curcumin by ß-glucuronidase in vivo. Herein, we aimed to clarify the efficacy, safety and pharmacokinetics of CMG in a xenograft mouse model. First, we confirmed that the presence of KRAS/TP53 mutations significantly increased the IC50 of oxaliplatin (L-OHP) and NF-κB activity in HCT116 cells in vitro. Then, we tested the efficacy of CMG in an HCT116 colon cancer xenograft mice model. CMG demonstrated superior anticancer effects compared to L-OHP in an L-OHP-resistant xenograft model. With regard to safety, significant bodyweight loss, severe myelosuppression and AST/ALT elevation were observed in L-OHP-treated mice, whereas none of these toxicity was noted in CMG-treated mice. The combination of CMG and L-OHP exhibited additive effects in these xenograft models without increasing toxicity. Pharmacokinetic analysis revealed that high levels of free-form curcumin were maintained in the tumor tissue after 48 hours following CMG administration, but it was not detected in other major organs, such as the heart, liver and spleen. Immunohistochemistry revealed reduced NF-κB activity in the tumor tissue extracted from CMG-treated mice compared with that from control mice. These results indicated that CMG could be a promising anticancer prodrug for treating colon cancer with minimal toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Curcumina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glucuronídeos/uso terapêutico , Oxaliplatina/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Curcumina/uso terapêutico , Feminino , Glucuronidase/metabolismo , Glucuronídeos/química , Glucuronídeos/farmacocinética , Glucuronídeos/farmacologia , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Mutação , NF-kappa B/metabolismo , Oxaliplatina/uso terapêutico , Pró-Fármacos , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
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
13.
Phytother Res ; 34(8): 2067-2073, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32180294

RESUMO

Osteoarthritis is the most common articular disease that can lead to chronic pain and severe disability. Curcumin-an effective ingredient in turmeric with anti inflammatory property-plays an important role in protecting the joints against destructive factors. Gingerols and piperine, are the effective ingredients of ginger and black pepper, which may potentially enhance and sustain the effect of curcumin in this direction. To determine the effect of cosupplementation with turmeric extract, black pepper, and ginger on prostaglandin E2 (PGE2 ) in patients with chronic knee osteoarthritis, compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis (Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks. PGE2 was evaluated by ELISA method. 24-hr recall was also assessed. All of participants completed the study. PGE2 decreased significantly in both groups (p < .001), but there was no significant differences between groups. The results of this study indicated that intake of the selected herbs twice a day for 4 weeks may improve the PGE2 levels in patients with chronic knee osteoarthritis similar to Naproxen drug.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Curcuma/química , Curcumina/química , Gengibre/química , Naproxeno/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Piper nigrum/química , Extratos Vegetais/química , Anti-Inflamatórios não Esteroides/farmacologia , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naproxeno/farmacologia
14.
Phytother Res ; 34(8): 2074-2081, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32189385

RESUMO

The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM-induced increase in calcified nodule formation and osteogenesis-specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF-κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM-directed therapeutics for CAVD.


Assuntos
Estenose da Valva Aórtica/prevenção & controle , Valva Aórtica/patologia , Calcinose/prevenção & controle , Curcumina/química , Curcumina/uso terapêutico , NF-kappa B/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Valva Aórtica/efeitos dos fármacos , Curcumina/farmacologia , Cardiopatias Congênitas , Doenças das Valvas Cardíacas , Humanos
15.
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
16.
Food Chem ; 317: 126397, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078994

RESUMO

Curcumin/Hydroxypropyl-beta-Cyclodextrin (HP-ß-CyD) and Curcumin/Hydroxypropyl-gamma-Cyclodextrin (HP-γ-CyD) inclusion complex nanofibrous webs were produced using electrospinning technique for the purpose of orally fast-dissolving antioxidant food supplement. Curcumin was totally preserved without any loss during the electrospinning process. The aqueous solutions of curcumin/HP-ß-CyD and curcumin/HP-γ-CyD were yielded uniform fiber morphology with ~200 nm and ~900 nm average fiber diameter, respectively. Both Curcumin/CyD webs were produced in the form of free-standing and flexible character. Curcumin is a natural bioactive compound with poor water-solubility, however, the phase solubility test and dissolution/disintegration tests (water and artificial saliva) revealed that the water-solubility of curcumin was prominently improved by inclusion complexation with CyD. The antioxidant effect of curcumin in Curcumin/CyD webs was also enhanced due to higher solubility of curcumin by CyD inclusion complex. The results showed that HP-γ-CyD is significantly more effective than HP-ß-CyD in order to enhance the solubility and antioxidant property of curcumin in Curcumin/CyD webs.


Assuntos
Antioxidantes/farmacocinética , Curcumina/farmacocinética , Nanofibras/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Antioxidantes/química , Curcumina/química , Solubilidade , Água , gama-Ciclodextrinas/química
17.
J Agric Food Chem ; 68(9): 2795-2802, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32031786

RESUMO

Polydopamine (PDA) possesses high aqueous dispersibility, strong optical absorption, and a zwitterionic property, which give it multitudes of advantages to coat light-sensitive hydrophobic curcumin (Cur) for pH-responsive release. However, PDA is formed in alkaline conditions, which hinders its potential application for alkali-sensitive curcumin coating. Here, we developed a method to prepare PDA-coated Cur nanoparticles (NPs), which reduced chemical degradation of Cur in alkaline conditions. Encapsulation efficiency and loading capacity decreased to 73.69% and 51.80%, as the time for dopamine polymerization went on. PDA could protect Cur from light-induced degradation in powder and solution forms. Controlled release and pH-responsive delivery of PDA-coated Cur were observed under stomach and intestinal conditions compared to free Cur, which resulted from the coverage and thickness of the PDA shell and the electrostatic attraction between PDA and Cur. PDA-coated Cur NPs could be a promising way for the application of Cur in the beverage and food industry.


Assuntos
Curcumina/química , Indóis/química , Nanopartículas/química , Polímeros/química , Portadores de Fármacos/química , Composição de Medicamentos , Concentração de Íons de Hidrogênio , Cinética , Tamanho da Partícula
18.
Carbohydr Polym ; 231: 115745, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888811

RESUMO

Hydrogels are promising carriers for the controlled drug delivery in response to the external stimuli such as pH and temperature. Here, a new hydrogel is designed and synthesized from the cross-linking of graphene, chitosan, and cellulose nanowhisker via Schiff base reaction by a synthetic dialdehyde. The hydrogel presented a flexible structure and responded to altering pH and adding the external stimuli such as benzaldehyde and amino acid cysteine. The synthesized hydrogel was stable under physiological conditions. In vivo test showed that the hydrogel is subcutaneously injectable. Three drug-loaded hydrogels were synthesized, and in vitro drug release study showed a pH-dependent release of drugs in PBS solution.


Assuntos
Curcumina/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Benzaldeídos/química , Celulose/química , Celulose/farmacologia , Quitosana/química , Curcumina/farmacologia , Cisteína/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Grafite/química , Humanos , Concentração de Íons de Hidrogênio , Nanoestruturas/química , Temperatura
19.
Carbohydr Polym ; 231: 115714, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888845

RESUMO

Although supramolecular prodrug self-assemblies have been proven as efficient nanocarriers for cancer therapy, tedious synthesis procedures have made their practical applications more difficult. In this paper, ß-cyclodextrin-based supramolecular self-assemblies (SSAs) were directly constructed by utilizing ß-cyclodextrin trimer (ß-CD3) as the host unit and unmodified curcumin as the guest unit. Due to the adjustment of host-guest inclusion and hydrophilic-hydrophobic interactions occurring in the SSAs, their morphology could be readily tuned by changing the ratio of the two components. Different self-assembly morphologies, such as spherical complex micelles, spindle-like complex micelles and multi-compartment vesicles, were obtained. Furthermore, basic cell experiments were performed to study the corresponding effects of the SSA shape on their biological properties. Compared to the other micelles, the spindle-like complex micelles exhibited enhanced cellular toxicity, uptake behaviors and apoptosis rates, and the spherical complex micelles exhibited poor performance. The performance of the multi-compartment vesicles was similar to that of the spindle-like complex micelles. The facile construction of these shape-regulated SSAs and their different cellular biological properties might be valuable in the controlled drug release field.


Assuntos
Curcumina/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , beta-Ciclodextrinas/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Células MCF-7 , Micelas , Neoplasias , beta-Ciclodextrinas/farmacologia
20.
Biochem Pharmacol ; 173: 113790, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911090

RESUMO

Atopic diseases (atopic dermatitis, asthma and allergic rhinitis) affects a huge number of people around the world and their incidence rate is on rise. Atopic dermatitis (AD) is more prevalent in paediatric population which sensitizes an individual to develop allergic rhinitis and asthma later in life. The complex pathogenesis of these allergic diseases though involves numerous cellular signalling pathways but redox imbalance has been reported to be critical for induction/perpetuation of inflammatory process under such conditions. The realm of complementary and alternative medicine has gained greater attention because of the reported anti-oxidant/anti-inflammatory properties. Several case studies of treating atopic diseases with homeopathic remedies have provided positive results. Likewise, pre-clinical studies suggest that various natural compounds suppress allergic response via exhibiting their anti-oxidant potential. Despite the reported beneficial effects of phytochemicals in experimental model system, the clinical success has not been documented so far. It appears that poor absorption and bioavailability of natural compounds may be one of the reasons for realizing their full potential. The current paper throws light on impact of phytochemicals in the redox linked cellular and signalling pathways that may be critical in manifestation of atopic diseases. Further, an effort has been made to identify the gaps in the area so that future strategies could be evolved to exploit the medicinal value of various phytochemicals for an improved efficiency.


Assuntos
Asma/prevenção & controle , Dermatite Atópica/prevenção & controle , Hipersensibilidade/prevenção & controle , Compostos Fitoquímicos/uso terapêutico , Asma/imunologia , Asma/patologia , Catecóis/química , Catecóis/uso terapêutico , Curcumina/química , Curcumina/uso terapêutico , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Álcoois Graxos/química , Álcoois Graxos/uso terapêutico , Flavonoides/química , Flavonoides/uso terapêutico , Ginsenosídeos/química , Ginsenosídeos/uso terapêutico , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Estrutura Molecular , Compostos Fitoquímicos/química , Resveratrol/química , Resveratrol/uso terapêutico
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