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1.
Anticancer Res ; 40(1): 229-238, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892571

RESUMO

BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.


Assuntos
Neoplasias da Mama/patologia , Curcumina/farmacologia , Progressão da Doença , Naftoquinonas/farmacologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/uso terapêutico , Matriz Extracelular/metabolismo , Feminino , Humanos , Células MCF-7 , Naftoquinonas/química , Invasividade Neoplásica , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo
2.
Bioelectrochemistry ; 131: 107350, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31518962

RESUMO

Curcumin (Cur), the yellow pigment of well-known turmeric (Curcuma longa L.) is effective in multiple cancers including triple negative breast cancer (TNBC). In combination with electrical pulses (EP), enhanced effects of curcumin (Cur + EP) are observed in TNBC cells. To gain insights into the mechanisms of enhanced anticancer effects of Cur + EP, we studied the proteins involved in the anticancer activity of Cur + EP in MDA-MB-231, human TNBC cells using high-throughput global proteomics. A curcumin dose of 50 µM was applied with eight, 1200 V/cm, 100 µs pulses, the most commonly used electrochemotherapy (ECT) parameter in clinics. Results show that the Cur + EP treatment reduced the clonogenic ability in MDA-MB-231 cells, with the induction of apoptosis. Proteomic analysis identified a total of 1456 proteins, of which 453 proteins were differentially regulated, including kinases, heat shock proteins, transcription factors, structural proteins, and metabolic enzymes. Eight key glycolysis proteins (ALDOA, ENO2, LDHA, LDHB, PFKP, PGM1, PGAM1 and PGK1) were downregulated in Cur + EP from Cur. There was a switch in the metabolism with upregulation of 10 oxidative phosphorylation pathway proteins and 8 tricarboxylic acid (TCA) cycle proteins in the Cur + EP sample, compared to curcumin. These results provide novel systematic insights into the mechanisms of ECT with curcumin.


Assuntos
Antineoplásicos/uso terapêutico , Curcumina/uso terapêutico , Eletroquimioterapia/métodos , Proteínas de Neoplasias/metabolismo , Proteômica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Curcumina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Feminino , Glicólise , Humanos , Fosforilação Oxidativa , Via de Pentose Fosfato/efeitos dos fármacos , Reprodutibilidade dos Testes , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
3.
Life Sci ; 239: 117032, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31704450

RESUMO

Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. Curcumin analogues like IND-4, FLLL, GO-Y030 and C086 have demonstrated to produce greater cytotoxicity when experimentally studied and study results from many have been suggested to be the same. Combination of curcumin with therapeutic cancer agents like tolfenamic acid, 5-fluorouracil, resveratrol and dasatinib showed improved cytotoxicity and chemotherapeutic effect. The results propose that employment of curcumin with novel drug delivery systems like liposome, micelles and nanoparticle have been performed which could improve the therapeutic efficacy against colon cancer. The present review highlights the mechanism of action, synergistic effect and novel delivery methods to improve the therapeutic potential of curcumin.


Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , Curcumina/análogos & derivados , Curcumina/uso terapêutico , Humanos
5.
Eur J Med Chem ; 183: 111658, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514063

RESUMO

Cardiovascular disorders are known as one of the main health problems which are associated with mortality worldwide. Myocardial ischemia (MI) is improper blood supply to myocardium which leads from serious complications to life-threatening problems like AMI, atherosclerosis, hypertension, cardiac-hypertrophy as well as diabetic associated complications as diabetic atherosclerosis/cardiomyopathy/hypertension. Despite several efforts, the current therapeutic platforms are not related with significant results. Hence, it seems, developing novel therapies are required. In this regard, increasing evidences indicated, curcumin (CRC) acts as cardioprotective agent. Given that CRC and its analogs exert their cardioprotective effects via affecting on a variety of cardiovascular diseases-related mechanisms (i.e., Inflammation, and oxidative stress). Herein, for first time, we have highlighted the protective impacts of CRC against MI. This review might be a steppingstone for further investigation into the clinical implications of the CRC against MI. Furthermore, it pulls in light of a legitimate concern for scientific community, seeking novel techniques and characteristic dynamic biopharmaceuticals for use against myocardial ischemia.


Assuntos
Cardiotônicos/farmacologia , Curcumina/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Animais , Cardiotônicos/uso terapêutico , Curcumina/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos
6.
Int J Nanomedicine ; 14: 6425-6437, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496695

RESUMO

Introduction: Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity. Methods: The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied. Results: The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR. Conclusion: The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.


Assuntos
Alendronato/uso terapêutico , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Micelas , Osteossarcoma/tratamento farmacológico , Ácidos Esteáricos/química , Alendronato/química , Animais , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Curcumina/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Masculino , Camundongos Nus , Osteossarcoma/patologia , Tamanho da Partícula , Polímeros/química , Espectroscopia de Prótons por Ressonância Magnética
7.
C R Biol ; 342(5-6): 192-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474522

RESUMO

Exposure to lead is a threat factor for neurodegenerative disorders progress as it could trigger dopaminergic deficiency. We aimed herein to assess the effect of acute lead exposure (25mg/kg B.W i.p.) during three continuous days on the dopaminergic and noradrenergic systems together with locomotor performance in Meriones shawi (M. shawi), then the neuroprotective potential of curcumin-III (30mg/kg B.W) by oral gavage. Pb-exposed M. shawi exhibited increased tyrosine hydroxylase (TH) immunoreactivity in substantia nigra compacta (SNc), ventral tegmental area (VTA), locus coeruleus (LC), and dorsal striatum (DS), unlike the controls. This was correlated with decreased locomotor performance. A noticeable protective effect by co-treatment with curcumin-III was observed; in consequence, TH-immunoreactivity and locomotor disturbance were restored in Pb-treated Meriones. Our data results proved, on the one hand, an evident neurotoxic effect of acute Pb exposure and, on the other hand, a potent therapeutic effect of curcumin-III. Thereby, this compound may be recommended as a neuroprotective molecule for neurodegenerative disorders involving catecholaminergic impairment initiated by metallic elements.


Assuntos
Corpo Estriado/patologia , Curcumina/análogos & derivados , Neurônios Dopaminérgicos/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo/tratamento farmacológico , Intoxicação do Sistema Nervoso por Chumbo/patologia , Fármacos Neuroprotetores/uso terapêutico , Sistema Nervoso Parassimpático/patologia , Substância Negra/patologia , Administração Oral , Animais , Curcumina/uso terapêutico , Gerbillinae , Locus Cerúleo/patologia , Masculino , Transtornos dos Movimentos/psicologia , Área Tegmentar Ventral/patologia
8.
Int J Nanomedicine ; 14: 5073-5085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371948

RESUMO

Purpose: To potentiate the anticancer activity of curcumin (CUR) by improving its cell penetration potentials through formulating it into nanostructured lipid carriers (NLCs) and using the prepared NLCs in photodynamic therapy. Methods: A 3×4 factorial design was used to obtain 12 CUR-NLCs using two factors on different levels: (1) the solid lipid type at four levels and (2) the solid to liquid lipid ratio at three levels. Olive oil, Tween 80 and lecithin were chosen as liquid lipid, surfactant and co-surfactant, respectively. CUR-NLCs prepared by high shear hot homogenization method were evaluated by determination of particle size (PS), polydispersity index, zeta potential (ZP), entrapment efficiency percent, drug loading percent and in vitro drug release. Optimization was based on the evaluation results using response surface modeling (RSM). Optimized formulae were tested for their in vitro release pattern and for dark and photo-cytotoxic anticancer activity on breast cancer cell line in comparison to free CUR. Results: Evaluation tests showed the appropriateness of NLCs prepared from glyceryl monooleate and Geleol™ helped choosing two optimized formulae, PE3 and GE3. PE3 (prepared using glyceryl monooleate) showed enhanced release rates compared to GE3 (prepared from Geleol) and superior cytotoxic anticancer activity compared to both GE3 and free CUR under both light and dark conditions. The small mean PS, spherical shape as well as the negative ZP enhanced the internalization of the NLCs within cells. Modulation and inhibition of P-glycoprotein expression by glyceryl monooleate synergized the cytotoxic activity of CUR. Conclusion: CUR loading in NLCs enhanced its cell penetration and cytotoxic anticancer properties both in dark and in light conditions.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Curcumina/uso terapêutico , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Ácidos Oleicos/química , Azeite de Oliva/química , Fotoquimioterapia , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Células MCF-7 , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Eletricidade Estática
9.
Int J Nanomedicine ; 14: 4449-4460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417253

RESUMO

Curcumin as a hydrophobic polyphenol is extracted from the rhizome of Curcuma longa. Curcumin is widely used as a dietary spice and a topical medication for the treatment of inflammatory disorders in Asia. This compound also possesses remarkable anti-inflammatory and neuroprotective effects with the ability to pass from the blood brain barrier. Based on several pharmacological activities of curcumin, it has been introduced as an ideal candidate for different neurological disorders. Despite the pleiotropic activities of curcumin, poor solubility, rapid clearance and low stability have limited its clinical application. In recent years, nano-based drug delivery system has effectively improved the aqueous solubility and bioavailability of curcumin. In this review article, the effects of curcumin nanoparticles and their possible mechanism/s of action has been elucidated in various central nervous system (CNS)-related diseases including Parkinson's disease, Huntington disease, Alzheimer's disease, Multiple sclerosis, epilepsy and Amyotrophic Lateral Sclerosis. Furthermore, recent evidences about administration of nano-curcumin in the clinical trial phase have been described in the present review article.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Curcumina/uso terapêutico , Nanopartículas/química , Ensaios Clínicos como Assunto , Curcumina/administração & dosagem , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Fármacos Neuroprotetores/uso terapêutico
10.
Phytother Res ; 33(11): 2798-2820, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31429161

RESUMO

Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti-inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English-language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis-induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.


Assuntos
Curcumina/uso terapêutico , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Curcuma/química , Curcuma/fisiologia , Curcumina/farmacologia , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Humanos , Fitoterapia , Transdução de Sinais/efeitos dos fármacos
11.
Oxid Med Cell Longev ; 2019: 9372182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396308

RESUMO

The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) triggers the first line of homeostatic responses against a plethora of environmental or endogenous deviations in redox metabolism, proteostasis, inflammation, etc. Therefore, pharmacological activation of NRF2 is a promising therapeutic approach for several chronic diseases that are underlined by oxidative stress and inflammation, such as neurodegenerative, cardiovascular, and metabolic diseases. A particular case is cancer, where NRF2 confers a survival advantage to constituted tumors, and therefore, NRF2 inhibition is desired. This review describes the electrophilic and nonelectrophilic NRF2 activators with clinical projection in various chronic diseases. We also analyze the status of NRF2 inhibitors, which at this time provide proof of concept for blocking NRF2 activity in cancer therapy.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Ensaios Clínicos como Assunto , Curcumina/química , Curcumina/uso terapêutico , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo , Triterpenos/química , Triterpenos/uso terapêutico
12.
Int J Mol Sci ; 20(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374813

RESUMO

The efficacy of the plant-derived polyphenol curcumin, in various aspects of health and wellbeing, are a matter of public interest. An internet search of the term "Curcumin" displays about 12 million hits. Among the multitudinous information presented on partly doubtful websites, there are reports attracting the reader with promises ranging from eternal youth to cures for incurable diseases. Unfortunately, many of these reports are not based on scientific evidence, but they feed the desideratum of the reader for a "miracle cure". This circumstance makes it very difficult for researchers, whose work is scientifically sound and evidence is based on the therapeutic benefits (or side effects) of curcumin, to demarcate their results from sensational reports that circulate in the web and in other media. This is only one of many obstacles making it difficult to pave curcumin's way into clinical application; others are its nonpatentability and low economic usability. A further impediment comes from scientists who never worked with curcumin or any other natural plant-derived compound in their own labs. They have never tested these compounds in any scientific assay, neither in vitro nor in vivo; however, they claim, in a sometimes polemic manner, that everything that has so far been published on curcumin's molecular effects is based on artefacts. The here presented Special Issue comprises a collection of five scientifically sound articles and nine reviews reporting on the therapeutic benefits and the molecular mechanisms of curcumin or of chemically modified curcumin in various diseases ranging from malignant tumors to chronic diseases, microbial infection, and even neurodegenerative diseases. The excellent results of the scientific projects that underlie the five original papers give reason to hope that curcumin will be part of novel treatment strategies in the near future-either as monotherapy or in combination with other drugs or therapeutic applications.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Curcumina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Curcumina/farmacologia , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia
13.
Medicina (Kaunas) ; 55(7)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295875

RESUMO

Curcumin is a hydrophobic polyphenol compound extracted from the rhizome of turmeric. The protective effect of curcumin on kidney damage in multiple experimental models has been widely described. Its protective effect is mainly associated with its antioxidant and anti-inflammatory properties, as well as with mitochondrial function maintenance. On the other hand, occupational or environmental exposure to heavy metals is a serious public health problem. For a long time, heavy metals-induced nephrotoxicity was mainly associated with reactive oxygen species overproduction and loss of endogenous antioxidant activity. However, recent studies have shown that in addition to oxidative stress, heavy metals also suppress the autophagy flux, enhancing cell damage. Thus, natural compounds with the ability to modulate and restore autophagy flux represent a promising new therapeutic strategy. Furthermore, it has been reported in other renal damage models that curcumin's nephroprotective effects are related to its ability to regulate autophagic flow. The data indicate that curcumin modulates autophagy by classic signaling pathways (suppression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and/or by stimulation of adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-dependent kinase (ERK) pathways). Moreover, it allows lysosomal function preservation, which is crucial for the later stage of autophagy. However, future studies of autophagy modulation by curcumin in heavy metals-induced autophagy flux impairment are still needed.


Assuntos
Autofagia/fisiologia , Curcumina/farmacologia , Rim/fisiopatologia , Metais Pesados/efeitos adversos , Fatores de Proteção , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Arsênico/efeitos adversos , Cádmio/efeitos adversos , Cromo/efeitos adversos , Curcumina/uso terapêutico , Humanos , Rim/química , Rim/patologia , Chumbo/efeitos adversos , Mercúrio/efeitos adversos
14.
J Exp Clin Cancer Res ; 38(1): 323, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331376

RESUMO

Numerous studies have presented that curcumin could have a positive effect in the prevention of cancer and then in tumor therapy. Several hypotheses have highlighted that curcumin could decreases tumor growth and invasion by acting on both chronic inflammation and oxidative stress. This review focuses on the interest of use curcumin in cancer therapy by acting on the WNT/ß-catenin pathway to repress chronic inflammation and oxidative stress. In the cancer process, one of the major signaling pathways involved is the WNT/ß-catenin pathway, which appears to be upregulated. Curcumin administration participates to the downregulation of the WNT/ß-catenin pathway and thus, through this action, in tumor growth control. Curcumin act as PPARγ agonists. The WNT/ß-catenin pathway and PPARγ act in an opposed manner. Chronic inflammation, oxidative stress and circadian clock disruption are common and co-substantial pathological processes accompanying and promoting cancers. Circadian clock disruption related to the upregulation of the WNT/ß-catenin pathway is involved in cancers. By stimulating PPARγ expression, curcumin can control circadian clocks through the regulation of many key circadian genes. The administration of curcumin in cancer treatment would thus appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/ß-catenin pathway and PPARγ activity levels.


Assuntos
Curcumina/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , PPAR gama/genética , Proliferação de Células/efeitos dos fármacos , Relógios Circadianos/efeitos dos fármacos , Relógios Circadianos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos
15.
Mol Med Rep ; 20(3): 2332-2338, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322200

RESUMO

Benign thyroid nodules are among the most common endocrine disorders. Recent advances in diagnostic imaging and pathology have significantly contributed to better risk stratification of thyroid nodules. However, current treatment options, beyond surgical approaches are limited. The following placebo-controlled study presents, to the best of our knowledge, the first results of a non-invasive therapy for benign thyroid nodules. The efficacy and safety of a supplement containing spirulina, curcumin and Boswellia in euthyroid patients with benign thyroid nodules, was assessed by a 3 month, double-blind, placebo-controlled study which was completed by 34 patients. Patients with benign (FNAB documented) single thyroid nodules between 2 and 5 cm were evaluated in a prospective placebo-controlled cross-over trial, across 12 weeks (3 visits with six-week intervals). At each visit, the target thyroid nodule was recorded in two dimensions. In addition, plasma levels of thyroid stimulating hormone, free thyroxine and copper were assessed. The mean initial nodule area at V1 was 4.38±3.14 cm2, at V2 3.87±2.79 cm2, and at V3 3.53±2.84 cm2; P<0.04. Administration of the active substances (n=34) was followed by a mean area decrease of 0.611 cm2±0.933 (SD), while placebo administration (n=29) was followed by a mean decrease of 0.178 cm2±0.515 (SD), (P=0.027). The presented findings suggest that the combination of spirulina-curcumin-Βoswellia is effective in reducing the size of benign thyroid nodules. However, additional studies are needed in order to elucidate the exact mechanisms through which the suggested supplement facilitates a decrease in the size of benign thyroid nodules.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Boswellia , Curcumina/uso terapêutico , Spirulina , Nódulo da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/química , Boswellia/química , Curcumina/química , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Extratos Vegetais/uso terapêutico , Spirulina/química , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/sangue , Nódulo da Glândula Tireoide/patologia , Tireotropina/sangue , Tiroxina/sangue
16.
Appl Microbiol Biotechnol ; 103(18): 7481-7490, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300853

RESUMO

Cutaneous leishmaniasis being a neglected tropical disease (NTD) faces several challenges in chemotherapy. If infected with secondary bacterial infections, the treatment regime of cutaneous ulcers in cutaneous leishmaniasis is further complicated which usually require two or more than two chemotherapeutic agents for healing. In the current study, seven curcumin-loaded self-emulsifying drug delivery system (cu-SEDDS) formulations (namely F1-F7) were prepared by mixing different excipients (oils, surfactants, and co-solvents) through stirring (vortex) and sonication. The formulations were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential by zeta sizer. The cu-SEDDS formulations displayed different sizes ranging from 32.4 up to 80.0 nm. The zeta potential of the formulations ranged from - 1.56 up to - 4.8. The antileishmanial activities of the cu-SEDDS formulations in terms of IC50 against Leishmania tropica ranged from 0.19 up to 0.37 µg/ml. The minimum inhibitory concentrations (MICs) of these formulations against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae were in the range of 48-62 µg/ml. The hemolysis caused by formulations was 1-2%. The spreading potential of the formulations (F1 and F5) over damaged skin model was remarkable. These results suggest that cu-SEDDS further enhanced the broad spectrum antileishmanial and antibacterial profile of curcumin and could be used for the treatment of cutaneous leishmaniasis and its associated secondary infections.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Coinfecção/tratamento farmacológico , Curcumina/uso terapêutico , Emulsões/química , Leishmaniose Cutânea/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Infecções Bacterianas/parasitologia , Química Farmacêutica , Coinfecção/microbiologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Emulsões/uso terapêutico , Excipientes , Humanos , Leishmaniose Cutânea/complicações , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Pseudomonas aeruginosa/efeitos dos fármacos , Solubilidade , Staphylococcus aureus/efeitos dos fármacos
17.
Turk Neurosurg ; 29(3): 440-444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31270796

RESUMO

AIM: To clarify the effects of topical application of curcumin on the prevention of epidural fibrosis. MATERIAL AND METHODS: Twenty-one rats were randomly divided into three equal groups (control, spongostan, local curcumin) and a laminectomy procedure was performed between T11 and L1 in all rats. Subsequently, spongostan soaked with curcumin (100 mg/kg) was applied topically. After four weeks, the vertebral column from T9 to L3, which included the paraspinal muscles and epidural scar tissue, was removed as a single piece and the epidural fibrosis and arachnoidal scarring were graded and histopathological analysis carried out accordingly. Kruskal-Wallis and Pearson Chi-Square tests were used for statistical analysis. A p-value of less than 0.05 was considered to be significant. RESULTS: The grading of epidural fibrosis was far lower in the experimental group with curcumin compared to the control and spongostan groups, but the difference was not statistically significant. CONCLUSION: The findings of this study show that local curcumin decreases the formation of epidural fibrosis and this effect of curcumin is thought to be mediated by reducing the functions of inflammatory cells such as macrophages, neutrophils and fibroblasts, and the anti-inflammatory and antioxidant effects.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Espaço Epidural/efeitos dos fármacos , Espaço Epidural/patologia , Laminectomia/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatriz/patologia , Curcumina/uso terapêutico , Feminino , Fibrose/tratamento farmacológico , Fibrose/etiologia , Fibrose/patologia , Laminectomia/tendências , Modelos Animais , Ratos , Ratos Wistar , Resultado do Tratamento
18.
Neurochem Res ; 44(8): 2020-2029, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264110

RESUMO

The neurotoxic effects of aluminum are generally associated with reduced antioxidant capacity, increased oxidative stress and apoptosis, which lead to the induction of neurodegenerative processes. Curcumin has a lipophilic polyphenol character and effects of antioxidant and anti-apoptotic. The present study was undertaken to examine possible aluminum exposure in rats brain synaptosomes and to investigate whether protective and therapeutic effects of curcumin on biochemical and morphological changes in both pre- and post-treated groups. Aluminum chloride (AlCl3) at 50 µM concentration and curcumin at 5 and 10 µg/mL doses were applied to hippocampal synaptosomes of rats according to experimental design. Biochemical effects were evaluated by MTT cytotoxicity, malondialdehyde (MDA) levels, nitric oxide (NO) levels, glutathione (GSH) levels, caspase 3 activities, cytochrome c levels, DNA fragmentation values and protein levels. Morphological examinations were done by TEM analysis. AlCI3 exposure in the synaptosomes enhanced oxidative stress, triggered apoptosis and caused ultrastructural alterations which were well reflected in the TEM images. Curcumin pre-treatment slightly ameliorated the MDA levels, NO levels, cytochrome c levels and caspase 3 activities in AlCI3-exposed synaptosomes, but these results were not statistically significant. Furthermore, curcumin post-treatment significantly improved oxidative damage and morphological alterations, and suppressed cytochrome c and caspase 3 activities. Taken together, our data showed that curcumin had more therapeutic effects than protective effects in AlCI3-induced neurotoxicity. Nevertheless, the therapeutic (post-protective) effects of curcumin should be further investigated in in vivo neurodegenerative models involving behavioral tests.


Assuntos
Alumínio/efeitos adversos , Curcumina/uso terapêutico , Hipocampo/efeitos dos fármacos , Síndromes Neurotóxicas/tratamento farmacológico , Sinaptossomos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/prevenção & controle , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
19.
Chem Pharm Bull (Tokyo) ; 67(7): 648-653, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257320

RESUMO

Diabetic embryopathy is a diabetic complication, in which maternal hyperglycemia in early pregnancy causes birth defects in newborn infants. Under maternal diabetic conditions, hyperglycemia disturbs intracellular molecular activities and organelles functions. These include protein misfolding in the endoplasmic reticulum (ER), overproduction of reactive oxygen species (ROS) in mitochondria, and high levels of nitric oxide (NO). The resultant ER, oxidative, and nitrosative stresses activate apoptotic machinery to cause cell death in the embryo, ultimately resulting in developmental malformations. Based on the basic research data, efforts have been made to develop interventional strategies to alleviate the stress conditions and to reduce embryonic malformations. One of the challenges in birth defect prevention is to identify effective and safe agents to be used in pregnancy. One approach is to search and characterize naturally occurring phytochemicals, including flavonoids, curcuminoids and stilbenoids, for use in prevention of diabetic embryopathy.


Assuntos
Anormalidades Congênitas/prevenção & controle , Compostos Fitoquímicos/uso terapêutico , Gravidez em Diabéticas/prevenção & controle , Curcumina/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Gravidez , Estilbenos/química , Estilbenos/farmacologia , Estilbenos/uso terapêutico
20.
Drug Des Devel Ther ; 13: 2205-2213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308632

RESUMO

Introduction: In this study, novel folic acid (FA)-modified curcumin (CUR) liposomes (LPs) were developed and evaluated for their antitumor activity in vitro and in vivo. Methods: Characterization of the LPs, including transmission electron microscopy, morphology, particle size, and zeta potential studies, was carried out. Drug entrapment efficiency, drug-loading capacity, and release properties in vitro were tested. The in vitro growth inhibition activity, cellular uptake efficiency, and cell apoptosis of FA-modified CUR LPs were also investigated by a cervical cancer HeLa cell model. Results: The optimized distearoyl-l-a-phosphatidylethanolamine (DSPE)-PEG2000-FA-LPs/CUR formed spherical vesicles of nanometer sizes and had particle sizes of 112.3±4.6 nm, polydispersity index of 0.19±0.03, and zeta potential of -15.3±1.4 mV. In addition, the EE% and DL% of (DSPE)-PEG2000-FA-LPs/CUR were 87.6% and 7.9%, respectively. Compared with the free drug, FA-modified CUR LPs had sustained-release properties in vitro. In vivo, a strong green fluorescence was observed in the cytoplasmic region after incubation of (DSPE)-PEG2000-FA-LPs/CUR for 2 hrs. Conclusion: (DSPE)-PEG2000-FA-LPs/CUR showed a superior antiproliferative effect on HeLa cells and had a better antitumor effect in vivo than the non-modified LPs. These results indicated that (DSPE)-PEG2000-FA-LPs/CUR was a promising candidate for antitumor drug delivery.


Assuntos
Antineoplásicos/uso terapêutico , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Ratos , Propriedades de Superfície , Neoplasias do Colo do Útero/patologia
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