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1.
Nutr Cancer ; 72(3): 504-512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31290695

RESUMO

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Fabaceae/química , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/patologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Feminino , Ácido Gálico/metabolismo , Células HeLa , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fenóis/química , Quercetina/química
2.
Nutr Cancer ; 71(7): 1181-1188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30958699

RESUMO

Although several studies have investigated the cytotoxic effects of different Dianthus species, there has been only limited research into the cytotoxic effect of Dianthus carmelitarum. The purpose of this research was to evaluate the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer (WiDr) cells and the possible mechanisms involved. Total polyphenolic contents (TPC) and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography (RP-HPLC), respectively. The cytotoxic activity of the extract was determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 784.8 ± 40.3 mg gallic acid equivalent per 100 g sample, and sinapic acid and benzoic acid were detected as major phenolics in the extract. D. carmelitarum extract exhibited a selective cytotoxic effect (3.6-fold) on WiDr cells compared to normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. Phytomedical and nutraceutical applications of D. carmelitarum may represent promising approaches in the treatment of cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Dianthus/química , Extratos Vegetais/farmacologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Dimetil Sulfóxido/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/análise
3.
Gynecol Endocrinol ; 35(4): 301-304, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30600729

RESUMO

OBJECTIVE: To compare the effects of alitretionin and isotretionin on endometrial peritoneal implants and serum vascular endothelial growth factor (VEGF) levels. STUDY DESIGN: Forty-eight female Sprague Dawley rats were used. Initially surgical rat endometriosis model was done. The endometrial implant volume was measured and rats were randomly divided into four groups. Group 1: Control group (rats did not get any drug but having endometriotic implants), group 2: rats receiving po isotretionin 10 mg/kg per day for 10 d, group 3: rats receiving po isotretionin 20 mg/kg per day for 10 d and group 4: rats receiving po alitretionin 80 mg/kg per day for 10 d. After 1-week medication, rats were sacrificed and size, histopathology of endometriotic implant and levels of VEGF were evaluated. RESULTS: Volumes of peritoneal endometrial implants were significantly decreased in Group 2 and Group 3 compared with initial values. However, there were no significant changes in histopathological scores and serum VEGF levels in all groups. CONCLUSIONS: This study finding may suggest the possible medical treatment modality of isotretionin on endometriosis. However, alitretionin (potent retinoid) does not have potent regressive effect on endometriotic implants as in isotretionin.


Assuntos
Alitretinoína/uso terapêutico , Endometriose/tratamento farmacológico , Isotretinoína/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangue , Alitretinoína/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Isotretinoína/farmacologia , Ratos Sprague-Dawley
4.
Saudi Pharm J ; 25(2): 241-248, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28344475

RESUMO

Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM) and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3) cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC), ferric reducing antioxidant power (FRAP) and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

5.
Nutr Cancer ; 69(1): 74-83, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27880042

RESUMO

Many studies have reported cytotoxic effects of different Morus species, but there have been only limited studies on the cytotoxic effect of Morus rubra. The aims of this study were to evaluate the cytotoxic effect of dimethyl sulfoxide extract of M. rubra and to investigate, for the first time, its probable cytotoxic activity in human colon cancer (WiDr) cells, together with the mechanism involved. The cytotoxic activity of extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of extract was then evaluated in terms of apoptosis, and the cell cycle using flow cytometry, mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase and C/EBP homologous protein (CHOP) were investigated using reverse-transcription PCR (RT-PCR). M. rubra extract exhibited moderate selective cytotoxicity on colon cancer cells compared with fibroblast cells. Extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP in WiDr cells. Additionally, M. rubra extract significantly repressed telomerase and induced CHOP expressions in WiDr cells. Our results demonstrate that targeting telomerase and endoplasmic reticulum stress represents a promising strategy in colon cancer therapy, and M. rubra may have considerable potential for development as a novel natural product-based anticancer agent.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Morus/química , Extratos Vegetais/farmacologia , Telomerase/genética , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fator de Transcrição CHOP/genética
6.
J Pediatr Gastroenterol Nutr ; 58(5): 654-60, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24787093

RESUMO

OBJECTIVES: The aim of the study was to assess seasonal prevalence of vitamin D deficiency according to sex and to determine the relations between serum levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) and sociodemographic characteristics in otherwise healthy schoolchildren during spring and autumn. METHODS: In a cross-sectional study, 746 healthy students aged between 11 and 18 years were recruited during spring (n = 375) and autumn (n = 371). Sociodemographic data were collected by a questionnaire. Serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase were measured. Serum 25(OH)D levels were categorized as <50 nmol/L (vitamin D deficiency) and <25 nmol/L (severe deficiency). RESULTS: Mean ± standard deviation 25(OH)D levels were 22.3 ± 10.5 nmol/L in girls and 28.5 ± 17.0 nmol/L in boys during spring (P < 0.001) and 36.5 ± 20.3 nmol/L in girls and 45.0 ± 18.5 nmol/L in boys during autumn (P < 0.001). The prevalence of vitamin D deficiency was 93% during spring and 71% during autumn. There was a negative correlation between 25(OH)D and PTH levels (P < 0.01). We determined a cutoff point of serum 25(OH)D in which the mean serum PTH concentration began to increase as 35.8 nmol/L (P < 0.0001). The age, sex, and calcium level were found to be independent predictors for vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent among healthy schoolchildren. It is noteworthy that 25(OH)D levels were significantly lower in girls and during autumn. We recommend vitamin D supplementation for children in addition to more time spent for outdoor activities for sensible sunlight exposure.


Assuntos
Hormônio Paratireóideo/sangue , Estações do Ano , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Criança , Estudos Transversais , Suplementos Nutricionais , Exercício Físico , Feminino , Humanos , Masculino , Fatores Sexuais , Luz Solar , Inquéritos e Questionários , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/prevenção & controle
7.
Endocrine ; 47(1): 290-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24415172

RESUMO

The aim of this study was to determine the prevalence of goiter and related risk factors in an adult population in a formerly iodine-deficient area of Turkey. In this cross-sectional study, we enrolled 2,500 subjects (1,270 women and 1,230 men, aged over 20 years) by multistage sampling. Blood and urine specimens were collected for the assessment of thyroid function. Thyroid ultrasonography (USG) was performed to measure thyroid volume and evaluate nodules. The overall goiter prevalence was 26.5 % (28.4 % in women, 24.5 % in men, P < 0.05). Median thyroid volume was 15.59 mL (13.65 mL in women, 17.96 mL in men, P < 0.0001). Median urinary iodine was 122.79 µg/L. USG revealed thyroid nodules in 35.2 % of the subjects (38.4 % in women, 31.8 % in men, P < 0.005). Age group analysis revealed the lowest rate in the 20-29-year age group (12.5 %), which increased with age, reaching the highest level (38.4 %) in the 70+ years age group. The prevalence of goiter was negatively correlated with education level and positively correlated with body mass index (BMI) and positive family history. According to occupation, goiter prevalence was highest in farmers (35.3 %) and housewives (32.2 %). Despite a normal range of current urinary iodine excretion levels, prevalence of goiter in this adult population in a formerly iodine-deficient province of Turkey remained high, even about 10 years after salt iodine supplementation program introduction. In addition, the goiter prevalence was higher for female gender, advanced age, positive family history of goiter, low education level, and high BMI.


Assuntos
Bócio/epidemiologia , Bócio/etiologia , Iodo/deficiência , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Bócio/diagnóstico por imagem , Bócio/prevenção & controle , Humanos , Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Cloreto de Sódio na Dieta/uso terapêutico , Turquia/epidemiologia , Ultrassonografia , Adulto Jovem
8.
J Endod ; 33(5): 570-3, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17437874

RESUMO

Propolis is a multifunctional material used by bees in the construction and maintenance of their hives. Propolis possesses several biologic activities such as anti-inflammatory, antibacterial, antioxidant, antifungal, antiviral, and tissue regenerative, among others. The purpose of this study was to determine the ability of propolis to serve as a temporary storage medium for the maintenance of periodontal ligament (PDL) cell viability of avulsed teeth. PDL cells were obtained from healthy third molars and cultured in Dulbecco's Modified Eagles Medium (DMEM). Cultures were subjected to 10% propolis solution, 20% propolis solution, long-shelf life light milk with lower fat content (milk), Hank's Balanced Salt Solution, tap water as the negative control, and DMEM as the positive control. Tissue culture plates were incubated with experimental media at 37 degrees C for 1, 3, 6, 12, or 24 hours. PDL cell viability was assessed by trypan blue exclusion. Statistical analysis of the data was accomplished by using one-way analysis of variance complemented by the Tukey test. The level of significance was 5% (p<0.05). The results showed that 10% propolis was a more effective storage medium than other groups. In conclusion, propolis can be recommended as a suitable transport medium for avulsed teeth.


Assuntos
Soluções para Preservação de Órgãos/uso terapêutico , Ligamento Periodontal/efeitos dos fármacos , Própole/uso terapêutico , Preservação de Tecido/métodos , Análise de Variância , Animais , Sobrevivência Celular/efeitos dos fármacos , Humanos , Soluções Isotônicas/uso terapêutico , Leite , Ligamento Periodontal/citologia , Avulsão Dentária/terapia
9.
Endocrine ; 30(2): 175-83, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17322576

RESUMO

OBJECTIVE: Graves' disease is an organ-specific autoimmune disease with unknown etiology. TSHR Ab plays the most important role for the pathogenesis of Graves' disease. Recently, the role of cytokines for the pathogenesis of Graves' disease has been studied extensively. Royal jelly (RJ) is a creamy product secreted by young nurse worker bees (Apis mellifera), and it is synthesized in the hypopharyngeal and mandibular glands. RJ has been reported to have such pharmacological characteristics as antitumor, antibacterial, antihypercholesterolemic, antiallergic, antiinflammatory, and immunomodulatory properties. The major aim of the present study is to evaluate the effect of RJ on autoimmunity in peripheral lymphocyte culture and to establish the therapeutic doses. RESEARCH DESIGN AND METHODS: In the first phase, lymphocyte cell isolation from four voluntary healthy subjects was performed to find the effective concentration of RJ on immunity. Serial dilutions of the RJ were prepared (0-5 mg/mL). All isolated lymphocyte cells were treated with the above diluted samples. MTT test was carried out after incubation of 72 h. In the second phase, six patients with Graves' disease, newly diagnosed by clinical and laboratory methods and admitted to my hospital and untreated were identified. RJ samples of 0 and 4 mg/mL were incubated in a culture medium for 72 h with isolated lymphocytes obtained from the patients. After incubation, MTT test in lymphocyte cell culture, Th1 cytokines IFN-gamma, TNF-alpha, and IL-12, and Th2 cytokines IL-4 and IL-10 levels by the enzyme amplified sensitivity immunoassay (EASIA) method and TSHR Ab by the radioreceptor method were determined. RESULTS: The concentration causing lymphocytes to proliferate was found to be 4 mg/mL by MTT test after incubation of 72 h in cell culture medium. Of the cytokines produced and secreted from lymphocytes, IFN-gamma increased, whereas, other cytokines decreased in RJ concentration of 4 mg/mL. Significant differences were found only for IFN-gamma and TNF-alpha. IL-4 concentrations were kept near the level of significancy. Of Th1/Th2 ratios, IFN-gamma/IL-4 and IFN-gamma/IL-10 ratios also exhibited significant differences between 0 and 4 mg/mL. RJ treatment in lymphocytes from patients with Graves' disease shifted the Th1/Th2 cytokine ratio to the side of Th1 cytokine. Therefore, RJ using the treatment and establishing a remission of Graves' disease may be effective as an antithyroid drug treatment. TSHR Ab levels of lymphocyte cell culture supernatants treated with RJ showed significant decreases. Also, the result may suggest that RJ may exert an effect similar to an antithyroid drug for decreasing TSHR Ab levels. CONCLUSIONS: RJ may be effective as an immunomodulatory agent in Graves' disease.


Assuntos
Autoimunidade/efeitos dos fármacos , Ácidos Graxos/uso terapêutico , Doença de Graves/tratamento farmacológico , Doença de Graves/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Adulto , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Doença de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade
10.
Int Immunopharmacol ; 5(11): 1652-7, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16039555

RESUMO

Bee-collected pollen and propolis are apicultural products which are composed of nutritionally valuable substances and contain considerable amounts of polyphenol substances which may act as potent antioxidants. We wanted to show if respiratory burst within a cancer cell lines could be influenced when incubated with pollen and propolis extracts or not. Pollen and propolis extracts at concentrations of 50, 25, 12.5 and 0 mg/ml were prepared by dimethyl sulfoxide (DMSO). K-562 cell cultures and mononuclear cell (MNC) cultures prepared from a peripheral blood sample to serve as control cells were incubated with extracts for 24 h. Determination of respiratory burst was carried out by intracellular dichlorofluorescein (DCFH) test by using flow-cytometric fluorescence analysis. While about 90% and 66% fluorescence was detected at zero concentrations for both K-562 and MNC cultures, fluorescence positivity decreased (between 3.8% and 11.8%) as concentrations of both propolis and pollen extracts increased for K-562 cell culture, but unchanged (between 20% and 83%) for MNC culture. It was concluded that pollen and propolis extracts inhibit respiratory burst within cancer cell lines probably by their antioxidant potentials.


Assuntos
Pólen , Própole/farmacologia , Explosão Respiratória/efeitos dos fármacos , Células Cultivadas , Misturas Complexas/farmacologia , Humanos , Células K562 , Leucócitos Mononucleares/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Turquia
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