Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Phytomedicine ; 80: 153380, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33091856

RESUMO

BACKGROUND: Current treatments for overactive bladder (OAB) have limited efficacy, low persistence and a high rate of adverse events commonly leading to treatment cessation in clinical practice. Clinicians in Asia commonly use traditional Chinese medicine as an alternative for OAB treatment despite it having uncertain efficacy and safety. To evaluate the efficacy and safety of cinnamon patch (CP) treatment for alleviating symptoms of OAB, a double-blind randomized, placebo-controlled trial was conducted in the present study. MATERIALS AND METHODS: In this 6-week randomized clinical trial conducted in an outpatient setting, 66 subjects diagnosed as having OAB were enrolled and treated with a placebo (n=33) or CP (n=33). The OAB symptom score (OABSS) was selected as the primary end point, and a patient perception of bladder condition (PPBC), an urgency severity scale (USS), and post-voiding residual urine (PVR) volume were selected as secondary end points. Statistical analyses were performed with IBM SPSS Statistics 20. Groups were compared using an independent sample t-test, Fisher exact test, and Chi-squared test. RESULTS: In total, 66 participants (40 women and 26 men), 60.35 ± 12.77 years of age, were included in the intention-to-treat analyses. Baseline characteristics were comparable between the CP (n ==33) and placebo (n ==33) groups. Treatment with a CP showed statistically significant differences in reductions in OABSS scores (9.70 ± 2.20 to 6.33 ± 2.42), PPBC scores (3.36 ± 0.60 to 2.15 ± 0.83), and USS scores (2.67 ± 0.54 to 1.64 ± 0.60). CONCLUSIONS: Compared to a placebo, treatment with CP might be considered an effective and safe complementary therapy for OAB. Further studies employing a positive control, different dosage forms, larger sample sizes, and longer treatment periods are warranted.

2.
J Ethnopharmacol ; 264: 113126, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32763416

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is a major bone health issue worldwide. There is an unmet medical need for osteoporosis treatments, a disease which disproportionately impacts women. Exploring botanicals to prevent or treat osteoporosis is currently an interest of investigations. Rhizomes of Davallia mariesii T. Moore ex Baker (Davalliacea) are used an indigenous herbal medicine in Asia for injuries due to fractures, contusions, and strains. AIM OF THE STUDY: In the present study, we investigated the osteogenic effect of the water extract of rhizomes of D. mariesii (DMH) on bone loss induced by an ovariectomy (OVX) in mice and also its impact on osteogenesis in primary human osteoblasts (HObs). Additionally, we performed a quantitative analysis of compounds in the DMH extract. MATERIALS AND METHODS: OVX C57BL/6J mice were orally administrated DMH extract for 12 weeks, and microarchitecture parameters were examined by microcomputed tomography. DMH extract was fractionated in a bio-guided manner, and fractions were isolated to obtain active compounds using HObs. Cell viability was evaluated by an MTT assay. Characteristics of early and late osteogenesis were analyzed by alkaline phosphatase activity and a mineralization assay. Molecular mechanisms were explored by a real-time quantitative PCR. Compounds in the DMH extract were identified and quantified using liquid chromatography tandem mass spectroscopy (LC-MS/MS). RESULTS: DMH improved bone mineral densities of vertebrae and the femur. Through microarchitectural observations, DMH significantly decreased the bone surface/volume ratio and trabecular separation, and also increased the connectivity density in the OVX group. Additionally, DMH inhibited osteoclast differentiation in receptor activator of nuclear factor-κB ligand-induced osteoclasts and increased bone formation in HObs. After bio-guided fractionation and isolation, we found that eriodictyol-7-O-ß-d-glucuronide (2) significantly increased alkaline phosphatase activity, and 5-O-ß-d-(6-O-vanilloylglucopyranosyl)gentisic acid (3) substantially enhanced mineral deposition. In HObs, compound 3 was more potent in upregulating expressions of bone morphogenetic protein-2, bone sialoprotein, osteopontin, osterix, and estrogen receptor-α. The amount of bioactive compound 3 in DMH was 5.68 ±â€¯0.64 mg/g of dry weight according to LC-MS/MS. CONCLUSION: For the first time we report that D. mariesii and its isolated compounds demonstrated potent osteogenic activities. Quantitative results of D. mariesii could be a reference for phytochemical analyses.

3.
Food Funct ; 11(6): 5420-5431, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32475999

RESUMO

Osteogenesis plays a vital role in the maintenance of bone health. Imbalances in osteogenesis influence the onset of several bone loss-associated diseases. The intake of Uraria crinita (Fabaceae) through dietary supplements is advised for childhood bone dysplasia. This botanical provides edible tonics and detoxifiers, and is also used as a folk beverage. We evaluated the osteogenic effects of a 50% ethanol extract of the root of U. crinita on primary human osteoblasts (HObs) and initiated a novel comprehensive phytochemical strategy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quality control of this functional food. Two isoflavones, genistein (5) and 5,7-dihydroxy-3',5'-dihydroxyisoflavone (6), increased the alkaline phosphatase activity (differentiation stage); the flavone glycoside vitexin (1), and the phenolic acid salicylic acid (2) enhanced the mineralization (mature stage). The isoflavone 2'-hydroxygenistein (4) possessed high osteogenic potential among the isolated compounds in HObs. It promoted osteogenesis-related stages and upregulated the gene expressions in a dose-dependent manner. The major compounds in the active fraction were quantitatively analyzed via phytochemical fingerprint detection. These LC-MS/MS-based phytochemical perspectives can act as reference standards in developing food supplements from U. crinita.

4.
J Food Drug Anal ; 28(1): 147-158, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883603

RESUMO

The incidence of neurodegeneration leading to the conditions such as Alzheimer's and Parkinson's diseases are on the increase, they require the approaches that focus on protection prevention rather than treatment. Plants are rich sources of many compounds which possess medicinal properties. We sought to investigate the neuroprotective effects of Uncariahirsuta and its compounds on d-galactose-induced stress in BALB/c mice as well as 6-hydroxydopamine (6-OHDA)-induced stress in mouse nerve growth factor (mNGF)-differentiated PC12 cells. Our results demonstrate that the 95% ethanol extract of U. hirsuta reversed the d-galactose-induced learning and memory dysfunctions and decreased the malodialdehyde levels. Furthermore, the isolated compounds, 5ß-carboxystrictosidine (1) and chlorogenic acid (2), protected mNGF-differentiated PC12 cells against toxicity induced by 6-OHDA by acting as antiapoptotic agents. The 50% inhibitory concentration (IC50) for intracellular reactive oxygen species (ROS) scavenging was found to be 24.5 (for 1) and 19.7 µM (for 2), and both 1 and 2 reduced intracellular calcium levels with respective IC50 values of 46.9 and 27 µM. Interestingly, both compounds inhibited caspase 3 and 9 activities with respective IC50 values of 25.6 and 24.5 µM for 1 and 19.4 and 16.3 µM for 2. Our results identify U. hirsuta and its active compounds as potential neuroprotective agents and deserve further evaluation for drug development for neuroprotection in the future.

5.
Int J Mol Sci ; 20(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31247918

RESUMO

Bone metabolism is a homeostatic process, imbalance in which leads to the onset of diseases such as osteoporosis and osteopenia. Although several drugs are currently available to treat such conditions, they are associated with severe side effects and do not enhance bone formation. Thus, identifying alternative treatment strategies that focus on enhancing bone formation is essential. Herein, we explored the osteogenic potential of Turpinia formosana Nakai using human osteoblast (HOb) cells. The plant extract was subjected to various chromatographic techniques to obtain six compounds, including one new compound: 3,3'-di-O-methylellagic acid-4-O-α-l-arabinofuranoside (1). Compounds 3,3'-di-O-methylellagic acid-4-O-α-l-arabinofuranoside (1), gentisic acid 5-O-ß-d-(6'-O-galloyl) glucopyranoside (2), strictinin (3), and (-)-epicatechin-3-O-ß-d-allopyranoside (6) displayed no significant cytotoxicity toward HOb cells, and thus their effects on various osteogenic markers were analyzed. Results showed that 1-3 and 6 significantly increased alkaline phosphatase (ALP) activity up to 120.0, 121.3, 116.4, and 125.1%, respectively. Furthermore, 1, 2, and 6 also markedly enhanced the mineralization process with respective values of up to 136.4, 118.9, and 134.6%. In addition, the new compound, 1, significantly increased expression levels of estrogen receptor-α (133.4%) and osteogenesis-related genes of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), bone morphogenetic protein (BMP)-2, bone sialoprotein (BSP), type I collagen (Col-1), and brain-derived neurotropic factor (BDNF) by at least 1.5-fold. Our results demonstrated that compounds isolated from T. formosana possess robust osteogenic potential, with the new compound, 1, also exhibiting the potential to enhance the bone formation process. We suggest that T. formosana and its isolated active compounds deserve further evaluation for development as anti-osteoporotic agents.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Traqueófitas/química , Biomarcadores , Expressão Gênica , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo
6.
Cancers (Basel) ; 11(3)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818855

RESUMO

Colorectal cancer (CRC) is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Because of the use of first-line CRC treatments, such as irinotecan (IRI), is hindered by dose-limiting side effects, improved drug delivery systems may have major clinical benefits for CRC treatment. In this study, we generate and characterize liposomal irinotecan (Lipo-IRI), a lipid-based nanoparticle, which shows excellent bioavailability and pharmacokinetics. Additionally, this formulation allows IRI to be maintained in active form and prolongs its half-life in circulation compared to IRI in solution. Compared with IRI statistically, the level of prostaglandin E2 (PGE2) in colonic tissue decreases, and Bifidobacterium spp. (beneficial intestinal microbiota) content increases in the Lipo-IRI-treated group. Moreover, no damage is observed by the hematoxylin and eosin staining of the normal tissue samples from the Lipo-IRI-treated group. In a xenograft mouse model, CRC tumors shrink markedly following Lipo-IRI treatment, and mice receiving a targeted combination of Lipo-IRI and liposomal doxorubicin (Lipo-Dox) extend their survival rate significantly. Overall, our results demonstrate that this formulation of Lipo-IRI shows a great potential for the treatment of colorectal cancer.

7.
J Photochem Photobiol B ; 175: 244-253, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28917186

RESUMO

Ultraviolet (UV) irradiation leads to skin photoaging because of the upregulation of matrix metalloproteinase (MMP)-1 and downregulation of type I collagen and tissue inhibitor of metalloproteinase (TIMP)-1. Eriobotrya deflexa (Hemsl.) Nakai (Rosaceae) is a flowering plant endemic to Taiwan, and its leaves have been used as an expectorant and in antitussive folk remedy. Our previous studies have demonstrated that an E. deflexa leaf extract functions as a free radical scavenger. The current evaluated the antiphotoaging effect of partitioned fractions and specific compounds from the leaves of E. deflexa by using bioguided isolation, compound identification, and biological activity testing with UVB-irradiated human fibroblasts (WS-1 cells). E. deflexa leaves were extracted with 95% ethanol and then partitioned using a sequential treatment of n-hexane, ethyl acetate, and n-butanol (n-BuOH). The bioactive n-BuOH fraction was used for isolation and purification through chromatography. The compounds were identified by analyzing their physical and spectroscopic properties. We identified eight compounds from this fraction; of these compounds, 3-O-α-l-rhamnopyranosyl-(1‴→6″)-ß-d-galactopyranoside (1), hyperin (2), afzelin (5), and cryptochlorogenic acid methyl ester (7) were isolated from E. deflexa for the first time, and they exhibited MMP-1 inhibition activity. The IC50 values were 96.5, 89.5, 93.4, and 92.8µM for 1, 2, 5, and 7, respectively. These compounds also enhanced the expression of procollagen type I, and TIMP-1 and hyperin (2) were found to be most effective with IC50 values of 56.7 and 70.3µM, respectively. Hyperin (2) could reduce intracellular reactive oxygen species production in UVB-irradiated WS-1 cells, with the corresponding IC50 value being 80.7µM. Liquid chromatography triple-quadrupole mass spectrometry was used for the quantitative and chemical fingerprint analysis of active compounds. Quercetin 3-O-α-l-rhamnopyranosyl-(1‴→6″)-ß-d-galactopyranoside (1), hyperin (2), afzelin (5), and cryptochlorogenic acid methyl ester (7) constituted 24.2±3.9, 5.5±1.0, 3.4±0.3, and 67.1±8.1mg/g of dry weight in the active n-BuOH fraction, respectively. Our results demonstrate that the extract and the isolated active compounds from E. deflexa leaves possess the potential for protection against skin photoaging.


Assuntos
Senescência Celular/efeitos dos fármacos , Eriobotrya/química , Extratos Vegetais/química , Substâncias Protetoras/química , Raios Ultravioleta , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Senescência Celular/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Colágeno Tipo I/análise , Ensaio de Imunoadsorção Enzimática , Eriobotrya/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Metaloproteinase 1 da Matriz/análise , Extratos Vegetais/análise , Folhas de Planta/química , Folhas de Planta/metabolismo , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Espectrometria de Massas em Tandem
8.
Oncol Rep ; 35(2): 659-68, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26719057

RESUMO

The fact that many chemotherapeutic drugs cause chemoresistance and side effects during the course of colorectal cancer treatment necessitates development of novel cytotoxic agents aiming to attenuate new molecular targets. Here, we show that Astragalus membranaceus (Fischer) Bge. var. mongolicus (Bge.) Hsiao (AM), a traditional Chinese medicine, can inhibit tumor growth in vivo and elucidate the underlying molecular mechanisms. The antitumor effect of AM was assessed on the subcutaneous tumors of human colorectal cancer cell line HCT116 grafted into nude mice. The mice were treated with either water or 500 mg/kg AM once per day, before being sacrificed for extraction of tumors, which were then subjected to microarray expression profiling. The gene expression of the extraction was then profiled using microarray analysis. The identified genes differentially expressed between treated mice and controls reveal that administration of AM suppresses chromosome organization, histone modification, and regulation of macromolecule metabolic process. A separate analysis focused on differentially expressed microRNAs revealing involvement of macromolecule metabolism, and intracellular transport, as well as several cancer signaling pathways. For validation, the input of the identified genes to The Library of Integrated Network-based Cellular Signatures led to many chemopreventive agents of natural origin that produce similar gene expression profiles to that of AM. The demonstrated effectiveness of AM suggests a potential therapeutic drug for colorectal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/farmacologia , Transcriptoma/efeitos dos fármacos , Animais , Astragalus propinquus , Células HCT116 , Humanos , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Int J Mol Sci ; 16(12): 28598-613, 2015 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-26633381

RESUMO

Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata) Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9) and 3,4-dihydroxy-5-methoxybiphenyl-2'-O-ß-d-glucopyranoside (13), as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate l-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver-Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics.


Assuntos
Clareadores/química , Clareadores/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pyracantha/química , Clareadores/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Células Epidérmicas , Epiderme/efeitos dos fármacos , Humanos , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/isolamento & purificação , Taiwan
10.
ACS Chem Neurosci ; 6(5): 716-24, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25692332

RESUMO

Lovastatin, a secondary metabolite isolated from Monascus-fermented red rice mold, has neuroprotective activity and permeates the blood-brain barrier. The aim of this study was to enhance the activity of lovastatin for potential use as a treatment for neuronal degeneration in Parkinson's disease. Six lovastatin-derived compounds were semisynthesized and screened for neurocytoprotective activity against 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma PC12 cells. Four compounds, designated as 3a, 3d, 3e, and 3f, significantly enhanced cell viability. In particular, compound 3f showed excellent neurocytoprotective activity (97.0 ± 2.7%). Annexin V-FITC and propidium iodide double staining and 4',6-diamidino-2-phenylindole staining indicated that compound 3f reduced 6-OHDA-induced apoptosis in PC12 cells. Compound 3f also reduced caspase-3, -8, and -9 activities, and intracellular calcium concentrations elevated by 6-OHDA in a concentration-dependent manner, without inhibiting reactive oxygen species generation. JC-1 staining indicated that compound 3f also stabilized mitochondrial membrane potential. Thus, compound 3f may be used as a neurocytoprotective agent. Future studies should investigate its potential application as a treatment for Parkinson's disease.


Assuntos
Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lovastatina/análogos & derivados , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Diferenciação Celular , Modelos Biológicos , Monascus , Fator de Crescimento Neural , Oryza , Oxidopamina , Células PC12 , Transtornos Parkinsonianos , Ratos
11.
Environ Toxicol ; 30(2): 129-36, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23765435

RESUMO

Divalent lead ions (Pb(2+) ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb(2+) from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb(2+) affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 µM lead nitrate. We found that Pb(2+) induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb(2+) . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb(2+) -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb(2+) also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb(2+) on gastrin gene activity in cell culture.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gastrinas/biossíntese , Gastrinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Chumbo/toxicidade , Fator de Transcrição AP-1/efeitos dos fármacos , Linhagem Celular Tumoral , Repressão Epigenética/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases , Fosforilação , Proteínas Proto-Oncogênicas c-jun/farmacologia
12.
J Agric Food Chem ; 62(24): 5581-8, 2014 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-24785825

RESUMO

Uraria crinita is an edible herb used as a natural food for childhood skeletal dysplasia. Ethyl acetate, n-butanol, and aqueous fractions of a 95% ethanol crude extract of U. crinita were obtained and the active ingredients isolated and purified using a bioguided method. In this manner, we isolated and identified a new active flavone glycoside, apigenin 6-C-ß-d-apiofuranosyl(1→2)-α-d-xylopyranoside (3) and 10 known components with stimulatory activity on human osteoblast cells. The new compound 3 at 100 µM significantly increased alkaline phosphatase activity (114.10 ± 4.41%), mineralization (150.10 ± 0.80%), as well as osteopontin (1.39 ± 0.01-fold), bone morphogenetic protein-2 (BMP-2, 1.30 ± 0.04-fold), and runt-related transcription factor 2 (Runx2, 1.43 ± 0.10-fold) mRNA expression through the activation of the BMP-2/Runx2 pathway. Two other components, dalbergioidin (1) and byzantionoside B (9), displayed similar effects. These results show that U. crinita and its active compounds may have the potential to stimulate bone formation and regeneration.


Assuntos
Fabaceae/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos/metabolismo , Raízes de Plantas/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Molecules ; 18(6): 6584-96, 2013 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-23736792

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF)-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration.


Assuntos
Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Indometacina/farmacologia , Neoplasias/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Sinalização do Cálcio , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indometacina/química , Neoplasias/genética , Fosforilação/efeitos dos fármacos
14.
Bot Stud ; 54(1): 51, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28510887

RESUMO

BACKGROUND: An optimized method for indirect shoot organogenesis from the leaf explants of Hygrophila pogonocalyx, a rare and endemic species in Taiwan, was developed to supply enough quantity of plant materials for the first chemical and pharmacological investigation. RESULTS: Incubation of the young leaves on Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (0.5 mg/l) and indole-3-acetic acid (0.1 mg/l) resulted in the best multiplication rate for organogenesis. The average number of adventitious buds per leaf was 22.8 ± 1.9 after 8-week culture. The adventitious buds rooted and developed into plantlets when cultured simply on MS medium. Using this protocol, up to 37,600 plants were produced from a single leaf explant in one year. From the ethanol extract of the leaves of this micropropagated plant, 13 compounds were isolated and identified, including two flavones (1, 11), four flavonols (9, 10, 12, and 13), three phenylethanoid glycosides (6-8), two alkylated glycosides (2-3), and two steroids (4-5). Of these, acteoside (7) exhibited anti-tyrosinase activity in human epidermal melanocytes and luteolin 7-O-ß-D-glucopyranoside (11) exhibited the greatest neurocytoprotective activity. CONCLUSIONS: The method, indirect shoot organogenesis from leaf explants of H. pogonocalyx, could be developed to supply enough quantity of plant materials for the chemical and pharmacological investigation. In the present study, the isolated active compounds may develop for whitening agents or treating neurodegenerative diseases in the future.

15.
Phytochemistry ; 84: 102-15, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22954731

RESUMO

The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely used to generate an experimental model of Parkinson's disease. This model is crucial in the search for compounds that diminish 6-OHDA-induced nerve growth factor (NGF)-differentiated PC12 cell death. Nephrocizin (luteolin-7-O-ß-D-glucopyranoside), a flavone glycoside, was isolated from widely distributed plants. The protective effects of pre-treatment with nephrocizin on the induced neurotoxicity in PC12 cells by 6-OHDA and its oxidative products, H2O2-, and p-quinone, were evaluated herein. Nephrocizin promoted cell viability, scavenged ROS-related products, increased cellular glutathione (GSH) levels, and reduced caspase-3 and -8 activities in 6-OHDA-, H2O2-, or p-quinone-treated PC12 cells. Furthermore, nephrocizin-conjugated metabolites in PC12 cells were identified with the boronate-affinity method and LC-MS technology, and preferential regioselectivity at the C2' and C5' positions by the nephrocizin-GSH (or NAC) adduct method was observed. These lines of evidence established that nephrocizin could form a dimer to diminish the intracellular ROS. These results demonstrate the first neuroprotective mechanism of nephrocizin against 6-OHDA-, H2O2- or p-quinone-induced cytotoxicity in PC12 cells via chemical and biological studies. These dietary antioxidants are potential candidates for use in intervention in neurodegenerative diseases.


Assuntos
Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxidopamina/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Luteolina/química , Luteolina/isolamento & purificação , Luteolina/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Oxidopamina/análogos & derivados , Células PC12 , Ratos , Relação Estrutura-Atividade
16.
Int J Mol Sci ; 13(5): 6073-88, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22754350

RESUMO

Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-d-glucoside (3), methyl 6-O-galloyl-ß-d-glucoside (4), methyl 3,6-di-O-galloyl-α-d-glucopyranoside (5), gentisic acid 5-O-α-d-(6'-O-galloyl)glucopyranoside (6), guaiacylglycerol 4-O-ß-d-(6'-O-galloyl)glucopyranoside (7), 3-methoxy-4-hydroxyphenol 1-O-ß-d-(6'-O-galloyl) glucopyranoside (8), (+)-gallocatechin (9), (+)-catechin (10), (+)-gallocatechin 3-O-gallate (11), myricetin 3-rhamnoside (12), and ampelopsin (13). All isolated compounds were tested for their antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and peroxynitrite radicals scavenging assays. Among those compounds, 11, 12, and 2 exhibited the best DPPH-, hydroxyl-, and peroxynitrite radical-scavenging activities, respectively. Compound 7 is a new compound, and possesses better scavenging activities towards DPPH but has equivalent hydroxyl radical scavenging activity when compared to BHT. The paper is the first report on free radical scavenging properties of components of the fresh pods of Caesalpinia pulcherrima. The results obtained from the current study indicate that the free radical scavenging property of fresh pods of Caesalpinia pulcherrima may be one of the mechanisms by which this herbal medicine is effective in several free radical mediated diseases.


Assuntos
Antioxidantes/química , Caesalpinia/química , Depuradores de Radicais Livres/química , Polifenóis/química , Compostos de Bifenilo/química , Catequina/química , Cromatografia/métodos , Ácido Gálico/química , Glucosídeos/química , Picratos/química , Extratos Vegetais/química
17.
Molecules ; 16(11): 9451-66, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-22075574

RESUMO

A new biflavonol glycoside, quercetin-3-O-ß-D-glucopyranoside-(3'→O-3''')-quercetin-3-O-ß-D-galactopyranoside (9), together with eight known compounds was isolated for the first time from the leaves of Machilus zuihoensis Hayata (Lauraceae). The structure of compound 9 was elucidated by various types of spectroscopic data analysis. Analysis of the biological activity assay found that compound 9 showed significant superoxide anion scavenging activity (IC50 is 30.4 µM) and markedly suppressed LPS-induced high mobility group box 1 (HMGB-1) protein secretion in RAW264.7 cells. In addition, the HMGB-1 protein secretion was also inhibited by quercitrin (3), ethyl caffeate (6), and ethyl 3-O-caffeoylquinate (7) treatment. In the LPS-stimulated inducible nitric oxide synthase (iNOS) activation analysis, two known compounds, quercetin (1) and ethyl caffeate (6), were found to markedly suppress nitric oxide (NO) production (IC50 value, 27.6 and 42.9 µM, respectively) in RAW264.7 cells. Additionally, it was determined that ethyl caffeate (6) down-regulated mRNA expressions of iNOS, IL-1ß, and IL-10 in the LPS-treatment of RAW264.7 cells via a suppressed NF-kB pathway. These results suggested for the first time that the new compound 9 and other constituents isolated from M. zuihoensis have potential anti-inflammatory and superoxide anion scavenging effects. These constituents may be useful for treating various inflammatory diseases.


Assuntos
Anti-Inflamatórios , Depuradores de Radicais Livres , Lauraceae/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Ácidos Cafeicos/farmacologia , Linhagem Celular , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Galactosídeos/química , Proteína HMGB1/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Monossacarídeos/química , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacologia , Superóxidos/química , Fator de Necrose Tumoral alfa/metabolismo
18.
PLoS One ; 6(7): e21890, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21789192

RESUMO

Haplotype association studies based on family genotype data can provide more biological information than single marker association studies. Difficulties arise, however, in the inference of haplotype phase determination and in haplotype transmission/non-transmission status. Incorporation of the uncertainty associated with haplotype inference into regression models requires special care. This task can get even more complicated when the genetic region contains a large number of haplotypes. To avoid the curse of dimensionality, we employ a clustering algorithm based on the evolutionary relationship among haplotypes and retain for regression analysis only the ancestral core haplotypes identified by it. To integrate the three sources of variation, phase ambiguity, transmission status and ancestral uncertainty, we propose an uncertainty-coding matrix which combines these three types of variability simultaneously. Next we evaluate haplotype risk with the use of such a matrix in a Bayesian conditional logistic regression model. Simulation studies and one application, a schizophrenia multiplex family study, are presented and the results are compared with those from other family based analysis tools such as FBAT. Our proposed method (Bayesian regression using uncertainty-coding matrix, BRUCM) is shown to perform better and the implementation in R is freely available.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos/genética , Modelos Genéticos , Incerteza , Teorema de Bayes , Simulação por Computador , Família , Humanos , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genética , Análise de Regressão , Fatores de Risco , Esquizofrenia/genética , Taiwan
19.
Molecules ; 16(6): 4836-49, 2011 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-21666550

RESUMO

Many diseases occur when the immune system is weakened. Intracellular signals activate immuno-responsive cells to produce cytokines that modulate the immune response. Schisandra chinensis has been used traditionally to treat general fatigue, neurasthenia, and spontaneous sweating. In the present study, the effect of constituents of S. chinensis on cytokine release by human monocytic leukemia cells (THP-1) was tested using microparticle-based flow cytometric analysis. Two major lignans, schizandrin (Sch) and gomisin A (Gom A), were identified and shown to induce interleukin (IL)-8, macrophage inflammatory protein-1ß (MIP-1ß), and granulocyte-macrophage-colony stimulating factor (GM-CSF) release by THP-1 cells. By reverse transcription polymerase chain reaction (RT-PCR) or quantitative real-time PCR, there was a dose-dependent increase of IL-8, MIP-1ß and GM-CSF mRNA levels. Thus, Sch and Gom A from S. chinensis enhance cytokine release by THP-1 cells and this effect occurs through mRNA upregulation. Upregulation of MIP-1ß and GM-CSF in particular may have clinical applications. Therefore, S. chinensis may be therapeutically beneficial by promoting humoral and cell-mediated immune responses.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Schisandra/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/química , Humanos , Fatores Imunológicos/química , Leucemia Monocítica Aguda/imunologia , Modelos Biológicos , RNA Mensageiro/metabolismo
20.
BMC Genet ; 12: 48, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21592403

RESUMO

BACKGROUND: With the completion of the international HapMap project, many studies have been conducted to investigate the association between complex diseases and haplotype variants. Such haplotype-based association studies, however, often face two difficulties; one is the large number of haplotype configurations in the chromosome region under study, and the other is the ambiguity in haplotype phase when only genotype data are observed. The latter complexity may be handled based on an EM algorithm with family data incorporated, whereas the former can be more problematic, especially when haplotypes of rare frequencies are involved. Here based on family data we propose to cluster long haplotypes of linked SNPs in a biological sense, so that the number of haplotypes can be reduced and the power of statistical tests of association can be increased. RESULTS: In this paper we employ family genotype data and combine a clustering scheme with a likelihood ratio statistic to test the association between quantitative phenotypes and haplotype variants. Haplotypes are first grouped based on their evolutionary closeness to establish a set containing core haplotypes. Then, we construct for each family the transmission and non-transmission phase in terms of these core haplotypes, taking into account simultaneously the phase ambiguity as weights. The likelihood ratio test (LRT) is next conducted with these weighted and clustered haplotypes to test for association with disease. This combination of evolution-guided haplotype clustering and weighted assignment in LRT is able, via its core-coding system, to incorporate into analysis both haplotype phase ambiguity and transmission uncertainty. Simulation studies show that this proposed procedure is more informative and powerful than three family-based association tests, FAMHAP, FBAT, and an LRT with a group consisting exclusively of rare haplotypes. CONCLUSIONS: The proposed procedure takes into account the uncertainty in phase determination and in transmission, utilizes the evolutionary information contained in haplotypes, reduces the dimension in haplotype space and the degrees of freedom in tests, and performs better in association studies. This evolution-guided clustering procedure is particularly useful for long haplotypes containing linked SNPs, and is applicable to other haplotype-based association tests. This procedure is now implemented in R and is free for download.


Assuntos
Algoritmos , Família , Estudo de Associação Genômica Ampla/métodos , Haplótipos , Análise por Conglomerados , Humanos , Funções Verossimilhança
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA