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1.
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.

2.
Biomed Pharmacother ; 133: 111037, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33249281

RESUMO

COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.

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.
Eur J Pharmacol ; 867: 172799, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31765607

RESUMO

Osteoarthritis (OA) is a common and disabling joint disease mainly characterized by cartilage degradation, with the knees most commonly affected. No effective treatment for the cartilage degradation of OA exists. Preliminary studies have revealed the protective and osteogenic effects of osthole, a natural coumarin first isolated from Cnidium monnieri (Fructus Cnidii); however, no evidence of osthole in an OA-related model has been published to date. This study further explored the effects of osthole in a monoiodoacetate (MIA)-induced OA-related animal model and focused on the molecular mechanism(s) behind the anti-inflammatory and cartilage protective effects of osthole. This study revealed that the cartilage protective effect of osthole in a MIA-induced osteoarthritis (OA) murine model can be explained by downregulation of COX-2 and RUNX2 by inhibition of NF-κB and HIF-2α up-regulated by OA induction, resulting in downregulation of MMP-13, Syndecan IV and ADAMTS-5. In addition, osthole might have anti-inflammatory and analgesic effects due to COX-2 inhibition. Osthole can be considered as a potential component of the treatment of OA, for it possesses a cartilage protective effect, as well as anti-inflammation, analgesic, and movement improving effects. Further preclinical and human clinical studies are needed to examine the efficacy and safety profile of long-term therapy.

5.
Pharmacogn Mag ; 13(52): 702-706, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200736

RESUMO

Background: Traditional Chinese herb Tithonia diversifolia, belonging to the Compositae family, has long been applied for the treatment of liver diseases. In recent years, many reports also indicated that it possesses hepato-protective, anti-inflammatory, and anti-cancer activities. Objective: In this study, we evaluated whether T. diversifolia is an effective therapy for hepatocellular carcinoma (HCC). Materials and Methods: Dry leaves of T. Diversifolia were first extracted in ethyl acetate, then further fractionated by different ratio of n-hexane-ethyl acetate (8:2→0:1) or methanol as fractions 1-6 (Td-F1 to Td-F6), respectively. We first showed that the ethyl acetate extracts of T. diversifolia leaves (Td-L-EA) exhibits growth inhibition on human hepatoma HepG2 cells. To further check the extracts-induced apoptosis, microscopic observation, fragmented chromosomal DNA electrophoresis, apoptotic DNA-detection ELISA assay, flow cytometry, and Western blot analysis were performed. Results: After isolating the effective fractions from Td-L-EA, we found strong cytotoxic effects of fraction-2 (Td-F2). By further analyzing the mechanisms of cytotoxic activities using microscopic observation, fragmented chromosomal DNA electrophoresis, apoptotic DNA-detection ELISA assay, and flow cytometry, we found that induction of apoptosis such as DNA fragmentation increased the apoptosis rate and the apoptosis sub-G1 populations in Td-F2-treated HepG2 cells. In addition, we also confirmed Td-F2-induced degradation of caspase-8, caspase-9, caspase-3, and caspase-3 substrate PARP. Besides, Td-F2 also increased the Bcl-2 proapoptotic family protein Bax expression. Conclusion: In short, our results clearly showed the induction of apoptosis by ethyl acetate extracts of T. diversifolia leaves in human hepatoma HepG2 cells, suggesting its potential application as an antitumor agent. SUMMARY: T. Diversifolia leaves were first extracted in ethyl acetate, then further fractionated by different ratio of n-hexane/ethyl acetate (8:2→0:1) or methanol.These extracts exhibit growth inhibition on human hepatoma (HCC) HepG2 cells.n-Hexane/ethyl acetate (6:4) extract (Td-F2) induces apoptosis of HCC. Abbreviations used:T. diversifolia, Tithonia diversifolia; HCC, Hepatocellular carcinoma DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethyl sulfoxide; HRP, horseradish peroxidase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; OD, optical density; SDS-PAGE, sodium dodecylsulfate-polyacrylamide gel electrophoresis; PARP, Poly (ADP-ribose) polymerase; PBS, phosphate buffered saline; PI, propidium iodide.

6.
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
7.
J Nat Prod ; 80(2): 246-253, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28169537

RESUMO

Chemical investigation of the rhizomes of Helminthostachys zeylanica led to the isolation of eight new flavonoids including six cyclized geranylflavonoids, ugonins V-X (1-3), (10R,11S)-ugonin N (4), (10R,11S)-ugonin S (5), and ugonin Y (6), as well as two quercetin glucosides, quercetin-4'-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (7) and quercetin-3-O-ß-d-glucopyranosyl-4'-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (8). The structures of these compounds were established by spectroscopic analyses and acid hydrolysis of the sugar moiety. Among the isolated compounds, 1, 2, 5, 6, ugonins J-S (9-13), ugonstilbene A (14), and ugonin L (23) were evaluated for their anti-inflammatory activity on lipopolysaccharide-induced nitric oxide (NO) production in microglial cells. Except for 1, 5, and 13, all other compounds inhibited NO production with IC50 values of 6.2-10.1 µM and were more potent than the positive control, pyrrolidine dithiocarbamate. Compounds 1, 2, 5, 6, and 10-13 were tested for antiosteoporotic activities, and ugonin K (10) exhibited the highest inhibitory activity against RANKL-induced osteoclast differentiation in RAW264.7 cells with an IC50 value of 1.8 ± 0.2 µM.


Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Gleiquênias/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Magnoliopsida/química , Osteoporose/tratamento farmacológico , Rizoma/química , Animais , Anti-Inflamatórios não Esteroides/química , Flavonoides/química , Glucosídeos/análise , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Quercetina/farmacologia , Células RAW 264.7/efeitos dos fármacos , Taiwan
8.
Molecules ; 20(7): 12314-27, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26198219

RESUMO

Calophyllum inophyllum is a coastal plant rich in natural substances. Its ingredients have been used for the development of an anti-human immunodeficiency virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the ethanol extract of the fruit was chromatographically separated using silica gel and Sephadex LH-20 columns to obtain the major compound, calophyllolide. The fruits were harvested from September to December in 2011; a quantitative analysis of the calophyllolide content was conducted using HPLC to explore the differences between the different parts of the fruit during the growing season. The results showed that in fruits of C. inophyllum, calophyllolide exists only in the nuts, and dried nuts contain approximately 2 mg·g-1 of calophyllolide. The calophyllolide levels in the nuts decreased during maturity. In addition, calophyllolide dose-dependently enhanced alkaline phosphatase (ALP) activity in murine osteoblastic MC3T3-E1 cells, without significant cytotoxicity. The expression of osteoblastic genes, ALP and osteocalcin (OCN), were increased by calophyllolide. Calophyllolide induced osteoblasts differentiation also evidenced by increasing mineralization and ALP staining.


Assuntos
Calophyllum/química , Cumarínicos/análise , Cumarínicos/farmacologia , Osteoblastos/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Calophyllum/crescimento & desenvolvimento , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Frutas/química , Expressão Gênica , Camundongos , Células NIH 3T3 , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Extratos Vegetais/farmacologia , Fator de Transcrição Sp7 , Fatores de Transcrição/metabolismo
9.
Bipolar Disord ; 17(3): 269-77, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25257835

RESUMO

OBJECTIVE: Research evidence has shown that bipolar disorder (BD) and unipolar depression (UD) are both related to inflammatory dysregulation, but few studies have compared the levels of cytokines between these two disorders. METHODS: Study subjects were age- and gender-matched outpatients with BD or UD and normal controls (NC). Severities of depression and mania symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS). Pro-inflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1), soluble p-selectin receptor (sP-selectin), and monocyte chemotactic protein-1 (MCP-1), were assessed in all subjects by enzyme-linked immunosorbent assays. RESULTS: In all, 130 patients with BD, 149 patients with UD, and 130 NC were enrolled in the study; 67.6% were female and the average age was mean ± standard deviation (SD) 43.5 ± 11.8 years. The BD group had a significantly higher smoking rate, more medical comorbidity, higher body mass index (BMI), and higher levels of sIL-2R, sIL-6R, CRP, sTNF-R1, and MCP-1 (all p < 0.01) than the UD and NC groups. When the remitted patients with BD (YMRS scores ≤ 12) were compared with the patients with UD, controlling for age, MADRS score, smoking, medical comorbidity, and BMI in the regression model, the results showed that the BD group had significantly higher levels of sIL-6R (p < 0.001), CRP (p = 0.045), sTNF-R1 (p = 0.036), and MCP-1 (p = 0.001) than the UD group. CONCLUSIONS: Higher levels of sIL-6R, CRP, sTNF-R1, and MCP-1 were noted in BD than in UD. These results may suggest a more severe inflammatory dysregulation in BD. Further studies are required to investigate whether these cytokines could be biomarkers for affective disorders.


Assuntos
Transtorno Bipolar/imunologia , Citocinas/imunologia , Transtorno Depressivo Maior/imunologia , Adulto , Biomarcadores , Índice de Massa Corporal , Proteína C-Reativa/imunologia , Estudos de Casos e Controles , Quimiocina CCL2/imunologia , Transtorno Depressivo/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/imunologia , Escalas de Graduação Psiquiátrica , Receptores de Interleucina-2/imunologia , Receptores de Interleucina-6/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia
10.
PLoS One ; 9(2): e89159, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24558484

RESUMO

We recently reported that oral administration of a (+)-vitisin A-enriched product prepared from Vitis thunbergii obviously ameliorated bone loss in ovariectomized mice and (+)-vitisin A was able to inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells. Here we further clarified the mechanism(s) by which (+)-vitisin A targets osteoclastic differentiation and activity. Osteoclast-characteristic enzyme activity was determined using gel zymography or spectroflurometric-based assay. Expression of signal molecules was analyzed via Western blot or immunoprecipitation. Results showed that (+)-vitisin A suppressed RANKL-induced multinuclear cells (MNCs) formation and bone resorption which was accompanied with reduction in ß3 integrin, osteoclast stimulatory transmembrane protein (OC-STAMP), matrix metalloproteinase-9 (MMP-9) and cathepsin K proteins expression. (+)-Vitisin A also down-regulated the proteolytic activities of MMP-9 and cathepsin K via targeting at the late stage function. (+)-Vitisin A prominently abrogated RANKL-triggered nuclear translocations of NF-κB, AP-1 (c-Fos/c-Jun dimer) and associated induction and nuclear accumulation of nuclear factor of activated T cells c1 (NFATc1). The upstream IκB degradation as well as ERK and JNK phosphorylation were also substantially repressed. Transfection with siRNA targeting tumor necrosis factor receptor associated factor 6 (TRAF6) clearly restrained RANKL-induced MNCs formation and NFATc1 induction. Interesting, RANKL triggered poly-ubiquitination of TRAF6 and associated TRAF6-TAK1 (transforming growth factor ß-activated kinase 1) complex formation was prominently attenuated by (+)-vitisin A. Furthermore, the interaction between c-src tyrosine kinase (c-Src) and ß3 was markedly induced by RANKL stimulation. (+)-Vitisin A significantly attenuated this interaction when concomitant treated with RANKL in RAW264.7 cells, but failed to affect c-Src/ß3 complex formation when post-cultured with MNCs. Taken together, (+)-vitisin A suppressed bone resorption possibly via interruption of RANKL-induced TRAF6 ubiquitination and associated downstream signaling pathways. Furthermore, action through negative regulation of the proteolytic activity of MMP-9 and cathepsin K might also contribute to the anti-resorption effect of (+)-vitisin A.


Assuntos
Benzofuranos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/fisiologia , Fenóis/farmacologia , Fator 6 Associado a Receptor de TNF/metabolismo , Ubiquitinação/efeitos dos fármacos , Análise de Variância , Animais , Western Blotting , Catepsina K/antagonistas & inibidores , Imunoprecipitação , MAP Quinase Quinase Quinases/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Camundongos , Osteoclastos/efeitos dos fármacos , Ligante RANK/antagonistas & inibidores , Espectrometria de Fluorescência
11.
J Affect Disord ; 155: 28-34, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24176538

RESUMO

BACKGROUND: More than two-thirds of depressed patients complain of somatic and pain symptoms, which are frequently regarded as a psychological reaction. Although there is a growing body of evidence showing that depression is related to immune abnormalities, few studies have investigated the association between inflammatory cytokines and somatic/pain symptoms. METHOD: Patients with depressive disorder but without any medical disorders, and age/gender/body mass index (BMI)-matched healthy subjects were enrolled. All the subjects completed the self-rating scales of the Beck Depression Inventory-II and the Depression and Somatic Symptoms Scale, which was comprised of depressive, somatic, and pain subscales. Pro-inflammatory cytokines, including C-reactive protein (CRP), interleukin-2 receptor (sIL-2R), soluble interleukin 6 receptor (sIL-6R), soluble TNF-receptors (sTNF-R), soluble P-selectin (sP-selectin), monocyte chemotactic protein-1 (MCP-1), and adiponectin, were assessed by enzyme-linked immunosorbent assays. RESULTS: In all, 109 patients with depressive disorder and 126 normal controls were enrolled. The patients with depressive disorder had significantly more severe depression, somatic and pain symptoms (all p<0.001), and higher levels of sIL-2R (p<0.0001), sTNF-R (p<0.001), and sP-selectin (p=0.005) than the normal control group. Using multivariate regression analysis with controlling of age, gender, BMI, and other pro-inflammatory cytokines, sIL-2R was the most significant predictor for depressive symptoms (p<0.0001); with further controlling of severity of depressive symptom, sP-selectin was the only predictor for somatic (p=0.002) and pain (p=0.059) symptoms. CONCLUSION: The elevated sP-selectin associated with somatic symptoms in depression, may indicate early micro-vascular changes occur subtly, and provide neurobiological evidence for somatic and pain symptom in depression.


Assuntos
Citocinas/efeitos adversos , Depressão/epidemiologia , Dor/epidemiologia , Transtornos Somatoformes/epidemiologia , Adiponectina/efeitos adversos , Adiponectina/análise , Adulto , Proteína C-Reativa/efeitos adversos , Proteína C-Reativa/análise , Estudos de Casos e Controles , Quimiocina CCL2/efeitos adversos , Quimiocina CCL2/análise , Citocinas/análise , Depressão/sangue , Depressão/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/efeitos adversos , Selectina-P/análise , Dor/sangue , Dor/imunologia , Escalas de Graduação Psiquiátrica , Receptores de Interleucina-2/análise , Receptores de Interleucina-6/análise , Receptores do Fator de Necrose Tumoral/análise , Índice de Gravidade de Doença , Transtornos Somatoformes/sangue , Transtornos Somatoformes/imunologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-23662133

RESUMO

Vitis thunbergii is used in Taiwan as a botanical supplement for inflammatory bone diseases. This study aims to examine its direct effect on bone metabolism. Three-month-old female mice were randomly divided into ovariectomized control (OVX), sham operated (SHAM), and ovariectomy treated with either 17 ß -estradiol or a special ingredient (VtR) fractionated from an ethanol extract of V. thunbergii started two weeks after ovariectomy. VtR treatment for 8 weeks significantly ameliorated the deterioration of bone mineral density and reversed all the ovariectomy-induced changes in µ -CT parameters. The antiosteoporotic effect of VtR accompanied decrease in serum levels of C-terminal telopeptides of type I collagen (CTx), interleukin-7, and ration of RANKL/osteoprotegerin (OPG) but rise in osteocalcin concentration. Sparse calcified microarchitecture and less alkaline-phosphatase- (ALP-) positive cells were observed at the femur and vertebral sites in OVX mice while VtR remarkably restored such variation. HPLC analysis showed (+)-vitisin-A, (-)-vitisin-B, and ampelopsin C predominated in VtR. Both (-)-vitisin B and ampelopsin C increased ALP activity and bone nodule formation in cultured osteoblasts. Instead of stimulating osteoblastogenesis, (+)-vitisin A dramatically repressed osteoclasts differentiation and bone resorption. The results suggested VtR composed of diverse components to reciprocally drive osteoblastogenesis and interdict osteoclastogenesis may serve as a potential botanic drug for osteoporosis therapy.

13.
J Asian Nat Prod Res ; 14(7): 704-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22582907

RESUMO

A new auronol, cudrauronol (1), was isolated from the roots of Cudrania cochinchinensis along with 10 known compounds, 1,3,5-trihydroxy-4-prenylxanthone (2), 1,3,7-trihydroxy-4-prenylxanthone (3), 3,4',5,7-tetrahydroxydihydroflavonol (4), kaempferol (5), 3,6-dihydroxy-1,5-dimethoxyxanthone (6), 2',4',5,7-tetrahydroxyflavanolol (7), 3,7-dihydroxy-1-methoxyxanthone (8), 1,3,5-trihydroxyxanthone (9), cudraflavone B (10), and 2'-oxyresveratrol (11). Compounds 1-8 were evaluated for anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 2-5 were more active than aminoguanidine, with IC(50) values of 8.8, 23.2, 27.1, and 11.9 µM, respectively.


Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Benzofuranos/isolamento & purificação , Moraceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/biossíntese , Raízes de Plantas/química , Taiwan
14.
Phytomedicine ; 19(6): 551-61, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22397994

RESUMO

Neobavaisoflavone (NBIF) is an isoflavone isolated from Psoralea corylifolia L, a plant claimed to have osteogenic activity and used to treat bone fractures, osteomalacia and osteoporosis. The present results showed that NBIF concentration-dependently promoted osteogenesis in MC3T3-E1cells, demonstrated by notable enhancement of alkaline phosphatase (ALP) activity, increase of bone-specific matrix proteins expression including type I collagen (Col-I), osteocalcin (OCN) and bone sialoprotein (BSP), and formation of bone nodules. However, cell proliferation in the presence of NBIF was not affected. Results also demonstrated that NBIF up-regulated the expression of runt-related transcription factor 2 (Runx2) and Osterix (Osx), the bone-specific transcription factors participating in regulation of bone marker genes expression. Application of p38 inhibitor SB203580 repressed not only NBIF-induced activation of ALP, the expression of Col-I, OCN and BSP, but also the matrix proteins mineralization. Western blot analysis further revealed that NBIF increased the phosphorylated level of p38 concentration-dependently. Additionally, inhibition of p38 abolished the stimulatory effect of NBIF on the expression of Runx2 and Osx. Taken together, the osteogenic activity of NBIF might probably act through activation of p38-dependent signaling pathway to up-regulate the mRNA levels of Runx2 and Osx then stimulate bone matrix proteins expression. The beneficial effect of NBIF on mineralization demonstrated that NBIF represented as an active component existed in P. corylifolia and might be a potential anabolic agent to treat bone loss-associated diseases.


Assuntos
Matriz Óssea/efeitos dos fármacos , Isoflavonas/farmacologia , Osteogênese/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Psoralea/química , Fatores de Transcrição/metabolismo , Células 3T3 , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/genética , Animais , Matriz Óssea/enzimologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Avaliação de Medicamentos , Receptor alfa de Estrogênio/metabolismo , Expressão Gênica/efeitos dos fármacos , Camundongos , Osteoblastos/metabolismo , Óleos Vegetais/farmacologia , RNA Mensageiro/metabolismo , Fator de Transcrição Sp7 , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Eur J Pharmacol ; 676(1-3): 26-33, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22192930

RESUMO

We have reported previously that ugonin K, a flavonoid isolated from Helminthostachys zeylanica (L.) Hook, potently induces cell differentiation and mineralization of MC3T3-E1 mouse osteoblast-like cells. Here we aimed to elucidate whether ugonin K evoked osteogenesis required interaction with estrogen receptor. Results showed that ugonin K induced increases in alkaline phosphatase (ALP) activity, expressions of bone sialoprotein (BSP) and osteocalcin (OCN), and subsequent bone nodule formation were concentration-dependently inhibited by estrogen receptor antagonist ICI 182,780, suggesting that an estrogen receptor-dependent pathway was involved. In the presence of ICI 182,780, ugonin K induced up-regulation of the expressions of runt-related transcription factor 2 (Runx2) and osterix was also significantly repressed. Numerous studies have demonstrated that estrogens induced rapid and transient activation of the c-Src phosphorylation cascade. We found that ugonin K indeed raised the phosphorylated level of c-Src and such phosphorylation was significantly attenuated by ICI 182,780 treatment. Application of c-Src specific inhibitor PP2 concentration-dependently repressed ugonin K-induced osteogenesis. In the nuclear translocation assay, results showed that ugonin K increased the nuclear level of estrogen receptor-α protein, suggesting that an enhanced transcriptional activity might be observed. Excepting MC3T3-E1 cells, results obtained from ALP activity assay revealed that ugonin K also stimulated osteoblastic differentiation of human MG-63 osteosarcoma cells and rat primary osteoblasts isolated from femora. Our results demonstrate that ugonin K stimulated osteogenesis might act through an estrogen receptor-dependent activation of a non-classical signaling pathway mediated by phosphorylation of c-Src. Moreover, a transactivation potential toward estrogen receptor-α through a classical pathway might not be precluded.


Assuntos
Flavonoides/farmacologia , Osteogênese/efeitos dos fármacos , Proteínas Tirosina Quinases/metabolismo , Receptores Estrogênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Proteína Tirosina Quinase CSK , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Estradiol/análogos & derivados , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Fulvestranto , Humanos , Camundongos , Especificidade de Órgãos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fator de Transcrição Sp7 , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacos , Quinases da Família src
16.
J Sex Med ; 9(4): 1027-36, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21569213

RESUMO

INTRODUCTION: Eurycoma longifolia Jack (Simaroubaceae) has the reputation as a male aphrodisiac because it is claimed to increase virility and sexual prowess. Nevertheless, whether or not E. longifolia regulates directly the muscle tone of corpus cavernosa and/or seminal vesicle (SV) remains unclear. Even until now, the compositions that could account for its aphrodisiac property are still unknown AIM: We examined the effect of 9-hydroxycanthin-6-one (9-HC-6-one), a ß-carboline alkaloid isolated from E. longifolia, on penile erection and ejaculation, and further elucidated the mechanism of action. MAIN OUTCOME MEASURES: 9-HC-6-one induces penile erection and delays ejaculation. METHODS: Drug's effect was studied on rat corpus cavernosum (CC) and SV in vitro, and on the changes in intracavernosal pressure (ICP) after IC injection and intraluminal pressure (ILP) of the SV after hypogastric nerve stimulation (HNS), respectively. RESULTS: 9-HC-6-one relaxed significantly phenylephrine (PE)-precontracted CC. Such response was not attenuated by endothelium disruption, N(G) -nitro-L-arginine methyl ester, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one treatment, suggesting that a nitric oxide/cyclic guanosine monophosphate-dependent pathway was precluded. 9-HC-6-one attenuated PE-induced contraction by blocking cell surface and internal calcium channels with a higher potency for internal calcium release. This compound also antagonized calcium-evoked contraction in Ca2+ -free, high K+ -depolarizing condition, suggesting that interfering with the entry of calcium through voltage-dependent channels also contributed to 9-HC-6-one-induced corporal relaxation. After IC application of 9-HC-6-one, a significant rise in ICP was observed as compared with the application of normal saline. 9-HC-6-one relaxed significantly norepinephrine (NE)- and KCl-precontracted SV, and antagonized NE-induced oscillatory contraction as potent as clomipramine. Finally, the HNS-evoked increase in ILP was dose-dependently repressed after challenge by 9-HC-6-one. CONCLUSION: 9-HC-6-one might be the active component that contributed to the aphrodisiac effect of E. longifolia by antagonizing the smooth muscle tone of CC as well as SV probably through interfering with Ca2+ mobilization.


Assuntos
Afrodisíacos/farmacologia , Carbolinas/farmacologia , Ejaculação/efeitos dos fármacos , Eurycoma/química , Alcaloides Indólicos/farmacologia , Ereção Peniana/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Glândulas Seminais/efeitos dos fármacos , Animais , Canais de Cálcio/efeitos dos fármacos , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Pênis/irrigação sanguínea , Ratos
17.
Eur J Pharmacol ; 668(3): 383-9, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21806985

RESUMO

Ugonin K is a flavonoid isolated from the roots of Helminthostachys zeylanica, a folk medicine used to strengthen bone mass and cure bone fracture. It is of interest to determine whether ugonin K has beneficial effect on osteoblast maturation. In this study, MC3T3-E1 osteoblasts were treated with ugonin K. Cell differentiation and mineralization were identified by alkaline phosphatase (ALP) activity and Alizarin red S staining, respectively. RT-PCR and Western blot were used to analyze osteoblast-associated gene expression and signaling pathways. Our results showed that ugonin K significantly induced the increase of ALP activity, expressions of bone sialoprotein (BSP) and osteocalcin (OCN), and mineralization. The mRNA expressions of the transcription factors Runx2 and osterix were also up-regulated by ugonin K. Ugonin K increased the phosphorylated level of p38 and ERK, respectively. In the presence of SB203580, ugonin K induced expressions of Runx2 and osterix, ALP activity, BSP level and bone nodule formation were all completely inhibited, but ugonin K induced OCN expression was not affected. On the other hand, ugonin K-induced ALP activity and mineralization were mildly attenuated by PD98059, but the over-expressed Runx2, osterix, BSP and OCN also were significantly repressed by PD98059. These suggested that both p38 and ERK participate in regulating ugonin K evoked osteogenesis but p38 seemed to play a more important role. Take together, the potential anabolic effect of ugonin K on bone might act through activations of p38- and ERK-mediated Runx2 and osterix expressions to induce the synthesis of osteoids and formation of bone nodule.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Flavonoides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Fatores de Transcrição/genética , Células 3T3 , Animais , Matriz Óssea/efeitos dos fármacos , Matriz Óssea/metabolismo , Cálcio/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteoblastos/enzimologia , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição Sp7 , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-21799692

RESUMO

Evodia rutaecarpa is commonly used as an anti-inflammatory herbal remedy in traditional Chinese medicine. In this study, the ethanol extract of E. rutaecarpa (ER) and three major quinazoline alkaloids dehydroevodiamine (DeHE), evodiamine (Evo) and rutaecarpine (Rut), isolated from ER were employed to study their inhibitory effects against influenza A virus (H1N1)-induced chemokines production in A549 lung epithelial cells as well as on chemokines-evoked cell recruitment in HL-60-differentiated macrophages. The results showed that ER was a potent inhibitor of RANTES secretion by H1N1-inoculated A549 cells (IC(50): 1.9 ± 0.4 µg ml(-1)). Three alkaloids, although to differing extents, all concentration dependent, inhibited H1N1-induced RANTES production with Evo consistently being the most potent among these active components. ER also moderately and significantly inhibited H1N1-stimulated MCP-1 production in A549 cells. This was mimicked by Evo and Rut, but not DeHE. In the macrophage recruitment assay, both RANTES and MCP-1 markedly evoked cell migration and this phenomenon was significantly suppressed by ER. Evo and Rut, but not DeHE, also had the ability to inhibit cell migration toward RANTES and MCP-1, respectively. In summary, three major alkaloids displayed different potentials for inhibiting chemokines secretion and subsequently cell migration, which could partially explain the activity of ER. As an effective agent to suppress H1N1-induced chemokines production and block chemokine-attracted leukocytes recruitment, E. rutaecarpa and its active components may be useful in influenza virus infection-related inflammatory disorders.

19.
Int Immunopharmacol ; 11(9): 1166-72, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21457761

RESUMO

Angelica sinensis (AS), an herb used in traditional Chinese medicine, is thought to have anti-inflammatory activities. Ligustilide is its most abundant ingredient. This study sought to determine ligustilide's effects on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Ligustilide significantly suppressed the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α). The inhibition of NO was concomitant with a decrease in the protein and mRNA levels of LPS-induced nitric oxide synthase (iNOS). Furthermore, activation of activator protein-1 (AP-1) and nuclear factor κB (NF-κB) in the nucleus and the cytosolic degradation of IκBα were abrogated by ligustilide. Ligustilide also inhibited the phosphorylation of IκB kinase (IKK) and mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). The intracellular reactive oxygen species (iROS) level was also significantly decreased. These results suggest that ligustilide exhibits anti-inflammatory activities by blocking the activation of MAPKs/IKK and the downstream transcription factors AP-1 and NF-κB, which may result from ligustilide's down-regulation of iROS production.


Assuntos
4-Butirolactona/análogos & derivados , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Transcrição RelA/antagonistas & inibidores , 4-Butirolactona/farmacologia , Animais , Linhagem Celular , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Regulação para Baixo/efeitos dos fármacos , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase 4/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Macrófagos/metabolismo , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
20.
Bioorg Med Chem ; 19(8): 2751-6, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21441032

RESUMO

Some chalcones exert potent anti-inflammatory activities. Mannich bases of heterocyclic chalcones inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-γ stimulated RAW 264.7 macrophages. Also Formyl-Met-Leu-Phe and cytochalasin B induced superoxide anion generation (O2·-) and elastase release in human neutrophils. Mannich bases of heterocyclic chalcone analogs exhibited potent inhibitory effects on NO production with IC(50) values ranges between 10.5 and 0.018 µM, O2·- generation (IC(50) 39.87-0.68 µM) and elastase release (IC(50) 39.74-0.95 µM). Compound 29 (IC(50) 0.055 µM) and 34 (IC(50) 0.018 µM) were showed excellent inhibition on NO production. On the other hand, compounds 2 and 8 showed potent inhibition on O2·- generation and elastase release. Therefore, these four compounds may be new leads for development of anti-inflammatory activities. The structure-activity relationships are also discussed.


Assuntos
Chalconas/farmacologia , Macrófagos/metabolismo , Neutrófilos/metabolismo , Óxido Nítrico/biossíntese , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Animais , Anti-Inflamatórios , Chalconas/química , Compostos Heterocíclicos , Humanos , Ativação de Macrófagos , Camundongos , Relação Estrutura-Atividade
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