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1.
Int J Mol Sci ; 24(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38139137

RESUMO

Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai-a naturally growing species in South Korea-and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases.


Assuntos
Agrimonia , Humanos , Linfócitos T , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologia
2.
Immunopharmacol Immunotoxicol ; 44(3): 347-354, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35297281

RESUMO

BACKGROUND: Respiratory diseases due to particulate matter are a serious health issue. We sought to investigate the efficacy of isopanepoxydone (ISO) isolated from the Panus rudis as a therapeutic against particulate matter-induced respiratory complications. MATERIALS AND METHODS: ISO was isolated from a culture broth of Panus rudis using solvent partition, silica gel, and column chromatography, and high-performance liquid chromatography. Its chemical structure was determined spectroscopically. Murine alveolar macrophages (MH-S) were treated with ISO to investigate the inhibition of nitric oxide (NO) while cytotoxicity was investigated via a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of pro-inflammatory mediators, cytokines, and protein expression levels in the oxidative protective and inflammasome pathway were also investigated. Reactive oxygen species in MH-S cells were investigated using 2',7'-dichlorofluorescein diacetate while immunofluorescence was performed to investigate the expression of activated apoptosis-associated speck-like proteins (ASC) containing a caspase recruitment domain in MH-S cells. RESULTS: ISO effectively inhibited CFA-induced NO production with no cytotoxicity on MH-S cells and pro-inflammatory mediators and cytokines were also inhibited (except tumor necrosis factor α and interleukin-6). ISO enhanced the protein expression of nuclear factor erythroid 2-related factor 2, while suppressing proteins in the inflammasome pathway, but did not suppress the expression of nuclear factor-kappa B. ISO also reduced detectable ROS other than preventing the activation of ASC. CONCLUSION: Pathways of action of ISO in MH-S cells that prevent oxidative damage and suppress the expression of proteins in the inflammasome pathway were investigated. ISO may be developed as a treatment for respiratory inflammation.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Inflamassomos , Macrófagos Alveolares , Fator 2 Relacionado a NF-E2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Citocinas/metabolismo , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Material Particulado , Polyporales/química
3.
Mar Drugs ; 19(8)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34436289

RESUMO

Ulva lactuca (U. lactuca) is a green alga distributed worldwide and used as a food and cosmetic material. In our previous study, we determined the effects of U. lactuca methanol extracts on the UVB-induced DNA repair. In the present study, we fractionated U. lactuca methanol extracts to identify the effective compound for the DNA repair. MTT assay demonstrated that (+)-epiloliolide showed no cytotoxicity up to 100 µM in BJ-5ta human dermal fibroblast. Upon no treatment, exposure to UVB 400 J/m2 decreased cell viability by 45%, whereas (+)-epiloliolide treatment for 24 h after UVB exposure significantly increased the cell viability. In GO and GESA analysis, a number of differentially expressed genes were uniquely expressed in (+)-epiloliolide treated cells, which were enriched in the p53 signaling pathway and excision repair. Immunofluorescence demonstrated that (+)-epiloliolide increased the nuclear localization of p53. Comet assay demonstrated that (+)-epiloliolide decreased tail moment increased by UVB. Western blot analysis demonstrated that (+)-epiloliolide decreased the levels of p-p53, p21, Bax, and Bim, but increased that of Bcl-2. Reverse transcription PCR (RT-PCR) demonstrated that (+)-epiloliolide decreased the levels of MMP 1, 9, and 13, but increased that of COL1A1. These results suggest that (+)-epiloliolide regulates p53 activity and has protective effects against UVB.


Assuntos
Benzofuranos/farmacologia , Fibroblastos/efeitos dos fármacos , Envelhecimento da Pele , Proteína Supressora de Tumor p53/efeitos dos fármacos , Ulva , Organismos Aquáticos , Humanos , Fitoterapia , Raios Ultravioleta
4.
Phytother Res ; 34(12): 3200-3210, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32779813

RESUMO

Rosa rugosa Thunb., is as a medicinal plant known for anti-diabetic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of in R. rugosa extract (95% EtOH) remain unknown. Here, we hypothesized that terpenoid structure, the most abundant constituents in R. rugosa extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-13) and newly purified 11-methoxy polisin A, and 13-methoxy bisaborosaol F using NMR and ESI-MS and to screened their effects on NO production in LPS-induced macrophages. Rugosic acid A (RA) induced to ameliorate NO production, iNOS, and pro-inflammatory cytokines associated with the NF-κB. And, RA suppressed IL-6 secretion and IL-6-mediated STAT3 activation in LPS-mediated inflammation. In addition, RA was evaluated in LPS-mediated acute lung injury (ALI) model similar to acute pneumonia. Our results suggested that RA was suppressed to translocate nuclear NF-κB and IL-6-mediated STAT3 activation. Finally, RA led to amelioration of ALI by decreasing myeloperoxidase (MPO) and inhibiting phosphorylation of NF-κB and STAT3. Our group originally found that R. rugosa extract had new methoxy compounds and RA may be alternative natural agent for acute pneumonia similar to severe acute respiratory syndrome by coronavirus.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Interleucina-6/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Rosa , Fator de Transcrição STAT3/antagonistas & inibidores , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Humanos , Lipopolissacarídeos , Camundongos Endogâmicos BALB C
5.
Molecules ; 25(21)2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114669

RESUMO

Cancer stem cells have certain characteristics, such as self-renewal, differentiation, and drug resistance, which are related to tumor progression, maintenance, recurrence, and metastasis. In our study, we targeted breast cancer stem cells (BCSCs) using a natural compound, coriolic acid, from Salicornia herbacea L. This compound was isolated by mammosphere formation inhibition bioassay-guided fractionation and identified by using NMR spectroscopy and electrospray ionization mass spectrometry. Coriolic acid inhibited the formation of mammospheres and induced BCSC apoptosis. It also decreased the subpopulation of CD44high/CD24low cells, a cancer stem cell (CSC) phenotype, and specific genes related to CSCs, such as Nanog,Oct4, and CD44. Coriolic acid decreased the transcriptional and translational levels of the c-Myc gene, which is a CSC survival factor. These results indicated that coriolic acid could be a novel compound to target BCSCs via regulation of c-Myc.


Assuntos
Neoplasias da Mama/patologia , Chenopodiaceae/química , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
6.
Molecules ; 25(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977636

RESUMO

The presence of breast cancer stem cells (BCSCs) induces the aggressive progression and recurrence of breast cancer. These cells are drug resistant, have the capacity to self-renew and differentiate and are involved in recurrence and metastasis, suggesting that targeting BCSCs may improve treatment efficacy. In this report, methanol extracts of carrot root were purified by means of silica gel, Sephadex LH-20, and preparative high-performance liquid chromatography to isolate a compound targeting mammosphere formation. We isolated the compound 6-methoxymellein, which inhibits the proliferation and migration of breast cancer cells, reduces mammosphere growth, decreases the proportion of CD44+/CD24- cells in breast cancer cells and decreases the expression of stemness-associated proteins c-Myc, Sox-2 and Oct4. 6-Methoxymellein reduces the nuclear localization of nuclear factor-κB (NF-κB) subunit p65 and p50. Subsequently, 6-methoxymellein decreases the mRNA transcription and secretion of IL-6 and IL-8. Our data suggest that 6-methoxymellein may be an anticancer agent that inhibits BCSCs via NF-κB/IL-6 and IL-8 regulation.


Assuntos
Neoplasias da Mama/patologia , Daucus carota/química , Isocumarinas/isolamento & purificação , Isocumarinas/farmacologia , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Células MCF-7 , Células-Tronco Neoplásicas/patologia
7.
Molecules ; 25(11)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503228

RESUMO

Breast cancer stem cells (BCSCs) are responsible for tumor chemoresistance and recurrence. Targeting CSCs using natural compounds is a novel approach for cancer therapy. A CSC-inhibiting compound was purified from citrus extracts using silica gel, gel filtration and high-pressure liquid chromatography. The purified compound was identified as tangeretin by using nuclear magnetic resonance (NMR). Tangeretin inhibited cell proliferation, CSC formation and tumor growth, and modestly induced apoptosis in CSCs. The frequency of a subpopulation with a CSC phenotype (CD44+/CD24-) was reduced by tangeretin. Tangeretin reduced the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3). Our results in this study show that tangeretin inhibits the Stat3 signaling pathway and induces CSC death, indicating that tangeretin may be a potential natural compound that targets breast cancer cells and CSCs.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Citrus/química , Flavonas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Apoptose , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Molecules ; 25(13)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32630026

RESUMO

Breast cancer is a major health problem that affects lives worldwide. Breast cancer stem cells (BCSCs) are small subpopulations of cells with capacities for drug resistance, self-renewal, recurrence, metastasis, and differentiation. Herein, powder extracts of beetroot were subjected to silica gel, gel filtration, thin layer chromatography (TLC), and preparatory high-pressure liquid chromatography (HPLC) for isolation of one compound, based on activity-guided purification using tumorsphere formation assays. The purified compound was identified as betavulgarin, using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI) mass spectrometry. Betavulgarin suppressed the proliferation, migration, colony formation, and mammosphere formation of breast cancer cells and reduced the size of the CD44+/CD24- subpopulation and the expression of the self-renewal-related genes, C-Myc, Nanog, and Oct4. This compound decreased the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3) and reduced the mRNA and protein levels of sex determining region Y (SRY)-box 2 (SOX2), in mammospheres. These data suggest that betavulgarin inhibit the Stat3/Sox2 signaling pathway and induces BCSC death, indicating betavulgarin might be an anticancer agent against breast cancer cells and BCSCs.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzopiranos/farmacologia , Beta vulgaris/química , Neoplasias da Mama/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Benzopiranos/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas
9.
Molecules ; 24(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703464

RESUMO

Portulaca oleracea is as a medicinal plant known for its neuroprotective, hepatoprotective, antidiabetic, antioxidant, anticancer, antimicrobial, antiulcerogenic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of P. oleracea extract (95% EtOH) remain unknown. Here, we hypothesized that alkaloids, the most abundant constituents in P. oleracea extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-22) using nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) and screened their effects on NO production in lipopolysaccharide (LPS)-induced macrophages. Compound 20, 1-carbomethoxy-ß-carboline, as an alkaloid structure, ameliorated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and proinflammatory cytokines associated with the mitogen-activated protein kinase (MAPK) pathways, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Subsequently, we observed that compound 20 suppressed nuclear translocation of nuclear factor κB (NF-κB) using immunocytochemistry. Moreover, we recently reported that compound 8, trans-N-feruloyl-3', 7'-dimethoxytyramine, was originally purified from P. oleracea extracts. Our results suggest that 1-carbomethoxy-ß-carboline, the most effective anti-inflammatory agent among alkaloids in the 95% EtOH extract of P. oleracea, was suppressing the MAPK pathway and nuclear translocation of NF-κB. Therefore, P. oleracea extracts and specifically 1-carbomethoxy-ß-carboline may be novel therapeutic candidates for the treatment of inflammatory diseases associated with the activation of MAPKs and NF-κB.


Assuntos
Anti-Inflamatórios , Carbolinas , Núcleo Celular/metabolismo , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Portulaca/química , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Carbolinas/química , Carbolinas/isolamento & purificação , Carbolinas/farmacologia , Núcleo Celular/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , MAP Quinase Quinase 4/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Pak J Pharm Sci ; 32(5): 1919-1925, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31813853

RESUMO

Inflammation is an aggregate of different pathologic responses in body that leads to life threatening conditions if not combated at early stages. A variety of chemical medications from low quality to high quality are available in market for treatment of inflammation. However the side effects posed by these medications cannot be ignored. Here in our study we have shown for the first time, the anti-inflammatory effects of SBF compound that is obtained from wild mushroom species that are Acremonium sp. HKI 0230 and Coprinus echinosporus. We employed Nitric oxide determination, cell viability assay, RT-PCR and western blot analysis to check the anti-inflammatory effects of SBF. The antioxidant activity of this compound has been studied in detail in past, but our results have shown that SBF potently suppressed the Nitric oxide production (NO) without any cytotoxicity to the model cell line; RAW 264.7 cells. It also inhibited the production of major proinflammatory mediators and cytokines i.e. iNOS, COX-2, IL-1ß, IL-6 and TNF-α. SBF elicited its anti-inflammatory effects via the canonical NF-κB and MAPK pathway. Taken together, our results have shown that SBF exhibits excellent anti-inflammatory activity in vitro and further experimentations may warrant its application as a commercial herbal remedy for inflammation related anomalies.


Assuntos
Acremonium/química , Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Coprinus/química , Inflamação/tratamento farmacológico , Compostos de Espiro/farmacologia , Animais , Linhagem Celular , Citocinas/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
11.
Mol Carcinog ; 57(11): 1467-1479, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29964299

RESUMO

Cancer stem cells (CSCs) as a subpopulation of cancer cells are drug-resistant and radiation-resistant cancer cells to be responsible for tumor progress, maintenance and recurrence of cancer, and metastasis. This study isolated and investigated a new cancer stem cell (CSC) inhibitor derived from lactic acid fermentation products using culture broth with 2% aronia juice. The anti-CSC activity of aronia-cultured broth was significantly higher than that of the control. Activity-guided fractionation and repeated chromatographic preparation led to the isolation of one compound. Using nuclear magnetic resonance and ESI mass spectrometry, we identified the isolated compound as catechol. In this study, we report that aronia-fermented catechol has a novel inhibitory effect on human breast CSCs. Catechol inhibited breast cancer cell proliferation and mammosphere formation in a dose-dependent manner. This compound reduced the CD44high /CD24low subpopulation, ALDH-expressing cell population and the self-renewal-related genes nanog, sox2, and oct4. Catechol preferentially reduced mRNA transcripts and protein levels of Stat3 and did not induce c-Myc degradation. These findings support the novel utilization of catechol for breast cancer therapy via the Stat3/IL-6 signaling pathway. Our results suggest that catechol can be used for breast cancer therapy and that Stat3 expression is a marker of CSCs. Catechol inhibited Stat3 signaling by reducing Stat3 expression and secreted IL-6, a CSC survival factor. These findings support the novel utilization of catechol for breast cancer therapy via Stat3/IL-6 signaling.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Catecóis/farmacologia , Fermentação , Sucos de Frutas e Vegetais , Interleucina-6/metabolismo , Lactobacillales , Photinia/química , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/biossíntese , Antineoplásicos Fitogênicos/química , Biomarcadores , Catecóis/química , Catecóis/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sucos de Frutas e Vegetais/análise , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Humanos , Imunofenotipagem , Lactobacillales/metabolismo , Estrutura Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo
12.
Proc Natl Acad Sci U S A ; 112(27): 8278-83, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26056295

RESUMO

Leinamycin (LNM) is a potent antitumor antibiotic produced by Streptomyces atroolivaceus S-140, featuring an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. Upon reductive activation in the presence of cellular thiols, LNM exerts its antitumor activity by an episulfonium ion-mediated DNA alkylation. Previously, we have cloned the lnm gene cluster from S. atroolivaceus S-140 and characterized the biosynthetic machinery responsible for the 18-membered lactam backbone and the alkyl branch at C3 of LNM. We now report the isolation and characterization of leinamycin E1 (LNM E1) from S. atroolivacues SB3033, a ΔlnmE mutant strain of S. atroolivaceus S-140. Complementary to the reductive activation of LNM by cellular thiols, LNM E1 can be oxidatively activated by cellular reactive oxygen species (ROS) to generate a similar episulfonium ion intermediate, thereby alkylating DNA and leading to eventual cell death. The feasibility of exploiting LNM E1 as an anticancer prodrug activated by ROS was demonstrated in two prostate cancer cell lines, LNCaP and DU-145. Because many cancer cells are under higher cellular oxidative stress with increased levels of ROS than normal cells, these findings support the idea of exploiting ROS as a means to target cancer cells and highlight LNM E1 as a novel lead for the development of anticancer prodrugs activated by ROS. The structure of LNM E1 also reveals critical new insights into LNM biosynthesis, setting the stage to investigate sulfur incorporation, as well as the tailoring steps that convert the nascent hybrid peptide-polyketide biosynthetic intermediate into LNM.


Assuntos
Antineoplásicos/metabolismo , Lactamas/metabolismo , Macrolídeos/metabolismo , Pró-Fármacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiazóis/metabolismo , Tionas/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Lactamas/química , Macrolídeos/química , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Streptomyces/genética , Streptomyces/metabolismo , Tiazóis/química , Tionas/química
13.
Int J Mol Sci ; 19(9)2018 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-30149665

RESUMO

Cancer stem cells (CSCs) are drug-resistant and radiation-resistant cancer cells that are responsible for tumor progression and maintenance, cancer recurrence, and metastasis. Targeting breast CSCs with phytochemicals is a new paradigm for cancer prevention and treatment. In this study, activity-guided fractionation from mammosphere formation inhibition assays, repeated chromatographic preparations over silica gel, preparatory thin layer chromatography, and HPLC using aronia extracts led to the isolation of one compound. Using ¹H and 13C 2-dimensional nuclear magnetic resonance (NMR) as well as electrospray ionization (ESI) mass spectrometry, the isolated compound was identified as 3-O-p-coumaroyltormentic acid. This compound inhibits breast cancer cell proliferation and mammosphere formation in a dose-dependent manner and reduces the CD44high/CD24low subpopulation and aldehyde dehydrogenase (ALDH)-expressing cell population as well as the expression of the self-renewal-related genes CD44, SOX2, and OCT4.3-O-p-Coumaroyltormentic acid preferentially reduced the protein levels of c-Myc, which is a CSC survival factor, by inducing c-Myc degradation. These findings indicate the novel utilization of 3-O-p-coumaroyltormentic acid for breast cancer therapy via disruption of c-Myc protein, which is a CSC survival factor.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Biomarcadores , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Antígeno CD24/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Estrutura Molecular , Rosaceae/química , Triterpenos/química
14.
Mediators Inflamm ; 2017: 7250968, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28316375

RESUMO

Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1ß, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti-inflammatory agent.


Assuntos
Inflamação/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Sesquiterpenos de Guaiano/farmacologia , Transdução de Sinais/efeitos dos fármacos
15.
Planta Med ; 82(6): 524-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26848705

RESUMO

The active constituents of Korean Papaver rhoeas bee pollen conferring neuraminidase inhibitory activities (H1N1, H3N2, and H5N1) were investigated. Six flavonoids and one alkaloid were isolated and characterized by nuclear magnetic resonance and mass spectrometry data. These included kaempferol-3-sophoroside (1), kaempferol-3-neohesperidoside (2), kaempferol-3-sambubioside (3), kaempferol-3-glucoside (4), quercetin-3-sophoroside (5), luteolin (6), and chelianthifoline (7). All compounds showed neuraminidase inhibitory activities with IC50 values ranging from 10.7 to 151.1 µM. The most potent neuraminidase inhibitor was luteolin, which was the dominant content in the ethyl acetate fraction. All tested compounds displayed noncompetitive inhibition of H3N2 neuraminidase. Furthermore, compounds 1-7 all reduced the severity of virally induced cytopathic effects as determined by the Madin-Darby canine kidney cell-based assay showing antiviral activity with IC50 values ranging from 10.7 to 33.4 µM (zanamivir: 58.3 µM). The active compounds were quantified by high-performance liquid chromatography, and the total amount of compounds 1-7 made up about 0.592 g/100 g bee pollen, contributing a rich resource of a natural antiviral product.


Assuntos
Antivirais/química , Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , Neuraminidase/antagonistas & inibidores , Papaver/química , Pólen/química , Animais , Abelhas , Cães , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/química , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Células Madin Darby de Rim Canino/efeitos dos fármacos , Células Madin Darby de Rim Canino/virologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular
16.
Int J Syst Evol Microbiol ; 65(Pt 4): 1268-1273, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25634943

RESUMO

A Gram-stain-negative, halophilic bacterium, designated strain BH195(T), was isolated from the sediment of the solar saltern pond located in Gomso, Republic of Korea. Strain BH195(T) was a strictly aerobic, non-motile rod, which grew at pH 3.5-10.5 (optimum, pH 7.5), at 4-55 °C (optimum, 30 °C) and at salinities of 0.5-11% (w/v) NaCl [optimum, 2-3% (w/v) NaCl]. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that strain BH195(T) belongs to the genus Idiomarina , showing the highest sequence similarity to Idiomarina salinarum ISL-52(T) (97.4%), Idiomarina homiensis PO-M2(T) (96.8%), Idiomarina aestuarii KYW314(T) (96.7%), and Idiomarina tainanensis PIN1(T) (96.7%). The major cellular fatty acids of strain BH195(T) were iso-C(11 : 0) 3-OH, iso-C(15 : 0) and iso-C(11 : 0). The DNA G+C content was 51.3 mol% and the major respiratory quinone was ubiquinone 8. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unknown phospholipid. DNA-DNA relatedness between strain BH195(T) and I. salinarum KCTC 12971(T) was 33%. On the basis of this polyphasic analysis, strain BH195(T) represents a novel species of the genus Idiomarina for which the name Idiomarina halophila sp. nov. is proposed. The type strain is BH195(T) ( = KACC 17610(T) = NCAIM B 02544(T)).


Assuntos
Alteromonadaceae/classificação , Filogenia , Salinidade , Microbiologia da Água , Alteromonadaceae/genética , Alteromonadaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/química
17.
Int J Syst Evol Microbiol ; 65(12): 4792-4799, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26431725

RESUMO

A Gram-stain-negative, halotolerant and alkalitolerant bacterium, designated strain BH103T, was isolated from saltern soil in Gomso, Korea. Cells of strain BH103T were strictly aerobic, motile, straight rods and grew at pH 7.0-10.8 (optimum, pH 8.5), at 10-55 °C (optimum, 28 °C) and at salinities of 0-23 % (w/v) NaCl (optimum, 14 % NaCl). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain BH103T belongs to the genus Halomonas, showing highest sequence similarity to Halomonas boliviensis LC1T (97.7 %), Halomonas neptunia Eplume1T (97.7 %), Halomonas variabilis IIIT (97.7 %), Halomonas alkaliantarctica CRSST (97.7 %), Halomonas olivaria TYRC17T (97.5 %), Halomonas titanicae BH1T (97.2 %) and Halomonas sulfidaeris Esulfide1T (96.2 %). The predominant ubiquinone was Q-9. The major fatty acids were C18 : 1ω7c, C16 : 1ω7c and/or iso-C15 : 0 2-OH, C16 : 0 and C12 : 0 3-OH. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, aminophospholipid and an unknown phospholipid. The DNA G+C content of this novel isolate was 54.7 mol%. DNA-DNA relatedness between strain BH103T and H. boliviensis KACC 16615T, H. neptunia KCTC 2888T, H. variabilis KCTC 2889T, H. alkaliantarctica KCTC 22844T, H. olivaria DSM 19074T, H. titanicae JCM 16411T and H. sulfidaeris DSM 15722T was 45, 41, 39, 32, 38, 45 and 35 %, respectively. On the basis of polyphasic analysis from this study, strain BH103T represents a novel species of the genus Halomonas, for which the name Halomonas salicampi sp. nov. is proposed. The type strain is BH103T ( = KACC 17609T = NBRC 109914T = NCAIM B 02528T).


Assuntos
Halomonas/classificação , Filogenia , Salinidade , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Halomonas/genética , Halomonas/isolamento & purificação , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/química
18.
Int J Syst Evol Microbiol ; 65(Pt 2): 375-380, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25368138

RESUMO

A Gram-stain-positive, moderately halophilic bacterium, designated BH043(T), was isolated from saltern soil of Gomso in Korea. Cells were motile rods, producing ellipsoidal endospores at a terminal position in swollen sporangia. Strain BH043(T) was strictly aerobic, grew at pH 6.0-10.0 (optimal growth at pH 7.5), at 10-55 °C (optimal growth at 30 °C) and at salinities of 1-20 % (w/v) NaCl, growing optimally with 7 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain BH043(T) belongs to the family Bacillaceae and was most closely related to the type strains of the five recognized species of the genus Pontibacillus, showing sequence similarity to Pontibacillus yanchengensis Y32(T) (97.5 % similarity), Pontibacillus marinus BH030004(T) (97.4 %), Pontibacillus chungwhensis BH030062(T) (97.0 %), Pontibacillus litoralis JSM 072002(T) (96.4 %) and Pontibacillus halophilus JSM 076056(T) (96.2 %). The major cellular fatty acids of strain BH043(T) were iso-C15 : 0 and anteiso-C15 : 0. The genomic DNA G+C content was 42.5 mol%. The major isoprenoid quinone was MK-7 and meso-diaminopimelic acid was present in the cell-wall peptidoglycan as the diagnostic diamino acid. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. DNA-DNA relatedness between strain BH043(T) and the type strains of other species of the genus Pontibacillus, P. yanchengensis CGMCC 1.10680(T) and P. marinus KCTC 3917(T) and P. chungwhensis KCTC 3890(T), was 35, 24 and 18 %, respectively. On the basis of polyphasic analysis from this study, strain BH043(T) represents a novel species of the genus Pontibacillus for which the name Pontibacillus salicampi sp. nov. is proposed. The type strain is BH043(T) ( = KACC 17607(T) = NBRC 109831(T) = NCAIM B.02529(T)).


Assuntos
Bacillaceae/classificação , Filogenia , Microbiologia do Solo , Bacillaceae/genética , Bacillaceae/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Peptidoglicano/química , RNA Ribossômico 16S/genética , República da Coreia , Salinidade , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Bioorg Med Chem Lett ; 25(16): 3256-60, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26077494
20.
Bioorg Med Chem Lett ; 25(2): 307-9, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25479772

RESUMO

Syringaresinol exists either exclusively as one enantiomer or enantiomeric mixtures in plant foods. We found that (+)-syringaresinol, but not (-)-syringaresinol, upregulates silent information regulator two ortholog 1 (SIRT1) gene expression, and thus, Panax ginseng berry with predominantly high contents of (+)-syringaresinol exhibits higher activity in inducing SIRT1 gene expression than Acanthopanax senticosus Harms stem with almost equal proportion of the two enantiomers. These findings highlight the importance of the absolute configuration of syringaresinol for the biological activity.


Assuntos
Eleutherococcus/química , Frutas/química , Furanos/farmacologia , Lignanas/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Sirtuína 1/genética , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 1/metabolismo , Estereoisomerismo , Ressonância de Plasmônio de Superfície
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