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1.
Int J Mol Sci ; 24(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36613533

RESUMO

This study was conducted to compare the synbiotic activity between Corni fructus (C. fructus) and Limosilactobacillus reuteri (L. reuteri) on dextran sulfate sodium (DSS)-induced colitis and cognitive dysfunction in C57BL/6 mice. C. fructus (as prebiotics, PRE), L. reuteri (as probiotics, PRO), and synbiotics (as a mixture of L. reuteri and C. fructus, SYN) were fed to mice for 3 weeks. Consumption of PRE, PRO, and SYN ameliorated colitis symptoms in body weight, large intestinal length, and serum albumin level. Moreover, SYN showed a synergistic effect on intestinal permeability and intestinal anti-inflammation response. Also, SYN significantly improved cognitive function as a result of measuring the Y-maze and passive avoidance tests in DSS-induced behavioral disorder mice. Especially, SYN also restored memory function by increasing the cholinergic system and reducing tau and amyloid ß pathology. In addition, PRE, PRO, and SYN ameliorated dysbiosis by regulating the gut microbiota and the concentration of short-chain fatty acids (SCFAs) in feces. The bioactive compounds of C. fructus were identified with quinic acid, morroniside, loganin, and cornuside, using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS2). In conclusion, synbiotic supplementation alleviated DSS-induced colitis and cognitive dysfunction by modulating gut microbiota, proinflammatory cytokines, and SCFAs production.


Assuntos
Colite , Cornus , Limosilactobacillus reuteri , Simbióticos , Camundongos , Animais , Peptídeos beta-Amiloides/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Colo/patologia
2.
Inflamm Res ; 69(2): 233-244, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31907559

RESUMO

OBJECTIVE: Recently, Rodgersia podophylla has been reported to exhibit anti-inflammatory activity. However, little is known about the potential mechanisms about its anti-inflammatory activity. We elucidated the anti-inflammatory mechanisms of leaves extracts from Rodgersia podophylla (RP-L) in RAW264.7 cells. MATERIALS AND METHODS: LPS-induced NO was measured by Griess and mRNA of pro-inflammatory mediators was analyzed by RT-PCR. Cell viability was measured using MTT assay. The protein level was analyzed by Western blot. RESULTS: RP-L significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, IL-1ß and IL-6 in LPS-stimulated RAW264.7 cells. RP-L increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of RP-L against LPS-induced NO production in RAW264.7 cells. Inhibition of p38, ROS and GSK3ß attenuated RP-L-mediated HO-1 expression. Inhibition of ROS inhibited p38 phosphorylation and GSK3ß expression induced by RP-L. In addition, inhibition of GSK3ß blocked RP-L-mediated p38 phosphorylation. RP-L induced nuclear accumulation of Nrf2, and inhibition of p38, ROS and GSK3ß abolished RP-L-mediated nuclear accumulation of Nrf2. Furthermore, RP-L blocked LPS-induced degradation of IκB-α and nuclear accumulation of p65. RP-L also attenuated LPS-induced phosphorylation of ERK1/2 and p38. In GC/MS analysis of RP-L, pyrogallol was detected as bioactive compound for anti-inflammatory activity of RP-L. Pyrogallol was observed to activate HO-1 expression through ROS/GSK3ß/p38/Nrf2/HO-1 signaling. CONCLUSIONS: Our results suggest that RP-L exerts potential anti-inflammatory activity by activating ROS/GSK3ß/p38/Nrf2/HO-1 signaling and inhibiting NF-κB and MAPK signaling in RAW264.7 cells. These findings suggest that RP-L may have great potential for the development of anti-inflammatory drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saxifragaceae/química , Transdução de Sinais/efeitos dos fármacos , Animais , Camundongos , Óxido Nítrico/biossíntese , Folhas de Planta/química , Células RAW 264.7
3.
BMC Complement Altern Med ; 19(1): 291, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684931

RESUMO

BACKGROUND: Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. METHODS: Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot. RESULTS: Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. CONCLUSIONS: These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.


Assuntos
Fator 2 Ativador da Transcrição/imunologia , Anti-Inflamatórios/farmacologia , Inflamação/imunologia , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Vaccinium/química , Fator 2 Ativador da Transcrição/genética , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Dinoprostona/imunologia , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/genética , Lipopolissacarídeos/efeitos adversos , Macrófagos/imunologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/genética , NF-kappa B/genética , Caules de Planta/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
4.
BMC Complement Altern Med ; 19(1): 310, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718640

RESUMO

BACKGROUND: Heracleum moellendorffii roots (HM-R) have been long treated for inflammatory diseases such as arthritis, backache and fever. However, an anti-inflammatory effect and the specific mechanism of HM-R were not yet clear. In this study, we for the first time explored the anti-inflammatory of HM-R. METHODS: The cytotoxicity of HM-R against RAW264.7 cells was evaluated using MTT assay. The inhibition of NO and PGE2 production by HM-R was evaluated using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The changes in mRNA or protein level following HM-R treatment were assessed by RT-PCR and Western blot analysis, respectively. RESULTS: HM-R dose-dependently blocked LPS-induced NO and PGE2 production. In addition, HM-R inhibited LPS-induced overexpression of iNOS, COX-2, IL-1ß and IL-6 in RAW264.7 cells. HM-R inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. Furthermore, HM-R inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. HM-R increased nuclear accumulation of Nrf2 and HO-1 expression. However, NAC reduced the increased nuclear accumulation of Nrf2 and HO-1 expression by HM-R. In HPLC analysis, falcarinol was detected from HM-R as an anti-inflammatory compound. CONCLUSIONS: These results indicate that HM-R may exert anti-inflammatory activity by inhibiting NF-κB and MAPK signaling, and activating ROS/Nrf2/HO-1 signaling. These findings suggest that HM-R has a potential as a natural material for the development of anti-inflammatory drugs.


Assuntos
Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Heme Oxigenase-1/imunologia , Heracleum/química , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Espécies Reativas de Oxigênio/imunologia , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Heme Oxigenase-1/genética , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Raízes de Plantas/química , Células RAW 264.7
5.
BMC Complement Altern Med ; 19(1): 43, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736789

RESUMO

BACKGROUND: Sageretia thea (S. thea) has been used as the medicinal plant for treating hepatitis and fevers in Korea and China. Recently, anticancer activity of S. thea has been reported, but the potential mechanism for the anti-cancer property of S. thea is still insufficient. Thus, we evaluated whether extracts from the leaves (STL) and branches (STB) of S. thea exert anticancer activity and elucidated its potential mechanism in SW480 cells. METHODS: MTT assay was performed for measuring cell viability. Western blot and RT-PCR were used for analyzing the level of protein and mRNA, respectively. RESULTS: Treatment of STL or STB decreased the cell viability and induced apoptosis in SW480 cells. Decreased level of cyclin D1 protein was observed in SW480 cells treated with STL or STB, but no change in cyclin D1 mRNA level was observed with the treatment of STL or STB. MG132 blocked downregulation of cyclin D1 protein by STL or STB. Thr286 phosphorylation of cyclin D1 by STL or STB occurred faster than downregulation of cyclin D1 protein in SW480 cells. When SW480 cells were transfected with T286A-cyclin D1, cyclin D1 degradation by STL or STB did not occur. Inhibition of GSK3ß and cyclin D1 nuclear export attenuated STL or STB-mediated cyclin D1 degradation. In addition, STL or STB increased HO-1 expression, and the inhibition of HO-1 attenuated the induction of apoptosis by STL or STB. HO-1 expression by STL or STB resulted from Nrf2 activation through ROS-dependent p38 activation. CONCLUSIONS: These results indicate that STL or STB may induce GSK3ß-dependent cyclin D1 degradation, and increase HO-1 expression through activating Nrf2 via ROS-dependent p38 activation, which resulted in the decrease of the viability in SW480 cells. These findings suggest that STL or STB may have great potential for the development of anti-cancer drug.


Assuntos
Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Heme Oxigenase-1/metabolismo , Extratos Vegetais/farmacologia , Rhamnaceae/química , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo
6.
Mar Drugs ; 14(4)2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-27043582

RESUMO

Phlorofucofuroeckol A (PFF-A), one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB), located between positions -147 and -85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK), glycogen synthase kinase (GSK) 3ß, and IκB kinase (IKK)-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose) polymerase (PARP) by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.


Assuntos
Fator 3 Ativador da Transcrição/genética , Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Dioxinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteína de Ligação a CREB/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Células HCT116 , Células HT29 , Humanos , Quinase I-kappa B/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos
7.
Arch Biochem Biophys ; 564: 203-10, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25447816

RESUMO

Protocatechualdehyde (PCA) is one of the important compounds found in barley, green cavendish bananas and grapevine leaves. PCA shows anti-cancer activities in breast, leukemia and colorectal cancer cells. Previous study reported that PCA exerts anti-cancer activity through down-regulating cyclin D1 and HDAC2 in human colorectal cancer cells. However, the underlying mechanisms for the expression of activating transcription factor 3 (ATF3) by PCA has not been studied. Thus, we performed in vitro study to investigate if treatment of PCA affects ATF3 expression and ATF3-mediated apoptosis in human colorectal cancer cells. PCA decreased cell viability in a dose-dependent manner in HCT116 and SW480 cells. In addition, PCA reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. Exposure of PCA activated the levels of ATF3 protein and mRNA in HCT116 and SW480 cells. Inhibition of ERK1/2/ by PD98059 and p38 by SB203580 inhibited PCA-induced ATF3 expression and transcriptional activation. ATF3-knockdown inhibited PCA-induced apoptosis and cell viability. In addition, ATF3 overexpression enhanced PCA-mediated cleavage of PARP. These findings suggest that inhibition of cell viability and apoptosis by PCA may be result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.


Assuntos
Fator 3 Ativador da Transcrição/biossíntese , Anticoagulantes/farmacologia , Apoptose/efeitos dos fármacos , Benzaldeídos/farmacologia , Catecóis/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fator 3 Ativador da Transcrição/genética , Apoptose/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas de Neoplasias/genética , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
BMC Complement Altern Med ; 14: 200, 2014 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-24962785

RESUMO

BACKGROUND: Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. METHODS: In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. RESULTS: In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3ß. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. CONCLUSIONS: These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Morus/química , Extratos Vegetais/farmacologia , Fator 3 Ativador da Transcrição/biossíntese , Fator 3 Ativador da Transcrição/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Ciclina D1/biossíntese , Ciclina D1/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
BMC Complement Altern Med ; 14: 408, 2014 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-25338635

RESUMO

BACKGROUND: Ginger leaf (GL) has long been used as a vegetable, tea and herbal medicine. However, its pharmacological properties are still poorly understood. Thus, we performed in vitro studies to evaluate anti-cancer properties of ginger leaf and then elucidate the potential mechanisms involved. METHODS: Cell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA. RESULTS: Exposure of GL to human colorectal cancer cells (HCT116, SW480 and LoVo cells) reduced the cell viability and induced apoptosis in a dose-dependent manner. In addition, GL reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. ATF3 knockdown attenuated GL-mediated apoptosis. GL increased activating transcription factor 3 (ATF3) expressions in both protein and mRNA level and activated ATF3 promoter activity, indicating transcriptional activation of ATF3 gene by GL. In addition, our data showed that GL-responsible sites might be between -318 and -85 region of the ATF3 promoter. We also observed that ERK1/2 inhibition by PD98059 attenuated GL-mediated ATF3 expression but not p38 inhibition by SB203580, indicating ERK1/2 pathway implicated in GL-induced ATF3 activation. CONCLUSIONS: These findings suggest that the reduction of cell viability and apoptosis by GL may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression through ERK1/2 activation in human colorectal cancer cells.


Assuntos
Fator 3 Ativador da Transcrição/genética , Antineoplásicos/farmacologia , Neoplasias Colorretais/genética , Extratos Vegetais/farmacologia , Folhas de Planta/química , Zingiber officinale/química , Fator 3 Ativador da Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Regiões Promotoras Genéticas , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos
10.
BMC Complement Altern Med ; 14: 487, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25494848

RESUMO

BACKGROUND: Recently, Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme. However, no specific pharmacological effects from A. distichum have been described. We performed in vitro study to evaluate anti-cancer properties of A. distichum and then elucidate the potential mechanisms. METHODS: Cell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA. RESULTS: Exposure of ethyl acetate fraction from the parts of A. distichum including flower, leaf and branch to human colorectal cancer cells, breast cancer cells and hepatocellular carcinoma reduced the cell viability. The branch extracts from A. distichum (EAFAD-B) increased the expression of activating transcription factor 3 (ATF3) and promoter activity, indicating transcriptional activation of ATF3 gene by EAFAD-B. In addition, our data showed that EAFAD-B-responsible sites might be between -147 and -85 region of the ATF3 promoter. EAFAD-B-induced ATF3 promoter activity was significantly decreased when the CREB site was deleted. However, the deletion of Ftz sites did not affect ATF3 promoter activity by EAFAD-B. We also observed that inhibition of p38MAPK and GSK3ß attenuated EAFAD-B-mediated ATF3 promoter activation. Also, EAFAD-B contributes at least in part to increase of ATF3 accumulation. CONCLUSION: These findings suggest that the anti-cancer activity of EAFAD-B may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression.


Assuntos
Fator 3 Ativador da Transcrição/biossíntese , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Oleaceae , Fitoterapia , Extratos Vegetais/uso terapêutico , Ativação Transcricional/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Extratos Vegetais/farmacologia , Regiões Promotoras Genéticas , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Plants (Basel) ; 12(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37765356

RESUMO

Cirsium setidens is commonly used as a food ingredient, and it is typically stored and distributed in a dried form to prolong its shelf life. In a previous study, a micro-oil-sprayed thermal air (MOTA) technique was developed, which effectively enhanced the rehydration properties and improved the color characteristics of Cirsium setidens after processing. Here, we investigated the relationship between the color characteristics and taste of MOTA-processed C. setidens and the effect of NaCl pretreatment, prior to processing, on the final quality of dried C. setidens. NaCl pretreatment, whether combined with the MOTA technique or not, showed improved color characteristics, in which MOTA-and NaCl+ MOTA-processed C. setidens manifested equal color characteristics. In contrast, NaCl + MOTA-processed C. setidens resulted in significantly higher values of sourness and saltiness than MOTA-processed C. setidens when the taste of the rehydrated C. setidens was examined using an electronic tongue (Astree II; Alpha MOS, Toulouse, France). Pearson correlation coefficient analysis showed that sourness and saltness were negatively correlated with Hunter a* values and positively correlated with Hunter L* and Hunter b* values, indicating that the color characteristics of dried and rehydrated C. setidens could be indicators of taste. Furthermore, the amounts of total phenol and chlorophyll were better preserved in C. setidens processed by the MOTA technique with NaCl than by the MOTA technique alone. Our data revealed that the color characteristics of dried plants are associated with the taste of processed C. setidens, and that the MOTA technique with NaCl pretreatment is a useful method for preserving health-promoting compounds during processing.

12.
Mycobiology ; 51(6): 445-451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38179119

RESUMO

Shiitake mushroom (Lentinula edodes) hold high nutritional and medicinal value as they contain an abundance of health-promoting compounds. However, the effect of long-term postharvest storage on the variation in the levels of health-promoting compounds has not been extensively studied. In this study, we investigated the changes in the levels of phenolic compounds, antioxidants, eritadenine, and ergothioneine in shiitake mushrooms stored at three different temperatures (1, 3, and 5 °C) for 4 weeks. Compared to mushrooms stored at lower temperatures, those stored at 5 °C exhibited a higher level of total phenolics in their pileus after 2 weeks of storage; however, storage at 5 °C also increased the deterioration of the fruiting body of these mushrooms. In mushrooms stored at all temperatures, the eritadenine content in the pilei tended to increase up to 2 weeks of storage. In contrast, the ergothioneine content in the pileus decreased during storage, with a significantly lower level detected in mushrooms stored at 5 °C for 4 weeks. Together, these results suggest that the mechanisms underlying the accumulation of phenolics and eritadenine may be related to mushroom deterioration during storage. Our findings indicate that the levels of health-promoting compounds in shiitake mushrooms are influenced by storage temperature, suggesting the potential to control adjustments of specific bioactive compounds by regulating storage conditions.

13.
Food Sci Nutr ; 10(9): 3034-3042, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36171791

RESUMO

As the national flower of Korea, the Hibiscus syriacus L. (Rose of Sharon) is symbolic in its abundance and is a prominent feature of Korean culture. H. syriacus has played an important role in Korea, not only as an ornamental plant but also as an essential ingredient in folk remedies through its various parts. This study aimed to characterize the nutritional and biochemical composition of each plant unit of H. syriacus "Wonhwa." The units are namely: the petals, leaves, roots, and sprouts from its seeds. According to the results each unit produced, the sprouts had the highest content of amino acids and fatty acids which adhere to the requirements of nutritionally excellent food ingredients. The petals produced high quantities of glucose, sucrose, and fumaric acid, with the highest antioxidant activity among the four units. The main bioactive compounds detected in H. syriacus extracts in the four units were o-coumaric acid, p-coumaric acid, schaftoside, isoschaftoside, apigenin-6-C-glucoside-7-o-glucoside, and kaempferol-3-O-galactoside-7-O-rhamnoside. Overall, the highest number of bioactive compounds, 2 phenolic acids and 22 flavonoids, were identified in the petals. These results suggest the possibility of excellent pharmacological activity in the petals.

14.
Plants (Basel) ; 10(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808663

RESUMO

Berchemia floribunda (Wall.) Brongn. (BF), which belongs to Rhamnaceae, is a special plant of Anmyeon Island in Korea. BF has been reported to have antioxidant and whitening effects. However, the anti-inflammatory activity of BR has not been elucidated. In this study, we evaluated the anti-inflammatory effect of leaves (BR-L), branches (BR-B) and fruit (BR-F) extracted with 70% ethanol of BR and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. BR-L showed a strong anti-inflammatory activity through the inhibition of NO production. BR-L significantly suppressed the production of the pro-inflammatory mediators such as iNOS, COX-2, IL-1ß, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells. BR-L suppressed the degradation and phosphorylation of IκB-α, which contributed to the inhibition of p65 nuclear accumulation and NF-κB activation. BR-L obstructed the phosphorylation of MAPKs (ERK1/2, p38 and JNK) in LPS-stimulated RAW264.7 cells. Consequently, these results suggest that BR-L may have great potential for the development of anti-inflammatory drugs to treat acute and chronic inflammatory disorders.

15.
Food Sci Nutr ; 9(1): 514-521, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33473312

RESUMO

Heracleum moellendorffii (H. moellendorffii) is a family of Umbelliferae and has long been used for food and medicinal purposes. However, the immune-enhancing activity of H. moellendorffii has not been studied. Thus, we evaluated in vitro immune-enhancing activity of H. moellendorffii through macrophage activation using RAW264.7 cells. Heracleum moellendorffii Root extracts (HMR) increased the production of immunomodulators such as NO, iNOS, IL-1ß, IL-6 IL-12, TNF-α, and MCP-1 and activated phagocytosis in RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by HMR. Inhibition of MAPK signaling attenuated the production of immunomodulators induced by HMR, but inhibitions of NF-κB or PI3K/AKT signaling did not affect HMR-mediated production of immunomodulators. HMR activated MAPK signaling pathway, and activation of MAPK signaling pathways by HMR was reversed by TLR2 and TLR4 inhibition. Based on the results of this study, HMR is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK signaling pathway. Therefore, it is thought that HMR has the potential to be used as an agent for enhancing immunity.

16.
J Ethnopharmacol ; 263: 113218, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32755650

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng Meyer) is a very well-known traditional herbal medicine that has long been used to enhance the body's immunity. Because it is a type of ginseng, it is believed that wild simulated ginseng (WSG) also has immune-enhancing activity. However, study on the immune-enhancing activity of WSG is quite insufficient compared to ginseng. AIM OF THE STUDY: In this study, we evaluated immune-enhancing activity of WSG through macrophage activation to provide a scientific basis for the immune enhancing activity of WSG. MATERIALS AND METHODS: The effect of WSG on viability of RAW264.7 cells was evaluated by MTT assay. The NO level was measured by Griess reagent. The expression levels of mRNA or protein in WSG-treated RAW264.7 cells were analyzed by RT-PCR and Western blot, respectively. RESULTS: WSG increased the production of immunomodulators such as NO, iNOS, COX-2, IL-1ß, IL-6 and TNF-α and activated phagocytosis in mouse macrophages RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by WSG. WSG activated MAPK, NF-κB and PI3K/AKT signaling pathways, and inhibition of such signaling activation blocked WSG-mediated production of immunomodulators. In addition, activation of MAPK, NF-κB and PI3K/AKT signaling pathways by WSG was reversed by TLR2 or TLR4 inhibition. CONCLUSION: Based on the results of this study, WSG is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, it is thought that WSG have the potential to be used as an agent for enhancing immunity.


Assuntos
Ativação de Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Panax , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Ativação de Macrófagos/fisiologia , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Células RAW 264.7
17.
Mol Med Rep ; 22(6): 5219-5230, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174016

RESUMO

Honeyberry (Lonicera caerulea) has long been used as a traditional medicine in China, Japan and northern Russia. Functional studies of honeyberry have mainly focused on the fruits, which have been reported to exert various pharmacological activities, including anti­inflammatory activity, with limited or no studies on the other parts of the plant, such as the leaves and branches. In the present study, the anti­inflammatory effects of extracts of the leaves (HBL), branches (HBB) and fruit (HBF) of honeyberry plant were evaluated in lipopolysaccharide (LPS)­stimulated RAW264.7 cells. HBL and HBB significantly inhibited the production of pro-inflammatory mediators in LPS­stimulated RAW264.7 cells, and the inhibitory effects of HBL and HBB were stronger than those of HBF. HBL and HBB blocked the nuclear accumulation of p65 independently of IκB­α. HBL did not inhibit the phosphorylation of ERK1/2 or p38; however, HBB effectively inhibited the phosphorylation of p38 but not ERK1/2. HBL and HBB increased the expression of heme oxygenase­1 (HO­1) protein by inducing the nuclear accumulation of nuclear factor erythroid 2­related factor 2 (Nrf2) through the activation of the reactive oxygen species (ROS)/p38 pathway; the reduction in inducible nitric oxide synthase (iNOS) and interleukin­1ß (IL­1ß) expression by HBL and HBB was inhibited by HO­1 knockdown. In addition, HBL and HBB increased the expression of activating transcription factor­3 (ATF3), and the reduction in iNOS and IL­1ß expression by HBL and HBB was inhibited by ATF3 knockdown. Collectively, HBL and HBB inhibited LPS­induced nuclear factor­κB activation by blocking the nuclear accumulation of p65, increasing HO­1 expression through activation of the ROS/p38/Nrf2 pathway, and increasing ATF3 expression. Furthermore, HBB inhibited LPS­induced p38 phosphorylation. These findings suggest that HBL and HBB may have great potential as natural products for the development of anti­inflammatory drugs.


Assuntos
Lonicera/metabolismo , Extratos Vegetais/farmacologia , Fator 3 Ativador da Transcrição/metabolismo , Animais , Anti-Inflamatórios/farmacologia , China , Frutas/metabolismo , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/farmacologia , Medicina Tradicional Chinesa , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/metabolismo , Células RAW 264.7/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
18.
Am J Chin Med ; 47(2): 385-403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834779

RESUMO

Sageretia thea (S. thea) commonly known as Chinese sweet plum or Chinese bird plum has been used for treating hepatitis and fevers in Korea and China. S. thea has been reported to exert anti-oxidant, anticancer and anti-human immunodeficiency virus activity. However, there is little study on the anti-inflammatory activity of S. thea. Thus, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia thea in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, IL-1 ß and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of I κ B- α and nuclear accumulation of p65, which resulted in the inhibition of NF- κ B activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing NF- κ B and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.


Assuntos
Anti-Inflamatórios , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Rhamnaceae/química , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Animais , Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Camundongos , NF-kappa B/genética , Folhas de Planta/química , Caules de Planta/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Biomol Ther (Seoul) ; 24(4): 380-6, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27068260

RESUMO

Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-κB-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of ß-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular ß-catenin protein but not mRNA. The inhibition of proteasome by MG132 and GSK3ß inhibition by SB216763 blocked silymarin-mediated downregulation of ß-catenin. In addition, silymarin increased phosphorylation of ß-catenin and a point mutation of S33Y attenuated silymarin-mediated ß-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of ß-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.

20.
Phytomedicine ; 23(2): 105-13, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26926171

RESUMO

BACKGROUND: Mulberry root bark was shown to induce cyclin D1 proteasomal degradation in the human colorectal cancer cells. Still, the molecular mechanisms whereby mulberry root bark induces cyclin D1 proteasomal degradation remain largely unknown. PURPOSE: In this study, the inhibitory effect of mulberry root bark (MRB) on the proliferation of human colorectal cancer cells and the mechanism of action were examined to evaluate its anti-cancer activity. METHODS: Anti-proliferative effect was determined by MTT assay. RT-PCR and Western blotting were used to assess the mRNA and protein expression of related proteins. RESULTS: MRB inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480 and LoVo). In addition, the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7) was suppressed by MRB treatment. However, MRB did not affect the growth of HepG-2 cells as a human hepatocellular carcinoma cell line. MRB effectively decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells, but not in hepatocellular carcinoma cells. Contrast to protein levels, cyclin D1 mRNA level did not be changed by MRB treatment. Inhibition of proteasomal degradation by MG132 attenuated MRB-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with MRB. In addition, MRB increased phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine attenuated MRB-mediated cyclin D1 degradation. Inhibition of GSK3ß by LiCl suppressed cyclin D1 phosphorylation and downregulation by MRB. MRB decreased the nuclear level of cyclin D1 and the inhibition of nuclear export by LMB attenuated MRB-mediated cyclin D1 degradation. CONCLUSION: MRB has anti-cancer activity by inducing cyclin D1 proteasomal degradation through cyclin D1 nuclear export via GSK3ß-dependent threonine-286 phosphorylation. These findings suggest that possibly its extract could be used for treating colorectal cancer.


Assuntos
Transporte Ativo do Núcleo Celular , Ciclina D1/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Morus/química , Extratos Vegetais/farmacologia , Treonina/química , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Glicogênio Sintase Quinase 3 beta , Meia-Vida , Humanos , Leupeptinas/farmacologia , Fosforilação/efeitos dos fármacos , Casca de Planta/química , Proteólise/efeitos dos fármacos
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