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1.
J Agric Food Chem ; 68(1): 160-167, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31825618

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of intestinal mucosa and submucosa, characterized by the disruption of the intestinal epithelial barrier, increased production of inflammatory mediators, and excessive tissue injury. Intestinal epithelial cells, as well as microvascular endothelial cells, play important roles in IBD. To study the potential effects of kaempferol in IBD progress, we established a novel epithelial-endothelial cells coculture model to investigate the intestinal inflammation and barrier function. Data demonstrated an obvious increased transepithelial electrical resistance (TEER) (1222 ± 60.40 Ω cm2 vs 1371 ± 38.77 Ω cm2), decreased flux of FITC (180.8 ± 20.06 µg/mL vs 136.7 ± 14.78 µg/mL), and up-regulated occludin and claudin-2 expression in Caco-2 that was specifically cocultured with endothelial cells. Meanwhile, 80 µM kaempferol alleviated the drop of TEER, the increase of FITC flux, and the overexpression of interleukin-8 (IL-8) induced by 1 µg/mL lipopolysaccharide (LPS). Additionally, kaempferol also ameliorated the LPS-induced decrease of protein expression of zonula occludens-1 (ZO-1), occludin, and claudin-2, together with the inhibited protein expressions of the phosphorylation level of NF-κB and I-κB induced by LPS. Our results suggest that kaempferol alleviates the IL-8 secretion and barrier dysfunction of the Caco-2 monolayer in the LPS-induced epithelial-endothelial coculture model via inhibiting the NF-κB signaling pathway activation.


Assuntos
Células Endoteliais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/citologia , Quempferóis/farmacologia , Lipopolissacarídeos/efeitos adversos , Células CACO-2 , Claudina-2/genética , Claudina-2/metabolismo , Técnicas de Cocultura , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/imunologia , Microvilosidades/efeitos dos fármacos , Microvilosidades/genética , Microvilosidades/metabolismo , Ocludina/genética , Ocludina/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
2.
J Agric Food Chem ; 68(1): 168-175, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31850758

RESUMO

Naringin is a polymethoxylated flavonoid commonly found in citrus species and has therapeutic potential in intestinal disorders. However, the effect and mechanism of naringin on gut-vascular barrier disruption has not yet been reported. This study aimed to investigate the distinguishing and selectively protective effects of naringin on tumor necrosis factor (TNF)-α-induced gut-vascular barrier disruption and elucidate the potential mechanism. In the present study, an in vitro gut-vascular barrier model composed of rat intestinal microvascular endothelial cells (RIMVECs) was studied. Evans blue-albumin efflux assay showed that naringin (50 µM) evidently protected the integrity of RIMVEC monolayer barriers against TNF-α-induced disruption. Naringin maintained the expression and distribution of tight junction proteins including zona occludin-1, occludin, claudin-1, and claudin-2. Additionally, naringin protected RIMVECs from TNF-α-induced apoptosis and cell migration suppression (41.1 ± 2.2 vs 51.1 ± 3.5%; 61.0 ± 5.1 vs 72.2 ± 6.2%). Our results indicate that naringin effectively ameliorates gut-vascular barrier disruption.


Assuntos
Células Endoteliais/efeitos dos fármacos , Flavanonas/farmacologia , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Apoptose/efeitos dos fármacos , Citrus/química , Claudina-1/genética , Claudina-1/metabolismo , Células Endoteliais/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Microvasos/citologia , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Ocludina/genética , Ocludina/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética
3.
Mol Med Rep ; 19(3): 1958-1964, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30569099

RESUMO

Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory disease of the small and/or large intestine. Endothelial expression of inflammatory mediators, including cytokines and adhesion molecules, serves a critical role in the initiation and progression of IBD. The dietary flavonoid, kaempferol, has been reported to inhibit expression of inflammatory mediators; however, the underlying mechanisms require further investigation. In the present study, a novel molecular mechanism of kaempferol against IBD was identified. The potential anti­inflammatory effect of kaempferol in a cellular model of intestinal inflammation was assessed using lipopolysaccharide (LPS)­induced rat intestinal microvascular endothelial cells (RIMVECs), and an underlying key molecular mechanism was identified. RIMVECs were pretreated with kaempferol of various concentrations (12.5, 25 and 50 µM) followed by LPS (10 µg/ml) stimulation. ELISA was used to examine the protein levels of tumor necrosis factor­α (TNF­α), interleukin­1ß (IL­1ß), IL­6, intercellular adhesion molecule-1 (ICAM­1) and vascular cell adhesion molecule-1 (VCAM­1) in the supernatant. Protein expression levels of Toll­like receptor 4 (TLR4), nuclear factor­κB (NF­κB) p65, inhibitor of NF­κB, mitogen­activated protein kinase p38 and signal transducer and activator of transcription (STAT) in cells were measured by western blotting. Kaempferol significantly reduced the overproduction of TNF­α, IL­1ß, interleukin­6, ICAM­1 and VCAM­1 induced by LPS, indicating the negative regulation of kaempferol in TLR4, NF­κB and STAT signaling underlying intestinal inflammation. The present results provide support for the potential use of kaempferol as an effective therapeutic agent for IBD treatment.


Assuntos
Mediadores da Inflamação/administração & dosagem , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Quempferóis/administração & dosagem , Animais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Molécula 1 de Adesão Intercelular/genética , Interleucina-1beta/genética , Interleucina-6/genética , Intestinos/efeitos dos fármacos , Intestinos/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Molécula 1 de Adesão de Célula Vascular/genética
4.
Life Sci ; 216: 168-175, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30471284

RESUMO

AIMS: In this study, we explored the underlying mechanisms of protective effects of rhein against intestinal barrier injury in a rat model, induced by intraperitoneal injection of lipopolysaccharide (LPS). MAIN METHODS: Twenty-four male rats were assigned equally to three groups. Rats were given an oral administration of rhein (66.7 mg/kg/day) or not for three continuous days. LPS or saline were injected intraperitoneally in an hour after the last oral administration. The rats were sacrificed at 7 h after LPS or saline administration. Both blood samples and intestinal samples were collected. KEY FINDINGS: Rhein pretreatment markedly inhibited the levels of serum diamine oxidase (DAO), D-lactate (D-lac) and intestinal histological damage, significantly recovered the levels of intestinal DAO, ZO-1 and occludin. Additionally, rhein suppressed LPS-induced intestinal inflammation and oxidative stress, by decreased serum and intestinal, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and nitric oxide levels, up-regulated intestinal catalase, glutathione peroxidase (GSH-Px) activities and HO-1 expression, and down-regulated malondialdehyde (MDA) level in the small intestine. Finally, rhein inhibited JNK, p38 MAPK phosphorylation and activated Nrf2 pathway. SIGNIFICANCE: Rhein could exert the anti-inflammatory and anti-oxidative effects against LPS-induced intestinal barrier injury by suppressing p38 MAPK and JNK and activating Nrf2 pathway.


Assuntos
Antraquinonas/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Inflamação/patologia , Interleucina-1beta/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Molecules ; 23(9)2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201908

RESUMO

Tetrahydroxystilbene glucoside (TSG) is a unique component of the bone-reinforcing herb Radix Polygoni Multiflori Preparata (RPMP). It has the ability to promote bone formation and protect osteoblasts. However, the underlying mechanism remains unclear. To better understand its biological function, we determined TSG's effect on murine pre-osteoblastic MC3T3-E1 cells by the MTT assay, flow cytometry, FQ-PCR, Western blot, and ELISA. The results showed that TSG caused an elevation of the MC3T3-E1 cell number, the number of cells in the S phase, and the mRNA levels of the runt-related transcription factor-2 (Runx2), osterix (Osx), and collagen type I α1 (Col1a1). In addition, the osteoprotegerin (OPG) mRNA level was up-regulated, while the nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) mRNA levels were down-regulated by TSG. Furthermore, TSG activated the phosphoinosmde-3-kinase/protein kinase B (also known as PI3K/Akt) pathway, and blocking this pathway by the inhibitor LY-294002 could impair TSG's functions in relation to the MC3T3-E1 cells. In conclusion, TSG could activate the PI3K/Akt pathway and thus promote MC3T3-E1 cell proliferation and differentiation, and influence OPG/RANKL/M-CSF expression. TSG merits further investigation as a potential therapeutic agent for osteoporosis treatment.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Glucosídeos/farmacologia , Fator Estimulador de Colônias de Macrófagos/genética , Osteoprotegerina/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/genética , Estilbenos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Glucosídeos/química , Fator Estimulador de Colônias de Macrófagos/metabolismo , Camundongos , Morfolinas/farmacologia , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estilbenos/química , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
6.
Nanotechnology ; 29(48): 485601, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30215618

RESUMO

We demonstrate surfactant- and template-free synthesis of superhydrophobic thin films by controlling surface morphology. The surface morphology evolution process was determined from time-dependent studies. The relationships between the water contact angle, sliding angle, water droplet size, and surface microstructures were investigated. It is found that structural parameters play an important role in determining the adhesion of a droplet on superhydrophobic surfaces and the liquid-solid adhesion can be effectively manipulated through tailoring the morphology or the size of the microstructures on the surface. We provide a theoretical explanation for the Cassie-Baxter state (water rolls) and the Wenzel state (sticky surface, water adheres) with droplet size on different microstructure surfaces. The new theoretical insight provided in this study matches well with experimental results.

7.
Dig Dis Sci ; 63(12): 3297-3304, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30076503

RESUMO

BACKGROUND: In inflammatory bowel disease, activation of microvascular endothelial cells and adhesion of immune cells are required for the initiation and maintenance of inflammation. We evaluated the effects and mechanisms of quercetin, a flavone identified in a wide variety of dietary sources, in LPS-induced rat intestinal microvascular endothelial cells (RIMVECs). METHODS: RIMVECs were pretreated with quercetin of various concentrations (20, 40 and 80 µM) followed by LPS (10 µg/ml) stimulation. ELISA was used to examine protein levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatant. Protein levels of Toll-like receptor 4 (TLR4), nuclear transcription factor kappa B (NF-κB) p65, inhibitors of NF-κB (IκB-α), extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK) p38 and signal transducer and activator of transcription (STAT) in cells were measured by Western blot. RESULTS: Quercetin significantly suppressed protein levels of ICAM-1 and VCAM-1 induced by LPS. Quercetin also inhibited TLR4 expression, NF-κB p65, ERK, JNK and STAT phosphorylation and decreased IκB-α degradation. Moreover, the MAPK p38 signal does not contribute to the anti-inflammatory effects on RIMVECs, although LPS significantly increases its phosphorylation. CONCLUSIONS: These results indicate that quercetin may have an anti-inflammatory effect by inhibiting expression of ICAM-1 and VCAM-1 in RIMVECs by suppressing TLR4, NF-κB, ERK, JNK and STAT but not the p38 signaling pathway.


Assuntos
Células Endoteliais , Doenças Inflamatórias Intestinais , Quercetina/farmacologia , Transdução de Sinais , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Células Endoteliais/fisiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Intestinos/fisiologia , NF-kappa B/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/metabolismo , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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