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BACKGROUND: Sepsis is one of the serious disorders in clinical practice. Recent studies found toll-like receptors 4 (TLR4) played an important role in sepsis. In this study, we tried to find the influence of Corilagin on TLR4 signal pathways in vitro and in vivo. METHODS: The cellular and animal models of sepsis were established by LPS and then interfered with Corilagin. Real-time PCR and western blot were employed to detect the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6. ELISA was used to determine the IL-6 and IL-1ß levels in supernatant and serum. RESULTS: The survival rate was improved in the LPS + Corilagin group, and the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6 were significantly decreased than that in the LPS group both in cellular and animal models (P < 0.01). The pro-inflammatory cytokines IL-6 and IL-1ß were greatly decreased in the LPS + Corilagin group both in supernatant and serum (P < 0.01). CONCLUSIONS: Corilagin exerts the anti-inflammatory effects by down-regulating the TLR4 signaling molecules to ameliorate the extreme inflammatory status in sepsis.
Assuntos
Glucosídeos/administração & dosagem , Taninos Hidrolisáveis/administração & dosagem , Sepse/tratamento farmacológico , Receptor 4 Toll-Like/imunologia , Animais , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Células RAW 264.7 , Sepse/genética , Sepse/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genéticaRESUMO
AIM: Radiation-induced brain injury (RIBI) is the most common and severe adverse effect induced by cranial radiation therapy (CRT). In the present study, we examined the effects of the traditional Chinese medicine Shenqi Fuzheng Injection (SFI) on RIBI in mice, and explored the underlying mechanisms. METHODS: C57BL/6J mice were subjected to a single dose of 20-Gy CRT. The mice were treated with SFI (20 mL·kg(-1)·d(-1), ip) for 4 weeks. Morris water maze test was used to assess the cognitive changes. Evans blue leakage and a horseradish peroxidase (HRP) assay were used to evaluate the integrity of the blood-brain barrier (BBB). The expression of inflammatory factors and microglial activation in brain tissues were detected using RT-PCR, Western blotting and immunofluorescence staining. RESULTS: CRT caused marked reductions in the body weight and life span of the mice, and significantly impaired their spatial learning. Furthermore, CRT significantly increased the BBB permeability, number of activated microglia, expression levels of TNF-α and IL-1ß, and the levels of phosphorylated p65 and PIDD-CC (the twice-cleaved fragment of p53-induced protein with a death domain) in the brain tissues. Four-week SFI treatment (administered for 2 weeks before and 2 weeks after CRT) not only significantly improved the physical status, survival, and spatial learning in CRT-treated mice, but also attenuated all the CRT-induced changes in the brain tissues. Four-week SFI pretreatment (administered for 4 weeks before CRT) was less effective. CONCLUSION: Administration of SFI effectively attenuates irradiation-induced brain injury via inhibition of the NF-κB signaling pathway and microglial activation.
Assuntos
Lesões Encefálicas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Medicamentos de Ervas Chinesas/uso terapêutico , NF-kappa B/imunologia , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Encéfalo/imunologia , Encéfalo/patologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/imunologia , Lesões Encefálicas/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Injeções , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos da radiação , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/patologia , Microglia/efeitos da radiação , NF-kappa B/análise , NF-kappa B/antagonistas & inibidores , Lesões por Radiação/etiologia , Lesões por Radiação/imunologia , Lesões por Radiação/patologia , Protetores contra Radiação/administração & dosagem , Transdução de Sinais , Receptor 4 Toll-Like/análise , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologiaRESUMO
[This corrects the article DOI: 10.1093/ecam/neq011.].
RESUMO
Despite the availability of an effective vaccine, the hepatitis B virus (HBV) infection and its treatment remains one of the foremost public health problems in the world. The present study was performed in order to investigate the anti-HBV activity of lutein in vitro. The antiviral activity of lutein was examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNA in stable HBV-producing human hepatoblastoma HepG2 2.2.15 cells. It was found that lutein effectively suppressed the secretion of HBsAg from HepG2 2.2.15 cells in a dose-dependent manner, and it also suppressed the amount of extracellular HBV DNA. A luciferase reporter gene assay was used to determine the effects of lutein on the activities of HBV promoters. The results showed that lutein inhibited the activity of HBV full-length promoter (Fp). These data indicate that lutein possesses an anti-HBV activity and exerts its antivirus effects via inhibition of HBV transcription.
Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Luteína/farmacologia , DNA Viral/análise , Células Hep G2 , Antígenos de Superfície da Hepatite B/análise , Antígenos E da Hepatite B/análise , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacosRESUMO
Melilotus suaveolens Ledeb is a traditional medicinal plant for treating inflammation-related disease. This explores the inner anti-inflammatory mechanism of n-butanol extract from M. suaveolens Ledeb. Inflammatory cellular model was established by lipopolysaccharide intervention on RAW264.7 cell line. Levels of secreted cytokines TNF-α, IL-1ß, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-α, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-κB and ingredients in the extract were assayed by ELISA, real time quantitative PCR, western blot, immunocytochemical test and HPLC fingerprint test, respectively. As a result, the extract could not only markedly reduce the production of pro-inflammatory mediators to different extents by blocking NF-κB activation but also promote the release of anti-inflammatory mediator HO-1 significantly. Each 1 g extract contained 0.023531 mg coumarin and another two high polar ingredients, probably saponins. It can be concluded that the extract has similar effects on antagonizing pro-inflammatory mediators and cytokines like Dexamethasone, and has effects on promoting the production of anti-inflammatory mediators.
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OBJECTIVE: To investigate the therapeutic effects of emodin on acute cholestatic hepatitis and mechanism thereof. METHODS: 96 SD rats were randomly divided into 4 groups to be treated with emodin, ursodeoxycholic acid, dexamethasone, or normal saline respectively for 4 days. On the 5th day gastric perfusion of alpha-naphthylisothiocyanate (ANIT) was performed to establish models of cholestatic hepatitis. 4 - 6 hours after the establishment of model the above mentioned agents were given continuously. 24, 48, and 72 hours after the model establishment blood samples were collected from abdominal aorta to examine the total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), and total bile acid (TBA). Specimen of liver was collected to undergo pathological examination. PCR was used to detect the mRNA expression of cytokine-induced neutrophil chemoattractant 1 (CINC-1) and macrophage inflammatory protein 2(MIP-2), and Western blotting was used to detect the protein expression of intercellular adhesion molecule 1 (ICAM-1). Twenty-four rats treated with NS only were used as controls. RESULTS: The pathological changes of behaviors and liver of the emodin and ursodeoxycholic acid groups were all remarkably milder than those of other model groups. The levels of TB [(32.8 +/- 3.7) micromol/L, (61.0 +/- 16.4) micromol/L, (10.8 +/- 4.5) micromol/L], DB[ (26.03 +/- 3.10) micromol/L, (49.40 +/- 18.16) micromol/L, (8.04 +/- 3.03) micromol/L], and ALT [(314 +/- 50) U/L, (664 +/- 97) U/L, (200 +/- 60) U/L], at the time points 24, 48, and 72 hours, the 48 and 72 hours AST levels, the 48 hours ALP level, the 72 hours GGT level, and the 48 and 72 hours TBA levels of the emodin group were all significantly lower than those of the model group (all P < 0.05). The 24 and 48 hours TB levels, 24 hours DB and ALT, and 24, 72 hours TBA levels of the emodin group were all significantly lower than those of the ursodeoxycholic acid group (all P < 0.05). The 24, 48 hours TB and TBA levels, and the ALT, AST and GGT levels at all time points of the emodin group were all significantly lower than those of the dexamethasone group (all P < 0.05). The CINC-1 and MIP-2 mRNA expression levels and ICAM-1 protein expression levels at all time points of the emodin group were all significantly lower than those of the model group (all P < 0.05). CONCLUSION: Decreasing the levels of TB, DB and ALT in particular, emodin has a protective effect on cholestatic hepatitis. Its effects are quicker than ursodeoxycholic acid, and it has better effects on ALT, AST GGT, and TBA than dexamethasone. These effects may be due to inhibition of the activation of CINC-1, MIP-2, and ICAM-1.
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Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/uso terapêutico , Hepatite/tratamento farmacológico , Fitoterapia , Alanina Transaminase/sangue , Animais , Bilirrubina/sangue , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2 , Colestase/complicações , Modelos Animais de Doenças , Hepatite/etiologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To study the anti-inflammatory effect of petroleum ether extract from Melilotus suaveolens Ledeb. METHODS: Inflammatory cell model was constructed by LPS acting on the RAW264.7 cell line. The expression and distribution of NF-kappaB were detected using immunocytochemical method. The expression of mRNA and protein of Heme oxygenase 1(HO-1) were detected by real-time PCR and Western blot. RESULTS: The immunocytochemical analysis showed that the cytoplasm stained to brown presented NF-kappaB inactivation after the intervention of petroleum ether extract while the cell nucleus stained to brown presented NF-kappaB activation after the only intervention of LPS. The expression of HO-1 mRNA was significantly enhanced by the extract in a dose-dependent manner, and the expression of HO-1 protein was markedly enhanced too. CONCLUSION: The petroleum ether extract from Melilotus suaveolens Ledeb can resist inflammation by inhibiting the activation of proinflammatory factor NF-kappaB and enhancing the expression of anti-inflammatory factor HO-1.
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Anti-Inflamatórios/farmacologia , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Melilotus/química , NF-kappa B/genética , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Éter/química , Heme Oxigenase-1/imunologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/imunologia , Camundongos , NF-kappa B/imunologiaRESUMO
This study is to explore the anti-inflammatory mechanism of the ethanol extract of Duchesnea indica (Andr) Focke. An inflammatory cellular model was established by addition of lipopolysaccharide (LPS) on RAW264.7 cell line. The cellular secretion of TNF-alpha, IL-1beta, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-alpha, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, and activation of NF-kappaB were assayed by ELISA, the Griess method, real-time quantitative PCR, and Western blot and immunocytochemistry method, respectively. The ethanol extract of D. indica not only reduced production of pro-inflammatory cytokines and mediators and blocked NF-kappaB activation, but also slightly promoted release of the anti-inflammatory mediator HO-1 and suppressed IL-10 secretion. In conclusion, the anti-inflammatory effects of the extract of D. indica are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. The extract of D. indica can also slightly promote HO-1 production to reduce inflammation.
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Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , NF-kappa B/metabolismo , Animais , Linhagem Celular , Citocinas/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , CamundongosRESUMO
Corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose) is a novel member of the tannin family which has been discovered from many medicinal plants and has been confirmed in many pharmacological activities. However, the purified Corilagin that was used in experiment is rare, and the anti-inflammatory mechanism of Corilagin has not been investigated clearly. This study is to explore the inner anti-inflammatory mechanism of Corilagin. Inflammatory cellular model was established by lipopolysaccharide (LPS) interfering on RAW264.7 cell line. Levels of TNF-alpha, IL-1beta, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-alpha, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, translocation of NF-kappaB were assayed by ELISA or Griess method, real-time quantitative PCR, western blot and immunocytochemistry method, respectively. As a result, Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone. Corilagin possesses a potential anti-inflammatory effect by not only abating inflammatory impairment but also promoting regression of inflammation and has a good prospect to be used in many inflammation-related diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Glucosídeos/farmacologia , Transporte Ativo do Núcleo Celular , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Heme Oxigenase-1/genética , Taninos Hidrolisáveis , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , RNA Mensageiro/análiseRESUMO
This study is to explore the inner anti-inflammatory mechanism of the ethanol extract of Rungia pectinata (Linn.) Nees. As a result, the ethanol extract of Rungia pectinata (Linn.) Nees could not only strongly reduce production of pro-inflammatory cytokines and mediators via blocking NF-kappaB activation but slightly promote release of anti-inflammatory mediator HO-1 and suppress IL-10 secretion. In conclusion, compared to Dexamethasone, Rungia pectinata (Linn.) Nees has not only similar effects on antagonizing pro-inflammatory mediators and cytokines but also mild effects on promoting production of anti-inflammatory mediators.
Assuntos
Acanthaceae , Anti-Inflamatórios/farmacologia , Citocinas/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Animais , Anti-Inflamatórios/química , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Etanol/química , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Inflamação/imunologia , Interleucina-10/antagonistas & inibidores , Camundongos , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
UNLABELLED: Melilotus suaveolens Ledeb is a species of traditional medical plant for treating inflammation-related disease. This study is to explore the inner anti-inflammatory mechanism on petroleum ether extract from Melilotus suaveolens Ledeb. MATERIALS AND METHODS: Inflammatory cellular model was founded by intervention of lipopolysaccharide (LPS) on RAW264.7 cell line. Secretion of TNF-alpha, IL-1beta, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-alpha, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-kappaB and ingredients in the extract were assayed. RESULTS: The extract could not only reduce production of pro-inflammatory mediators by blocking NF-kappaB activation but promote release of anti-inflammatory mediator HO-1 significantly. The only active ingredient in the extract was coumarin and the concentration of coumarin in each 1 g extract was 0.27822 mg. CONCLUSION: Compared to Dexamethasone, the extract not only has similar effects on antagonizing pro-inflammatory mediators and cytokines but has effects on promoting production of anti-inflammatory mediators.
Assuntos
Alcanos/química , Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Melilotus , Extratos Vegetais/farmacologia , Solventes/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cumarínicos/análise , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dexametasona/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/enzimologia , Macrófagos/metabolismo , Melilotus/química , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , RNA Mensageiro/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To establish a new method for rapidly selecting anti-hepatitis B virus drugs in clinical therapy. METHODS: The full-length hepatitis B virus (HBV) genomes from 8 patients with chronic hepatitis B (CHB) were generated by polymerase chain reaction (PCR). All patients were resistant to lamivudine therapy. Their HBV DNA fragments were inserted into Sap I site of pHY106 eukaryotic expression vector separately. The recombinant plasmids containing 1.1 copies of HBV genome were transfected into Huh7 cell line; the levels of HBsAg, HBeAg and HBV DNA in supernatants of Huh7 cells were measured by ELISA and real-time quantitative PCR, and intracellular HBV replicative intermediates were detected by Southern blot. Antiviral effects of lamivudine and adefovir were evaluated in this vitro system. RESULTS: The 8 recombinant plasmids containing a full-length genome of clinical HBV isolates could replicate and be expressed in Huh 7 cells. There were 6 isolates with polymerase YVDD mutations and 2 isolates with polymerase YIDD mutations. Adefovir, but not lamivudine, inhibited the HBV replication and gene expression in vitro. Furthermore, adefovir inhibited HBV replication in these CHB patients. CONCLUSION: The method described here enables a rapid selection of anti-HBV drugs in clinical therapy and is very useful in antiviral therapy for CHB patients.