Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Métodos Terapêuticos e Terapias MTCI
Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Phytomedicine ; 128: 155347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493717

RESUMO

BACKGROUND: Bile acid (BA) enterohepatic circulation disorders are a main feature of chronic cholestatic diseases. Promoting BA metabolism is thus a potential method of improving enterohepatic circulation disorders, and treat enterohepatic inflammation, oxidative stress and fibrosis due to cholestasis. PURPOSE: To investigate the effect of JiaGaSongTang (JGST) and its blood-absorbed ingredient 6-gingerol on α-naphthylisothiocyanate (ANIT)-induced chronic cholestasis, as well as elucidate the underlying regulatory mechanism. METHODS: Chronic cholestasis was induced in mice via subcutaneous injection of ANIT (50 mg/kg) every other day for 14 d. Treatment groups were administered JGST orally daily. Damage to the liver and intestine was observed using histopathological techniques. Biochemical techniques were employed to assess total BA (TBA) levels in the serum, liver, and ileum samples. Liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) was used to analyze fecal BA components. Bioinformatic methods were adopted to screen the core targets and pathways. The blood-absorbed ingredients of JGST were scrutinized via LC-MS/MS. The effects of the major JGST ingredients on farnesoid X receptor (FXR) transactivation were validated using dual luciferase reporter genes. Lastly, the effects of the FXR inhibitor, DY268, on JGST and 6-gingerol pharmacodynamics were observed at the cellular and animal levels. RESULTS: JGST ameliorated pathological impairments in the liver and intestine, diminishing TBA levels in the serum, liver and gut. Fecal BA profiling revealed that JGST enhanced the excretion of toxic BA constituents, including deoxycholic acid. Bioinformatic analyses indicated that JGST engaged in anti-inflammatory mechanisms, attenuating collagen accumulation, and orchestrating BA metabolism via interactions with FXR and other pertinent targets. LC-MS/MS analysis identified six ingredients absorbed to the bloodstream, including 6-gingerol. Surface plasmon resonance (SPR) and dual luciferase reporter gene assays confirmed the abilities of 6-gingerol to bind to FXR and activate its transactivation. Ultimately, in both cellular and animal models, the therapeutic efficacy of JGST and 6-gingerol in chronic cholestasis was attenuated in the presence of FXR inhibitors. CONCLUSION: The findings, for the first time, demonstrated that 6-gingerol, a blood-absorbed ingredient of JGST, can activate FXR to affect BA metabolism, and thereby attenuate ANIT-induced liver and intestinal injury in chronic cholestasis mice model via inhibition of inflammation, oxidative stress, and liver fibrosis, in part in a FXR-dependent mechanism.


Assuntos
1-Naftilisotiocianato , Ácidos e Sais Biliares , Catecóis , Colestase , Álcoois Graxos , Fígado , Receptores Citoplasmáticos e Nucleares , Animais , Ácidos e Sais Biliares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Colestase/tratamento farmacológico , Colestase/metabolismo , Masculino , Camundongos , Catecóis/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Álcoois Graxos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Camundongos Endogâmicos C57BL , Humanos , Doença Crônica , Modelos Animais de Doenças
2.
Phytomedicine ; 20(11): 1039-45, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23746756

RESUMO

PURPOSE: In this study we investigated antinociceptive effects of oxymatrine through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a chronic neuropathic pain model induced by chronic constrictive injury (CCI) of the sciatic nerve. METHODS: The von Frey and plantar tests were performed to assess the degree of mechanical and thermal changes respectively. Immunohistochemistry assay was used to evaluate the expressions of NR2B. Western blotting assay were used to evaluate the expressions of NR2B, tERK, p-ERK, tCREB and p-CREB. RESULTS: The intraperitoneal administration of OMT (160, 80 mg/kg) could prevent the development of mechanical allodynia, thermal hyperalgesia induced by CCI. Intraperitoneal administration of OMT decreased the mean IOD of NR2B in the dorsal horn and expression of NR2B, p-ERK and p-CREB protein. CONCLUSION: Regulation of NMDA NR2B receptor-ERK/CREB signaling maybe the targets for the antinociceptive effects of OMT on a chronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve.


Assuntos
Alcaloides/uso terapêutico , Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Fitoterapia , Quinolizinas/uso terapêutico , Receptores de N-Metil-D-Aspartato/metabolismo , Nervo Isquiático/efeitos dos fármacos , Sophora/química , Alcaloides/farmacologia , Analgésicos/farmacologia , Animais , Dor Crônica/tratamento farmacológico , Dor Crônica/metabolismo , Constrição , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neuralgia/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Quinolizinas/farmacologia , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA