RESUMO
BACKGROUND: Estrogen receptor ß (ERß) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERß. Here, we explore the effect of overexpressed ERß on human HSCs and the role of ERß in pharmacological action of calycosin. METHODS: LX-2 cells were transfected with lentivirus to overexpress ERß. In the presence or absence of overexpressed ERß, the effects of ERß and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-ß1-induced LX-2 cells and the role of ERß in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERß or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERß on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot. RESULTS: ERß overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERß or calycosin alone inhibited the TGF-ß1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERß and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERß overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed. CONCLUSIONS: ERß mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect.
Assuntos
Receptor beta de Estrogênio , Células Estreladas do Fígado , Proliferação de Células , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Receptor beta de Estrogênio/uso terapêutico , Fibrose , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Isoflavonas , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/farmacologia , Metaloproteinase 1 da Matriz/uso terapêutico , Fosforilação , Fitoestrógenos/farmacologia , Fator de Transcrição STAT3 , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/uso terapêuticoRESUMO
Ginkgo biloba extract (GBE) is a plant extract obtained from the leaves of G biloba tree. The aim of this study was to evaluate the clinicopathologic characteristics and therapeutic effects of GBE on ischemic colitis (IC).Forty-seven patients with IC were divided as GBE group (nâ=â30) and routine group (nâ=â17). The routine group was given routine therapy, and the GBE group was given routine therapies plus GBE intravenous injection. Clinicopathologic characteristics, endoscopy findings, serum antioxidant enzymes, and inflammatory mediators were evaluated.About 89.3% initial symptom was acute-onset abdominal cramping and abdominal pain followed with hematochezia. The lesions were mainly located in sigmoid colon (80.8%). Serum level of superoxide dismutase (SOD) in patients with IC was significantly decreased (Pâ<â.05), while methane dicarboxylic aldehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels were significantly increased (Pâ<â.05). However, serum procalcitonin (PCT) level showed no significant change. Treatment of GBE resulted in quick remittance of abdominal pain and hematochezia, and significant attenuation of colon macroscopic and histologic damage in all patients. Furthermore, the treatment also significantly increased SOD levels, decreased MDA, TNF-α, and IL-6 levels (Pâ<â.05).Acute-onset abdominal cramping or abdominal pain followed with hematochezia was the mainly initial symptom of IC, and sigmoid and descending colons were the common vulnerable sites. GBE exerted a beneficial effect on IC with faster symptom relief and better mucosal healing, possibly through scavenging oxidative-free radicals and downregulating inflammatory mediators. GBE may be a promising candidate for protection against IC.
Assuntos
Colite Isquêmica/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Doença Aguda , Idoso , Antioxidantes/análise , Colite Isquêmica/sangue , Feminino , Ginkgo biloba , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Oxidative stress could be a major contributing factor to the tissue injury that characterize inflammatory bowel disease (IBD). Homocysteine (HCY) could cause oxidative damage to the colon tissue in ulcerative colitis (UC) patients, melatonin (MLT) supplementation could reduce oxidative damage that caused by HCY in vitro and in vivo. In this study, we aimed to determine the levels of plasma HCY and MLT simultaneously in UC patients. METHODS: Collected the clinical data of 112 UC patients and 110 healthy controls (HC). The levels of plasma HCY and MLT were detected by HPLC-FD method. The levels of plasma folate, vitamin B(12) (VitB(12)) were detected by ELISA method. RESULTS: The levels of plasma HCY in UC patients were significantly higher than that in HC (11.27±7.26 µmol/L vs. 8.19±4.81 µmol/L, P=0.000). The levels of plasma MLT in UC patients were significantly lower than that in HC (49.06±31.40 pg/ml vs. 64.28±41.16 pg/ml, P=0.008). The levels of plasma folate and VitB(12) in UC patients were lower than that in HC (7.64±1.95 nmol/L vs. 9.14±1.23 nmol/L, 108.64±32.22 pmol/L vs. 112.64±33.33 pmol/L, P<0.05). The levels of plasma HCY and MLT in UC patients were not correlated with either the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) or the disease activity, localization and duration of UC (P>0.05). The change of increasing levels of plasma MLT but decreasing levels of plasma HCY was shown in UC patients, however, the association between the levels of plasma MLT and HCY were not statistically significant (P>0.05). CONCLUSIONS: The levels of plasma HCY were increased whereas the levels of plasma MLT were decreased in UC patients.