RESUMO
The role of flavonoids of Echinps latifolius (FELT) in Wnt signaling was investigated in adjuvant arthritis (AA) rats. The therapeutic effects of FELT on AA rats were detected by rat arthritis score and MTT. The effect of FELT gavage treatment on the Wnt signaling key gene β-catenin, C-myc and cyclin D1 in synovium from AA rats was detected by Real-time qPCR, and the effects of FELT gavage treatment on the upstream negative regulation gene SFRP 1,2,4,5 in synovium from AA rats were detected by Real-time qPCR. The results showed that FELT gavage treatment significantly inhibited arthritis score and MTT values in AA rats, significantly inhibited the expression of the Wnt signaling gene β-catenin, C-myc and cyclin D1, significantly up-regulated the expression of the up- stream negative regulation gene SFRP 1,2,4. FELT has a better therapeutic effect for AA rats.
Assuntos
Animais , Humanos , Masculino , Ratos , Artrite Experimental , Tratamento Farmacológico , Genética , Metabolismo , Asteraceae , Química , Modelos Animais de Doenças , Regulação para Baixo , Medicamentos de Ervas Chinesas , Flavonoides , Peptídeos e Proteínas de Sinalização Intercelular , Genética , Metabolismo , Proteínas de Membrana , Genética , Metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial , Metabolismo , Via de Sinalização Wnt , beta Catenina , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To investigate the effect of Flavonoids extracted from Echinps latifolius Tausch(FELT) on rheumatoid arthritis (RA) in rat model.</p><p><b>METHOD</b>Fifty SD rats were randomly divided into model group, control group, and low, medium, and high-dose FELT groups (n=10 in each group). Complete Freund's adjuvant (0.1 mL) was used to induce RA in rats. FELT in doses of 50 mg/kg, 100 mg/kg, 150 mg/kg was given to rats in low, medium and high-dose FELT groups by gavage, and same volume of PBS was given to rats in control group. The arthritis score and the paw swelling score were measured to evaluate the therapeutic effect of FELT. Real time qPCR was used to detect the mRNA expression of fibronectin and MMP3 in synovial tissue and the mRNA expression of caspase 3, Bcl-2 and Bcl-2 associated X protein (Bax) in fibroblast-like synoviocytes (FLS).</p><p><b>RESULTS</b>The arthritis score and the paw swelling score were significantly decreased in three FELT groups compared to RA model rats (P <0.05). The relative expression levels of FN and MMP3 mRNA in synovium of three FELT-treatment groups were significantly lower than those in model group (1.80, 1.76 and 1.67 vs 2.53; 1.69, 1.46 and 1.45 vs 2.67, respectively, all P <0.05). The relative expression levels of Bax and caspase 3 mRNA in FLSs of three FELT groups were higher than those in model group (0.56, 0.58 and 0.60 vs 0.30; 0.54, 0.56 and 0.59 vs 0.29, respectively, all P <0.05); while the relative expression levels of Bcl-2 mRNA in FELT groups were lower than that in model group (2.20, 2.08 and 2.08 vs 4.04, respectively, P <0.05).</p><p><b>CONCLUSION</b>FELT may inhibit the synovium proliferation in RA model rats through promoting the FLS apoptosis.</p>
Assuntos
Animais , Ratos , Apoptose , Artrite Reumatoide , Tratamento Farmacológico , Caspase 3 , Metabolismo , Modelos Animais de Doenças , Echinops (Planta) , Química , Fibroblastos , Metabolismo , Flavonoides , Farmacologia , Ratos Sprague-Dawley , Membrana Sinovial , Biologia Celular , Proteína X Associada a bcl-2 , MetabolismoRESUMO
To study the effect of pulchinenoside (PULC) on the Frizzled (FZD) expression of adjuvant arthritis ( AA) rats. AA rats were prepared through the toe injection with complete Freund's adjuvant to culture fibroblast-like synoviocytes (FLS). The effect of the oral administration with PULC on the FZD8 expression was detected by the real time qPCR. The effect of FZD8 knockout on the expressions of IL-1, IL-6, IL-8 were detected by MTT and ELISA. The role of miR-375 in the abnomal expression of FZD8 was detected by the real time qPCR. The results showed signfiicant decrease in the FZD8 expression among AA rats, FLS proliferation ater FZD8 knockout and IL-1, IL-6, IL-8 expressions and notable increase in miR-375 expression after the oral administration with PULC. The up-regulated miR-375 expression can inhibit the FZD8 expression. PULC may inhibit the FZD8 expression by up-regulating the miR-375 expression.
Assuntos
Animais , Humanos , Masculino , Ratos , Artrite Experimental , Tratamento Farmacológico , Genética , Metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Receptores de Superfície Celular , Genética , Metabolismo , SaponinasRESUMO
The role of pulchinenoside (PULC) in the regulation of MeCP2 expression was investigated in RA model rats. Adjuvant arthritis rats were used as RA model rats, and fibroblast-like synoviocytes (FLS) from the RA model rats were cultured. The effect of 100 mg x kg(-1) PULC gavage treatment on the MeCP2 expression and the effect of MeCP2 siRNA on the expression of SFRP2 and β-catenin were detected by real time qPCR and Western blotting. The role of PULC in the FLS proliferation was detected by MTT. The results showed that the MeCP2 expression was down-regulated, the SFRP2 expression was up-regulated and the FLS proliferation was inhibited in FLS after therapy. MeCP2 siRNA significantly inhibited the MeCP2 expression, up-regulated the SFRP2 expression and inhibited the β-catenin expression in FLS from RA model rats. PULC may increase the SFRP2 expression, inhibit the Wnt signaling and inhibit the FLS proliferation in FLS from the RA model rats by inhibiting the MeCP2 expression.