RESUMEN
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.
Asunto(s)
Animales , Humanos , Masculino , Ratas , Artritis Experimental , Quimioterapia , Genética , Metabolismo , Asteraceae , Química , Modelos Animales de Enfermedad , Regulación hacia Abajo , Medicamentos Herbarios Chinos , Flavonoides , Péptidos y Proteínas de Señalización Intercelular , Genética , Metabolismo , Proteínas de la Membrana , Genética , Metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Membrana Sinovial , Metabolismo , Vía de Señalización Wnt , beta Catenina , MetabolismoRESUMEN
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.
Asunto(s)
Animales , Humanos , Masculino , Ratas , Artritis Experimental , Quimioterapia , Genética , Metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Receptores de Superficie Celular , Genética , Metabolismo , SaponinasRESUMEN
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.
Asunto(s)
Animales , Humanos , Masculino , Ratas , Artritis Reumatoide , Quimioterapia , Genética , Metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Fibroblastos , Metabolismo , Regulación de la Expresión Génica , Proteína 2 de Unión a Metil-CpG , Genética , Metabolismo , Ratas Sprague-Dawley , Membrana Sinovial , Biología Celular , Metabolismo , Vía de Señalización Wnt , beta Catenina , Genética , MetabolismoRESUMEN
New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.