RESUMO
The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction (HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2R proteins were established using the homology modelling (HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.
Assuntos
Humanos , Anti-Inflamatórios não Esteroides , Farmacocinética , Berberina , Farmacocinética , Dinoprostona , Medicamentos de Ervas Chinesas , Química , Farmacocinética , Células KB , Glicoproteínas da Membrana de Plaquetas , Transporte Proteico , Receptores Acoplados a Proteínas G , Receptores de Tromboxano A2 e Prostaglandina H2 , Sepse , Tratamento Farmacológico , Metabolismo , Acetato de Tetradecanoilforbol , FarmacocinéticaRESUMO
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 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
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.
Assuntos
Animais , Humanos , Masculino , Ratos , Artrite Reumatoide , Tratamento Farmacológico , Genética , Metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibroblastos , Metabolismo , Regulação da Expressão Gênica , Proteína 2 de Ligação a Metil-CpG , Genética , Metabolismo , Ratos Sprague-Dawley , Membrana Sinovial , Biologia Celular , Metabolismo , Via de Sinalização Wnt , beta Catenina , Genética , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To observe the effect of cyclovirobuxinum-D (CVB-D) on cerebral ischemia-reperfusion injury in rats and explore its mechanisms.</p><p><b>METHOD</b>One hundred and twenty rats were randomly divided into three CVB-D groups (2, 1, 0.5 mg x kg(-1)), Nimodipine group (2 mg x kg(-1)), model group and sham operated group, 20 rats each group. Rat cerebral ischemia-reperfusion injury model was induced by middle cerebral artery occlusion, the nerve injury symptoms was evaluated, the level of SOD and MDA in brain tissue were determined, the concentration of intracellar Ca2+ of brain was measured, and the pathological change of brain was also observed.</p><p><b>RESULT</b>CVB-D could improve the nerve injury symptoms, reduce the infarction area of brain, the concentration of intracellar Ca2+ and the level of MDA, increase the activity of SOD, and decrease the pathological change of brain.</p><p><b>CONCLUSION</b>CVB-D has protective effect on cerebral ischemia-reperfusion injury in rats.</p>