RESUMEN
The present study aimed to investigate the antiarthritic effect of physcion 8Oßglucopyranoside (POGD) and its possible mechanisms. The antiproliferative effects of POGD on MH7A cells were detected using a CCK8 assay, and the release of proinflammatory cytokines, interleukin (IL)1ß, IL6, IL8, IL12 and IL17A, were determined by ELISA. A type II collageninduced arthritis (CIA) rat model was established to evaluate the antiarthritic effect of POGD in vivo. The paw volumes, arthritis indices and serum levels of tumor necrosis factor (TNF)α, IL1ß, IL6, IL8, IL17A were determined by ELISA. The mRNA expression levels of matrix metalloproteinase (MMP)2, MMP3, MMP9, vascular endothelial growth factor and cyclooxygenase2 were determined by reverse transcriptionquantitative polymerase chain reaction analysis, and the expression levels of transforming growth factor (TGF)ß1, small mothers against decapentaplegic (Smad)4, Smad7, cJun Nterminal kinase (JNK), phosphorylated (p)JNK, pP38, P38, pextracellular signalregulated kinase (ERK)1/2, ERK1/2, nuclear factor (NF)κB p65 in the nucleus (N), cytosolic NFκB p65 (C), and inhibitor of NFκB (IκB) were determined by western blot analysis. The results indicated that POGD significantly inhibited MH7A cell growth. POGD markedly inhibited paw swelling and the arthritis indices of the CIA rats, and POGD may also inhibit the release of proinflammatory cytokines. Furthermore, POGD downregulated the expression levels of TGFß1, Smad4, NFκB p65 (N), p38, pp38, pERK1/2, JNK, pJNK, TGFß1, Smad4, pJNK, JNK, pP38, P38, pERK1/2, ERK1/2 and NFκB p65 (N), and upregulated the Smad7, NFκB p65 (C) and IκB in TNFα induced MH7A cells. In conclusion, the results suggested that POGD is a promising potential antiinflammatory drug, and that POGD may decrease the expression of proinflammatory cytokines and mediators via inhibiting the TGFß/NFκB/mitogenactivated protein kinase pathways.
Asunto(s)
Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Emodina/análogos & derivados , Glucósidos/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Factor de Crecimiento Transformador beta/inmunología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Artritis Experimental/inmunología , Artritis Experimental/patología , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Emodina/química , Emodina/aislamiento & purificación , Emodina/uso terapéutico , Fallopia japonica/química , Femenino , Glucósidos/química , Glucósidos/aislamiento & purificación , Interleucinas/inmunología , Masculino , Ratas , Transducción de Señal/efectos de los fármacos , Sinoviocitos/citología , Sinoviocitos/inmunología , Sinoviocitos/patologíaRESUMEN
This study evaluated the effects of electric pulses combined with antitumor drugs on S180 tumor cells. It was found that the growth of S180 sarcoma was inhibited with a maximum inhibition ratio of 95.5% after the use of electric pulses in combination with the injection of bleomycin (BLM), and the blood vessels of tumor were obviously fewer than those of the untreated tumor in vivo. The mitochondria of S180 tumor cells were swollen after the use of electric pulses in combination with adriamycin. The results showed that electrochemotherapy has evident inhibitory effect on the growth of S180 sarcoma and the mechanism may involve the suppression of tumor angiogenesis and changes in the ultrastructures of tumor cells.