ABSTRACT
This paper was aimed to study effects of diosgenin on expressions of activator protein-1 (AP-1) and vascular endothelial growth factor (VEGF) in synovial tissues of collagen-induced arthritis (CIA) rats induced by bovine type II collagen, in order to investigate the possible mechanism of herbal medicine diosgenin in the treatment of rheumatoid arthritis (RA). After the CIA rats models were successfully established, rats were randomly divided into the blank control group, CIA model group, diosgenin group, and positive medicine control (tripterygium) group. The in situ hybridization was used to detect the expressions of AP-1 (c-fos and c-jun) in synovial tissues of the knee joint. The real-time PCR was used to detect the VEGF mRNA expression in synovial tissues of rats’ knee joints. The results showed that c-jun and c-fos, VEGF mRNA expressions in synovial tissues of rats’ knee joints were obviously higher than that of the blank control group (P<0.01). After treatment of diosgenin and tripterygium, the expressions of c-jun and c-fos, VEGF mRNA were significantly reduced (P<0.01). It was concluded that diosgenin may regulate the expression of VEGF in synovial tissues through c-jun and c-fos of AP-1 in order to inhibit synovial angiogenesis for the treatment of RA.
ABSTRACT
Objective To study the effects of medicated serum with total saponins from Rhizoma Dioscreae Nipponicae (RDN) on VEGF mRNA expression and AP-1 activity in rat synovial cell strain RSC-364 induced by IL-17 and TNF-α. To investigate the mechanism about total saponin from RDN inhibition of angiogenesis. Methods Medicated serum of total saponins from RDN and tripterygium (positive control) were prepared. Rat synovial cells RSC-364 were divided into four groups: the blank control,IL-17+TNF-α model,tripterygium medicated serum,and total saponins medicated serum groups. After one hour of incubation,all groups except for the blank control were incubated with both IL-17(10 μg·L-1 ) and TNF-α(10 μg·L-1 ) for 24 hours. VEGF mRNA expression in RSC-364 was detected by PrimeScriptTM real-time quantitative PCR (RT-PCR) detection kit,and the AP-1 DNA-binding activity was detected by electrophoretic mobility shift assay (EMSA). Results Compared with the control blank group,both of the VEGF mRNA expression and AP-1 activity in rat synovial cell strain RSC-364 induced by IL-17 and TNF-α increased remarkably (P<0. 05,P<0.01). The VEGF mRNA expression and AP-1 activity in tripterygium medicated serum group and total saponins medicated serum group were remarkably lower than those of the model control group (P<0.05). There was no significant difference between the two medicated serum groups. Conclusion Serum medicated with total saponins from RDN can remarkably decrease VEGF mRNA expression and AP-1 activity,indicating that the total saponins from RDN could influence VEGF secretion by inhibiting the AP-1 signal transduction pathway,VEGF is the key factor of angiogenesis,thereby to restrain angiogenesis.