Anti-gout Effect And Mechanism Of Shiwuwei Rupeng Pills

Shiwuwei Rupeng Pills?SRP?,Tibet name Albert Qiongjiu Airibu,is described as a famous ancient Tibetan medicine formula for the treatment of joint pain,swelling and joint effusion syndromes.At present,SRP is the preferred drug in Tibetan medicine in the treatment of gouty arthritis,clinical observation of the effect is significant.However,as far as we know,the experimental research of its anti-gout activity is lacked of.In addition,the quality standard of SRP has not been formulated.Therefore,the aim of this study is to systematically studied the quality control and evaluate the therapeutic effects and mechanism of SRP on gout and inflammatory mediators,to provide evidence for its clinical application and promotion.Firstly,mice were injected with Potassium Oxonate(350 mg·kg^-1)to induce hyperuricemia model.After calculating the renal index of mice,it was found that hyperuricmia has no obvious adverse effects on the kidney in a short period of time.In response to SRP and other drugs administration,the level of SUA and SUN decreased significantly.It shows that SRP have obvious effect on reducing uric acid in hyperuricemia.Secondly,the therapeutic effect of SRP and Its components on different inflammatory models was studied by using dimethylbenzene induced ear swelling model and microcrystal sodium urate?MSU?solution induced mouse aerocyst inflammation model.The results showed that SRP can significantly inhibit the ear swelling of mice,reduce the number of white cells in the aerocyst model of mice,and decrease the level of IL-1?and TNF-?in the aerocyst Irrigation Solution.Histopathological staining assay indicated that SRP could inhibit the thickening of aerocyst wall,alleviate the formation of pannus and the inflammatory reaction in the ballon wall.Finally,the model of acute gouty arthritis was induced by injection of MSU solution into articular cavity of the ankle joint,and the behavior of rats was monitored during 1⁴8 hour?s?.The results showed that SRP can significantly improve gait,inhibit articular swelling,enhance the bear weight and enhance the time of thermal hyperalgesia on injected ankles.The histopathological staining assay of the joint tissues indicated that the synovial membrane hyperplasia in the model group was severe,the articular cartilage was eroded to varying degrees,and there are a lot of inflammatory factors in the articular cavity.After adminstration of Colchicine or SRP,the pathological changes of articular can be improved effectively.The ELISA kit was used to detect the inflammatory factors in the rat serum,and the results showed that SRP could significantly reduce the content of IL-1?and TNF-?in the serum of gouty arthritis rats.The protein expression in the synovium of rats was examined by western blot.The results illustrated that after the injection of MSU,the expression of NLRP3,NF-?B,ASC,Caspase-1 and IL-1?was increased,but the expression of Pro-IL-1?was decreased.Compared with the model group,SRP can dose-dependently decrease the expression of Pro-IL-1?,IL-1?,Caspase-1,and so is the Colchicine.According to the result,it can be seen that SRP can inhibit the expression of Pro-IL-1?,IL-1?,Caspase-1 and other proteins,reduce the secretion of inflammatory factory IL-1?and TNF-?,to effectively improve the symptoms of gouty arthritis,and achieve the purpose of treating gout arthritis.Besides,according to the main component of SRP,we establish an HPLC method to analyze the ingredients in SRP,such as aconitine,custunolide and so on,to provide some theoretical basis for the establishment of its quality standard.In summary,the result of this study demonstrated that SRP has hypouricemic effect on oxonate-induced hyperuricemia mice,has anti-inflammatory effect on Dimethylbenzene induced ear swelling,can alleviate MSU-induced gouty arthritis and aerocyst inflammation.The main mechanism may be achieved by improving or inhibiting the inflammatory signaling pathway,which provides a theoretical basis for the clinical application of SRP.