Research On FoxO1 Mediated Therapy Of Rheumatoid Arthritis By Daemonorops Margaritae Vinum

Background and Objective Rheumatoid arthritis is an autoimmune disease.It is believed that the pathogenesis of this disease is related to various factors such as heredity and environment.Symmetry and polyarthritis are the main clinical manifestations,which can cause joint deformity and disability.Synovial inflammation and vasospasm are the basic pathological changes.At present,rheumatoid arthritis,as one of the world’s most difficult diseases,is a serious threat to human health and a major obstacle to the healthy development of the social economy and health care system.Therefore,it is one of the vital tasks of contemporary biologists,medical scientists and pharmacologists in China to explore the mechanism of RA occurrence and the effective strategies of treatment.However,the specific mechanism of the occurrence of the disease has not been clear yet,there is no ideal specific drug clinically.The therapy of the Western medicine is mainly to control the symptoms of the disease,and drugs are mostly targeted at a single gene as the treatment concept.The clinical control of disease is not satisfactory,becanse the complex pathogenesis of RA.Traditional Chinese medicine has a long history in the treatment of rheumatoid arthritis.It has continuously enriched the experience of drug use on the basis of dialectical treatment,and has the advantage of multi-target intervention.China particularly uses daemonorops margaritae(tripterygium wilfordii)to treat RA in clinical practice at first in the word.It is believed to be the single most positive traditional Chinese medicine for RA treatment.Traditional Chinese medicine believes that wine is the long of all drugs,has the function of clearing collaterals and removing wind,and enhancing the efficacy.Daemonorops margaritae vinum(DMV),a Chinese patent medicine,was developed by honghu hospital of traditional Chinese medicine on the basis of clinical application of tripterygium wilfordii for many years.As a complete root preparation of tripterygium wilfordii,daemonorops margaritae vinum has better clinical treatment effect on RA.Because the pathogenesis of RA is not yet clear,and the mechanism of action of DMV is not clear,the further popularization and application of clinical medication are restricted.Therefore,to further explore the pharmacological molecular mechanism of daemonorops margaritae vinum and elucidate its gene targets is conducive to better guide clinic,and it would be better to provide experimental basis and theoretical basis for finding new biological targets and drug development on RA.Methods Bovine collagen type Ⅱ immune method was adopted to establish the collagen induced arthritis rats model,then we observed the anti-inflammatory effects of the daemonorops margaritae vinum on collagen induced arthritis.On the 14 th day,the situation of models was evaluated,and the CIA rats which were successfully modeled were treated with different doses of DMV.The general condition,weight gain,toe swelling,arthritis index and synovial histopathology of CIA rats were observed in each group.In addition,enzyme linked immunosorbent assay(ELISA)was used to determine the content of serum inflammatory cytokines IL-1β,IL-6 and TNF-alpha,immunohistochemistry was used to determine the phosphorylation levels of nuclear transcription factorkappaκB(NF-κB)and forkhead transcription factor1(FoxO1)in synovial tissue of CIA rats.Results In the study,it was found that the normal group of rats had normal activities,normal diet,bright hair color and no hair loss.Rats in the model group showed signs of hair loss,hypersomnia,lethargy,diet and weight loss,joint redness and tardiness,and even limbs stiffness and crawling.Compared with the model group,the general situation of daemonorops margaritae vinum in each dose group was better than that of the model group after 7 days administration,and the toes swelling degree and arthritis index scores of CIA rat were significantly alleviated(P<0.05,P<0.01.DMV can significantly reduce the degree of inflammatory cell infiltration in the synovial tissue of the knee;it can also significantly down-regulate the expression levels of IL-1β,TNF-αand IL-6 in serum and inhibit the formation of NF-κB,Increase the expression of FoxO1 and inhibit the formation of its phosphorylation(P<0.05,P<0.01).Conclusion Daemonorops margaritae vinum can effectively improve the synovitis infiltration and the symptoms of arthritis in collagen-induced arthritis rats.The mechanism may be related to the inhibition of NF-kB and the formation of pro-inflammatory cytokine IL-1β,TNF-α,and IL-6,as well as the improvement of FoxO1 and its phosphorylation expression.