Therapeutic Effects Of Gentiopicroside On Adjuvant-induced Arthritis By Inhibiting Inflammation And Oxidative Stress In Rats

Objective:The purpose of this research was to study the effects of each dose of gentiopicroside(GPS)on inflammation and oxidative stress in adjuvant-induced arthritis(AA)rats.The aim of the study was to explore the protective mechanisms of GPS in AA rats and to provide a reference for the development of new drugs for clinical treatment of rheumatoid arthritis(RA).Methods:(1)36 male SD rats were randomly divided into six groups,the Normal group,the model group,GPS groups(low,medium and high dose),the methotrexate(MTX)group.AA rats were induced by intradermal injection of complete Freund's adjuvant(CFA)for 0.1 mL into the right hind paw,except the normal group.After modeling,rats in each group were treated drugs from day 15 to day 26,once a day.The doses in each group were 30,60,90 mg/kg in the GPS groups,and 0.2 mg/kg in the MTX group.The normal group and the model group were intragastrically treated with the same volume of normal saline.(2)Evaluating the anti-inflammatory effect of GPS on AA rats:To explore the effects of GPS on AA rats in the secondary stage of disease.Paw thickness,paw volume and arthritis index of each rat were measured every 3 days.Levels of interleukin(IL)-6,tumor necrosis factor(TNF)-?,IL-1? and IL-17 in plasma were measured by enzyme-linked immunosorbent assay(ELISA),and IL-6,TNF-?,IL-1?,IL-17 mRNA levels in synovial tissues were measured by quantitative real-time polymerase chain reaction(qPCR).X-ray and histopathological examination were detected on Day 26.(3)The antioxidant effects of GPS on AA rats were innovatively studied in this research:Glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),reduced glutathione(GSH),protein carbonyl protein carbonyl(PCO),and malondialdehyde(MDA)levels in plasma were measured as oxidative stress indicators.Results:(1)AA rats were successfully induced by CFA.(2)Anti-inflammation results:Compared with the normal group,the results of each index in the model group were significantly different(P<0.05).Compared with the model group,the results of paw volume,paw thickness and arthritis index decreased significantly(P<0.05);levels of TNF-? and IL-1? in the GPS group decreased significantly(P<0.01);as well as IL-6,TNF-? and IL-1? mRNA levels(P<0.05)in the GPS group.Results of X-ray and histopathological examinations indicated that GPS also has a protective effect on the ankle joints of AA rats.(3)Results of antioxidative activity:Compared with the model group,the results of MDA and PCO levels decreased significantly(P<0.05),and SOD?GSH-Px?GSH levels increased significantly(P<0.05).The results showed that GPS can reduce the levels of lipid oxides and protein oxides by increasing the levels of antioxidants and antioxidant enzymes,to achieve anti-oxidative effects.Conclusion:Therapeutic effects of GPS on AA by inhibiting inflammation and oxidative stress in rats.