Guishao Zhimu Decoction alleviates inflammatory response in rheumatoid arthritis rats via inhibiting cGAS-STING-NFκB axis
Objective It is to investigate the effect and mechanism of Guishao Zhimu Decoction(GSZD)on inflamma-tory activity in rheumatoid arthritis rats via inhibiting cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)-nuclear factor kappa-B(NF-κB)axis.Methods Seventy Wistar rats were taken,in which 10 rats were randomly selected as the normal group,and the remaining 60 rats were prepared to establish models of collagen-induced arthritis.The successfully modeled rats were randomly divided into model group,methotrexate(MTX)group,tripterysium glycosides(TG)group and low,medium and high dose groups of GSZD,with 10 rats in each group.The MTX group was given 0.104 mg/mL MTX tablet suspension by gavage once per week,and given distilled water by gavage once per day for the rest of the week;the TG group was given 0.625 mg/mL TG tablet suspension by gavage,and the low,medium,and high dosage groups of GSZD were respectively given 0.958 g/mL,1.916 g/mL,and 2.874 g/mL GSZD by gavage,and the normal group and model group were given distilled water by gavage,all once daily.All the groups were treated for 4 weeks.The degree of toe swelling of rats in each group was measured after 1,2,3,and 4 weeks of treatment,and the arthritis index(AI)was cal-culated;at the end of the final intervention,the serum levels of interleukin-1β(IL-1β),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected by ELISA,and the expressions of cGAS,STING,NF-κB p65,and IκBα proteins in synovial tissue were detected by Western blot.Results At the end of 1,2,3 and 4 weekends of the interven-tion,the joint swelling of rats of the model group was significantly higher than that of the normal group(all P<0.05);with the increase in time,the joint swelling of rats in the model group were gradually increased,and that of rats in every treatment group were decreased to different degrees,the joint swelling of GSZD medium dose group was significantly lower than that of the model group at the end of 4 weekends of the intervention(P<0.05).At the end of one week of interven-tion,the differences in AI scores among each group were not statistically significant(all P>0.05);at the end of 2,3,and 4 weeks of intervention,the AI scores of the GSZD high-dose group were significantly lower than those of the model group and GSZD low-dose group(all P<0.05),and the AI scores of the GSZD high-dose group were significantly lower than those of the TG group at the end of 2 weeks of intervention(all P<0.05);at the end of 3 weeks of intervention,the AI scores of the MTX group and the GSZD medium-dose group were significantly lower than those of the model group(all P<0.05);at the end of 4 weeks of intervention,the AI scores of the MTX group,GSZD medium-dose group and GSZD low-dose group were all significantly lower than those of the model group(all P<0.05).Compared with the normal group,the serum levels of IL-1β,IL-17,TNF-α and relative expressions of cGAS,STING and NF-κB p65 proteins in synovial tissues of the model group were significantly increased(all P<0.05),and the relative expression of IκBα protein in synovial tis-sues was significantly decreased(P<0.05);compared with the model group,the serum levels of IL-1β,IL-17 and TNF-α and relative expressions of cGAS,STING,NF-κB p65 proteins in synovial tissues of each treatment group were signifi-cantly reduced(all P<0.05),and relative expression of IκBα protein in synovial tissues was significantly increased(all P<0.05).The serum levels of IL-1β,IL-17 and TNF-α and relative expressions of cGAS,STING,NF-κB p65 proteins in synovial tissues of the MTX group and GSZD high dose group were significantly lower,while the relative expression of IκBα protein in synovial tissues was significantly higher than those of the GSZD low dose group(all P<0.05).Conclusion Guishao Zhimu Decoction can significantly alleviate joint swelling and joint inflammation in rats with rheumatoid arthritis,and the mechanism may be related to inhibit cGAS/STING/NF-κB pathway,thus to reduce the levels of inflammatory factors.
Guishao Zhimu Decoctionrheumatoid arthritiscGAS/STING/NF-κB pathwayarthritis index
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