| Objective: Under the guidance of modern pharmacology theory, the aim of this studywas to investigate the therapeutic effect and the mechanism of Geniposide (GE) onadjuvant arthritis (AA) rats, explore the impact of GE on Th17-related characteristiccytokines of peripheral blood lymphocytes (PBL) suspension in AA rats, and researchthe effect of GE on c-Jun N-terminal kinase (JNK) signal transduction pathway and thelevel of cytokines of PBL in AA rats.Methods: Experimental animal models were designed according to the characteristicsof rheumatoid arthritis (RA). Rats were immuned by injecting with Freund’s completeadjuvant (FCA) to develop AA rat model. The rats with AA were given intragastricallyJA (30,60,120mg kg1day1) from day18to24after immunization. Paw swelling andarthritis score was observed for each group of rats. MTT assay was used to detect theinhibition of GE on the proliferation of PBL through in vitro cell culture experiments.IL-6, IL-17, IL-23, TGF-β1and IFN-γ were determined by enzyme-linkedimmunosorbent assay (ELISA). The phosphorylation of JNK was detected by westernblot (WB).Results: Normal rats after inflammation were given different doses of GE for sevendays and each group could significantly inhibit the AA rat paw swelling and arthritisindex. By isolating rat PBL cells in vitro cultivation, we found that the reaction of GEand PBL arrive at the optimal inhibition effect at3h. ELISA experimental results showthat: The low-dose and medium-dose of GE could down-regulate pro-inflammatorycytokines IL-17and IL-23levels of PBL in AA rats, while raising the level of theanti-inflammatory cytokine TGF-β1(P <0.05or P <0.01) of PBL in AA rats. All groupsdecreased IL-6levels (P <0.05or P <0.01) of PBL in AA rats. The level of IFN-γ was nosignificant change (P>0.05) of PBL in AA rats. The WB method experimental results show that: each administration group could inhibit the phosphorylation of JNKsignaling pathway (P <0.05or P <0.01), and play an important role in blocking JNKsignaling pathway and slowing inflammation.Conclusion: The above results show that: GE could significantly inhibit the AA rat pawswelling and arthritis index; GE could reverse the imbalance of various cytokines byincreasing the level of anti-inflammatory cytokines and decreasing the level ofpro-inflammatory cytokines. GE could reduce the hyper-phosphorylation of JNK signalpathway of PBL in the AA rats, down-regulate the expression of p-JNK, inhibit theactivity of the JNK pathway and suppress the immune response, so as to achieve thepurpose of treatment of RA. |
PDF Full Text Request