Therapeutic effect of 7, 3'-dimethoxy hesperetin on adjuvant arthritis in rats through inhibiting JAK2-STAT3 signal pathway.
In our previous study, we have demonstrated that 7, 3'-dimethoxy hesperetin (DMHP), an active derivative of hesperidin, showed pro-apoptotic effect on synoviocytes in vitro. The present study was to investigate the potential therapeutic effect of DMHP on adjuvant arthritis (AA) in rat and its possible mechanisms. Freund's complete adjuvant was used to induce AA in rats. DMHP were administered intragastrically once a day from days 12 to 21 after AA induction. Secondary paw swelling, arthritis index, and pathological assessments were observed. IL-6 production in serum and IL-6 mRNA expression in synovium was detected by ELISA and real-time RT-PCR respectively. The expression of mRNA (JAK2, STAT3) and protein (JAK2, p-JAK2, STAT3, p-STAT3) in synovium were determined. We found that DMHP significantly inhibited hind paw swelling and arthritis index, and ameliorated pathological changes of ankle joint in AA rats. DMHP suppressed the level of IL-6 in serum and the expression of IL-6 mRNA in synovium of AA rats in a dose-dependent manner. DMHP apparently decreased mRNA expression of JAK2 and STAT3 as well as protein expression of p-JAK2 and p-STAT3 in the synovium of the AA rats. Correlation analysis indicated that p-JAK2 or p-STAT3 protein expression was highly correlated with joint damage severity. In conclusion, DMHP has a powerful therapeutic effect on AA in rats and its mechanisms might be partly related to inhibiting excessive activation of JAK2-STAT3 pathway.
School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, China.
Rong
R
Li
Li
L
Cai
Dan-yang
DY
Ren
Xue-feng
XF
Xie
Cheng-mu
CM
Hu
Jun
J
Li
D000818:Animals; D000843:Ankle Joint / Q000187:drug effects* / Q000473:pathology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005620:Freund's Adjuvant / Q000276:immunology; D006569:Hesperidin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C570235:hesperetin-7,3'-O-dimethylether; D005620:Freund's Adjuvant; D006569:Hesperidin; C507927:Jak2 protein, rat; D053614:Janus Kinase 2