5,7,3′-Triacetyl Hesperetin Suppresses Adjuvant-Induced Arthritis in Rats through Modulating JAK2/STAT3 Pathway

Abstract

This work was designed to identify the effect of 5,7,3'-triacetyl hesperetin (TAHP) on rat adjuvant arthritis (AA) and further clarify the possible role of TAHP on modulating Janus kinase signal transducers and activators (JAK/STAT in this process. Freund's complete adjuvant was used to induce AA in rats. TAHP (33, 66, 132 mg/kg) was administered intragastrically. Secondary paw swelling, polyarthritis index, index of immune organs and histopathological assessment were used to evaluate the effects of TAHP on AA in rats. IL-6 in serum and in synovial tissues was examined with ELISA and RT-PCR. In addition, JAK2/STAT3 pathway-related key molecules mRNA expression in synovial tissues of AA rats were detected by RT-PCR and western blot respectively. It was found that TAHP (66, 132 mg/kg) could significantly inhibit secondary paw swelling, restore the index of immune organs and reduce polyarthritis index. Results of histopathological assessment showed that TAHP clearly ameliorated the pathological changes in AA rats. TAHP could downregulate the level of IL-6 in serum and in synovial tissues of AA rats. Besides, treatment with TAHP could decrease mRNA expressions of STAT3 and JAK2, as well as the ratio of p-JAK2/JAK2 protein and p-STAT3/STAT3 protein from synovial tissues. Thus, the paper demonstrated that TAHP had a therapeutic effect on AA in rats and the mechanisms were partly associated with modulating proinflammatory cytokine IL-6 production in serum and in synovial tissues and inhibiting excessive activation of JAK2/STAT3 signaling pathway which might play a crucial role in the pathogenesis of AA.

Fucoidan Isolated from Saccharina japonica Inhibits LPS-Induced Inflammation in Macrophages via Blocking NF-κB, MAPK and JAK-STAT Pathways

“…Upon inflammatory activation, membrane bound JAK receptor proteins enhance the phosphorylation of the major substrate, the family of STATs, including STAT1 and STAT3. Phosphorylated STAT1/3 can translocate to the nuclear and then result in the expression of pro-inflammatory genes [47][48][49]. In this study, SF6 treatment could significantly down-regulate JAK2 phosphorylation and nuclear translocation of STAT 1/3, indicating that SF6 could prevent the activation of JAK2 and then inhibit JAK2-STAT1/3 pathway.…”

Tetrahydroxystilbene Glucoside Improves TNF-α-Induced Endothelial Dysfunction: Involvement of TGFβ/Smad Pathway and Inhibition of Vimentin Expression

“…Afterwards, the proteins were separated by 12% SDS-polyacrylamide gel electrophoresis (PAGE) and transferred onto polyvinylidene difluoride (PVDF) membranes. Membranes were blocked with 5% nonfat milk in TBS (pH 7.4) with 0.1% Tween-20 for 1 h at room temperature and then incubated overnight at 4 C with different primary antibodies (Ren et al, 2013). The signals were detected by HRP-conjugated secondary antibodies for 1 h at room temperature on an ECL detection system (Amersham Biosciences).…”

Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways

“…NF-κB, as a transcription factor, plays a vital role in regulating the immune response to infection by controlling inflammatory gene expression and cytokine production [ 3 – 5 ]. Jak-Stat pathways have been reported to be involved in microglia-mediated inflammation responses induced by LPS and endogenous production of interferon (IFN)-γ and IL-6 [ 6 – 7 ].…”