[Cheng's Juanbi Decoction alleviates the inflammation in collagen-induced arthritis (CIA) rats via inhibiting activation of PI3K/AKT/mTOR pathway].

Objective To investigate the potential mechanism of Cheng's Juanbi Decoction (JBT) for treating collagen-induced arthritis (CIA) in rats. Methods Female SD rats were divided into normal group, CIA model group, methotrexate (MTX) group, JBT group with different doses, and LY294002 (PI3K blocker) group. The effects of JBT on toe swelling and arthritis index of rats before and after treatment were evaluated. HE staining was used to observe the pathological changes of synovial tissues. ELISA was used to determine the levels of interleukin-1β (IL-1β) and tumor necrosis factor α(TNF-α) in synovium of rats. Real-time quantitative PCR was used to detect mRNA expression levels of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), beclin-1, and P62. The expressions of AKT, phosphorylated AKT (p-AKT), mTOR, phosphorylated mTOR (p-mTOR), PI3K, phosphorylated PI3K (p-PI3K), P62, beclin-1, and microtubule-associated protein 1 light chain 3B (LC3B) were detected by Western blot analysis. Results Compared with the normal group, the toe of other groups was significantly swollen 1 hour before administration. Compared with the conditions 1 hour before administration, toe swelling in the high-dose JBT group, MTX group, and LY294002 group was significantly relieved 2 hours before blood collection after 30 days of administration. JBT can significantly reduce the degree of toe swelling, arthritis index(AI) score, and the destruction of synovial tissue. The levels of IL-1β, TNF-α, mRNA expression of PI3K, AKT, mTOR and P62, and protein levels of p-PI3K, p-AKT, p-mTOR, and P62 in synovium samples of rats in the high-dose JBT group were significantly decreased. Beclin-1 mRNA and protein expression and LC3B protein level were significantly increased. Conclusion JBT may alleviate joint inflammation by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway, and the therapeutic effect of high-dose JBT is comparable to that of MTX and LY294002.