Abstract

Dihydromyricetin (DMY), the main flavonoid of Ampelopsis grossedentata, has a potent anti-inflammation activity. However, the effect of DMY on the chronic autoimmune arthritis remains undefined. In this study we investigated the therapeutic effects of DMY on collagen-induced arthritis (CIA). Wistar rats were immunized with bovine type II collagen to establish CIA and then administered intraperitoneally (i.p.) with DMY (5, 25 and 50 mg/kg) every other day for five weeks. Paw swelling, clinical scoring and histologic analysis were performed to determine the therapeutic effects of DMY on arthritis development in CIA rats. The results showed that treatment with DMY significantly reduced the erythema and swelling in the paws of CIA rats. The pathological analysis of the knee joints and the peripheral blood cytokine assay confirmed the anti-arthritic effects of DMY on synovitis and inflammation. Fibroblast-like synoviocytes (FLSs) were isolated from the synovium of CIA rats and treated with 10 ng/ml interleukin (IL)-1β. DMY significantly inhibited the proliferation, migration and inflammation of IL-1β-induced FLSs, while it significantly increased IL-1β-induced FLSs apoptosis in a dose-dependent manner (6.25-25 μM). Moreover, DMY suppressed the phosphorylation of IκB kinase (IKK) and inhibitor of NF-κB alpha (IκBα), and subsequently reduced IL-1β-induced nucleus translocation of NF-κB in FLSs. Through molecular docking assay we demonstrated that DMY could directly bind to the Thr9 and Asp88 residues in IKKα and the Asp95, Asn142, and Gln167 residues in IKKβ. These findings demonstrated that DMY could alleviate inflammation in CIA rats and attenuate IL-1β-induced activities in FLSs through suppressing the NF-κB signaling.