Format

Send to

Choose Destination
J Pharmacol Exp Ther. 2019 Feb;368(2):218-228. doi: 10.1124/jpet.118.253369. Epub 2018 Dec 10.

Dihydromyricetin Inhibits Inflammation of Fibroblast-Like Synoviocytes through Regulation of Nuclear Factor-κB Signaling in Rats with Collagen-Induced Arthritis.

Author information

1
Departments of Pharmacy (J.W., K.-J.F., B.-X.X., Q.-S.W., T.-Y.W.) and Rheumatology and Immunology (F.-T.Z.), and Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery (T.-T.T.), Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; and Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z.).
2
Departments of Pharmacy (J.W., K.-J.F., B.-X.X., Q.-S.W., T.-Y.W.) and Rheumatology and Immunology (F.-T.Z.), and Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery (T.-T.T.), Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; and Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (J.Z.) drtywang@163.com.

Abstract

Dihydromyricetin (DMY), the main flavonoid of Ampelopsis grossedentata, has potent anti-inflammatory activity. However, the effect of DMY on 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 were then administered DMY intraperitoneally (5, 25, and 50 mg/kg) every other day for 5 weeks. Paw swelling, clinical scoring, and histologic analysis were assessed to determine the therapeutic effects of DMY on the development of arthritis in CIA rats. The results showed that treatment with DMY significantly reduced erythema and swelling in the paws of CIA rats. Pathologic analysis of the knee joints and peripheral blood cytokine assay results confirmed the antiarthritic 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, whereas it significantly increased IL-1β-induced FLS apoptosis in a dose-dependent manner (6.25-25 μM). Moreover, DMY suppressed phosphorylation of IκB kinase (IKK) and inhibitor of NF-κB α and subsequently reduced the IL-1β-induced nucleus translocation of NF-κB in FLSs. Through a 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 demonstrate that DMY could alleviate inflammation in CIA rats and attenuate IL-1β-induced activities in FLSs through suppression of NF-κB signaling.

PMID:
30530730
DOI:
10.1124/jpet.118.253369

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center