文献类型：期刊文献

英文题名：Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells

作者：Qiao Han[1];Wang Bing[2];Yin Di[3];Li Hua[2];Li Shi-he[2];Zheng Yu-hua[4];Han Xiu-guo[1];Wang Yu-gang[1];Fan Qi-ming[1];Yang Shih-mo[3];Tang Ting-ting[1]

机构：[1]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Shanghai Key Lab Orthopaed Implants,Sch Med, Shanghai, Peoples R China;[2]Kunming Med Univ, Affiliated Hosp 1, Dept Orthopaed Surg, Kunming, Peoples R China;[3]East China Univ Sci & Technol, Complex & Intelligent Res Ctr, Sch Mech & Power Engn, Shanghai, Peoples R China;[4]Wenshan Zhengbao Orthopaed Hosp Yunnan Prov, Wenshan, Peoples R China

年份：2016

卷号：7

外文期刊名：CELL DEATH & DISEASE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000382326800008)】；

基金：This work was supported by the National Natural Science Foundation of China (81172549 and 81672205).

语种：英文

摘要：Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-kappa B/mitogen-activated protein kinase (NF-kappa B/MAPK) signaling, targeting I kappa B kinase-alpha (IKK alpha) and IKK beta kinases of macrophages and influencing the expressions of NF-kappa B downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically.