Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-[kappa]B signaling in macrophages and protecting endothelial cells

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 um...

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Bibliographic Details
Published in:Cell death & disease 2016-09, Vol.7 (9), p.e2350
Main Authors: Han, Qiao, Bing, Wang, Di, Yin, Hua, Li, Shi-he, Li, Yu-hua, Zheng, Xiu-guo, Han, Yu-gang, Wang, Qi-ming, Fan, Shih-mo, Yang, Ting-ting, Tang
Format: Article
Language:English
Subjects:
Arthritis
Cellular biology
Medical screening
Rheumatism
Studies
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Summary: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-B/mitogen-activated protein kinase (NF-B/MAPK) signaling, targeting IB kinase- (IKK) and IKK kinases of macrophages and influencing the expressions of NF-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.
ISSN:2041-4889
DOI:10.1038/cddis.2016.255