title: Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells.
abstract: 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-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α (IKKα) and IKKβ kinases of macrophages and influencing the expressions of NF-κB 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.
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Qiao
authors: Q
authors: Han
authors: Department of Orthopaedic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors: Wang
authors: W
authors: Bing
authors: Complex and Intelligent Research Center, School of Mechanical and Power Engineering, East China University of Science and Technology, Shanghai, People's Republic of China.
authors: Yin
authors: Y
authors: Di
authors: Department of Orthopaedic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors: Li
authors: L
authors: Hua
authors: Department of Orthopaedic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors: Li
authors: L
authors: Shi-He
authors: Wenshan Zhengbao Orthopaedic Hospital of Yunnan Province, Wenshan, People's Republic of China.
authors: Zheng
authors: Z
authors: Yu-Hua
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Han
authors: H
authors: Xiu-Guo
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Wang
authors: W
authors: Yu-Gang
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Fan
authors: F
authors: Qi-Ming
authors: Complex and Intelligent Research Center, School of Mechanical and Power Engineering, East China University of Science and Technology, Shanghai, People's Republic of China.
authors: Yang
authors: Y
authors: Shih-Mo
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Tang
authors: T
authors: Ting-Ting
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015210:Arthritis, Gouty / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003460:Crystallization; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005121:Extremities / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D044085:Microfluidics / Q000379:methods*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009005:Monosaccharides / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014527:Uric Acid
chemical_list: C422363:3-glucopyranosyloxybutanolide; D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D009005:Monosaccharides; D016328:NF-kappa B; D014527:Uric Acid; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015107:4-Butyrolactone