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.

Frontline Science: Reprogramming COX-2, 5-LOX, and CYP4A-mediated arachidonic acid metabolism in macrophages by salidroside alleviates gouty arthritis

“…Gout is triggered by monosodium urate (MSU) crystal deposition in and around joints. Macrophages play a pivotal role in the initiating, progression, and resolution of gouty arthritis . Under different stimuli, macrophages can polarize into different phenotypes: the two extremes of the phenotypic spectrum of macrophages are defined as the classically activated M1‐like phenotype and the alternatively activated M2‐like phenotype .…”

Evaluation of changes in the growth and chemical constituents of Anoectochilus formosanus Hayata grown under hydroponic conditions

“…A number of biological compounds which showed strong antioxidant activity, eg. glycosides, H.C. Nguyen,T.Q.M.Nhu,P.V.Dung et al 376 have been found in A. formosanus (Du et al, 2000;Wang et al, 2002;Han et al, 2016). Du and coworkers (2000) have isolated megastigma glycosides and butanoic acid glucoside, whereas Wang and coworkers (2002) and Du and coworkers (1998) have identified a kinsenoside and kinsenone, respectively.…”

“…This is an ornamental plant often called "King medicine", because of its high pharmacological potential. Its extract possess hepatoprotective (Fang et al, 2008;Cheng and Chang, 2009), anti-diabetic (Rehman et al, 2015), anti-inflammatory (Hsiao et al, 2016), antitumor (Tseng et al, 2006;Yang et al, 2014;Yang et al, 2017), anti-arthritic (Han et al, 2016), and immunomodulatory activities (Yang et al, 2014;Yang et al, 2017). These pharmaceutical properties are due to the activities of many phytochemicals, including alkaloids, flavonoids, terpenoids, steroids, and their derivatives, which are present in various parts of this plant (Ng et al, 2011;Zhang et al, 2013).…”

<p>Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway</p>

“…10 Meanwhile, the inflammatory response is activated as well. 11,12 In this paper, we mainly explored the regulatory effect of metformin on the proliferative and apoptotic changes in TPC-1 cells and the involvement of LRP2 and the JNK pathway.…”