The ROS/GRK2/HIF-1α/NLRP3 Pathway Mediates Pyroptosis of Fibroblast-Like Synoviocytes and the Regulation of Monomer Derivatives of Paeoniflorin

Figure 6

Monomeric derivative of paeoniflorin (MDP) inhibits the expression of hypoxia-inducible factor (HIF)-1α through targeted inhibition of GRK2 S670 phosphorylation. (a) Molecular docking modeling of the compound MDP and G protein-coupled receptor kinase 2 (GRK2), the small molecule, and the critical interaction of 3KRW (human GRK2 in complex with Gbetgamma subunits and balanol) are represented by sticks. (b) A schematic representation of the binding mode of MDP in the GRK2 binding site of 3KRW. (c, d) FLS were treated with or without MDP and exposed to hypoxia for 2 h. Immunoblot analysis and quantification of GRK2, p-GRK2 (S670), and HIF-1α. The values are shown as the of the mean (). compared with the control group and ^# compared with the hypoxia group.

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