title: Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through suppressing G-protein-coupled receptor kinase 2.
abstract: Paeoniflorin (Pae) is a monoterpene glucoside and the main component of the total glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora. Its anti-inflammatory effect is associated with regulating G-protein-coupled receptors (GPCRs) signaling. The aim of this study was to explore the expression change of G-protein-coupled receptor kinase 2 (GRK2) in fibroblast-like synoviocytes (FLS) and the effect of Pae. Pae was obtained and purified from the roots of Paeonia lactiflora. We investigated the expression of GRK2 in synovium during the inflammatory process and assessed the effects of a specific GRK2 inhibitor and Pae on proliferation, cAMP level, and protein kinase A (PKA) activity of FLS in vitro. Additionally, the effect of Pae on GRK2 expression in FLS was detected in vitro. Expression of GRK2 in synovium from CIA rats increased during the inflammatory process. The specific GRK2 inhibitor suppressed proliferation and increased the cAMP level as well as PKA activity of FLS, and Pae had the same effects. Furthermore, Pae decreased GRK2 expression in FLS in vitro. Our results indicate that a chronic inflammatory process in CIA induces upregulation of GRK2 expression in FLS, and Pae can reverse this change, which might be one of the important mechanisms for Pae regulating GPCRs signaling and suppressing the proliferation of FLS in CIA.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunodrugs, Education Ministry of China, Hefei, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Hua-Xun
authors.initials: HX
authors.lastname: Wu
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.forename: Qing-Tong
authors.initials: QT
authors.lastname: Wang
authors.forename: Wu-Yi
authors.initials: WY
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D003094:Collagen; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D039821:Monoterpenes; D029596:Paeonia / Q000737:chemistry; D008517:Phytotherapy; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects / Q000201:enzymology*; D006027:Glycosides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001565:Benzoates; D001952:Bridged-Ring Compounds; D003094:Collagen; D004791:Enzyme Inhibitors; D054769:G-Protein-Coupled Receptor Kinase 2; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides