The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist
AbstractPreviously, the authors found that 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) (a phthalimide analogue) bound to and activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Since PPAR-γ suppresses inflammatory responses, the present study was undertaken to investigate the anti-inflammatory effects of PD1. In lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, PD1 suppressed the inductions of pro-inflammatory factors, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Concomitantly, PD1 enhanced the expressions of anti-inflammatory factors, such as arginase-1 and interleukin-10 (IL-10), and suppressed LPS-evoked nuclear factor kappa B (NF-κB) p65 subunit phosphorylation in macrophages. In addition, PPAR-γ activated by PD1 was intensively translocated to the nucleus. These observations suggest that the anti-inflammatory mechanism of PD1 involves inhibition of the NF-κB pathway. In a subsequent in vivo animal experiment conducted using a carrageenan-induced acute inflammatory rat paw edema model, intraperitoneal injection of PD1 significantly reduced paw swelling. Histological analysis of rat paw tissue sections revealed less infiltration of immune cells in PD1-pretreated animals. These findings suggest that PD1 be viewed as a lead compound for the development of novel anti-inflammatory therapeutics. View Full-Text
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Su, M.; Cao, J.; Huang, J.; Liu, S.; Im, D.S.; Yoo, J.-W.; Jung, J.H. The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist. Mar. Drugs 2017, 15, 7.
Su M, Cao J, Huang J, Liu S, Im DS, Yoo J-W, Jung JH. The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist. Marine Drugs. 2017; 15(1):7.Chicago/Turabian Style
Su, Mingzhi; Cao, Jiafu; Huang, Jin; Liu, Sen; Im, Dong S.; Yoo, Jin-Wook; Jung, Jee H. 2017. "The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist." Mar. Drugs 15, no. 1: 7.
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