title: Pharmacology and Clinical Effect of Platonin, a Cyanine Photosensitizing Dye: Potential Molecular Targets.
abstract: Platonin, a photosensitizing dye, is known to possess antioxidant and anti-inflammatory activity. Platonin has been used to treat trauma, ulcers and some acute inflammations and it also reported to improve blood circulation and reduce mortality in endotoxin-induced rat models. Our previous studies established that platonin suppresses the lipopolysaccharides (LPS)-induced inflammatory cytokines, including interleukin-1β (IL-1β-+), IL-6, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS). Nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) transcription factors are reported to be essential in mediating the endotoxin-induced production of inflammatory molecules. In vivo studies from our groups revealed that platonin has potential effects on inhibiting pyrogen release, tissue damage and ischemia during heatstroke, ischemia reperfusion injury in lungs and also improve the survival of skin allografts in rats. Clinically, this compound has been proven to cure juvenile rheumatoid arthritis (JRA) and polyarteritis nodosa (PN). In this review, we summarize the pharmacological and clinical effects of platonin via describing the potential molecular mechanism of regulation of inflammatory molecules of mitogen-activated protein kinases (MAPKs), including extracellular regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK and also NF-kB activation. Moreover, this paper discusses the signaling pathways expedited by NF-kB, AP-1, MAPKs and NO/NOS, these all have been reflected in inflammatory processes, and could be the encouraging molecular targets for the design of pharmaceutical drugs targeting antiinflammatory therapy.
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Chia-Fu
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences, Department of Pharmacology, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan. sheujr@tmu.edu.tw.
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.forename: Thanasekaran
authors.initials: T
authors.lastname: Jayakumar
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D013844:Thiazoles; C032149:platonin; D052247:Nitric Oxide Synthase Type II