platonin and Inflammation

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.

Topics: Animals; Cell Cycle; Humans; Inflammation; NF-kappa B; Nitric Oxide Synthase Type II; Rats; Signal Transduction; Thiazoles

The aim of this study was to investigate the therapeutic effect of platonin, a cyanine photosensitizing dye as well as an inhibitor of proinflammatory cytokines, in an animal model of heat stroke. Anesthetized rats, immediately after the onset of heat stroke, were divided into two major groups and given the following: normal saline (1 mL per kg body weight) intravenously, or platonin (12.5-50 microg/mL per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heat stroke. Another group of rats was exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 18 to 22 min. Resuscitation with intravenous doses of platonin, but not normal saline, immediately at the onset of heat stroke, significantly improved survival during heat stroke (41-147 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor-alpha, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, and D-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase, and striatal levels of partial pressure of oxygen, local cerebral blood flow, glycerol, glutamate, and lactate/pyruvate were all elevated during heat stroke. The systemic inflammation, hypercoagulable state, and cerebral ischemia and injury during heat stroke were all significantly suppressed by platonin. The data demonstrate that platonin therapy may resuscitate heat stroke victims by reducing circulatory shock, systemic inflammation, hypercoagulable state, and tissue ischemia and injury.

Topics: Animals; Blood Coagulation; Cell Hypoxia; Heat Stroke; Inflammation; Injections, Intravenous; Ischemia; Photosensitizing Agents; Rats; Rats, Sprague-Dawley; Shock; Thiazoles

Platonin is believed to be an immunomodulator, because it has been shown to be effective only in chronic inflammation models in rat adjuvant arthritis. Platonin did not suppress the serotonin-, histamine- and bradykinin-induced paw edemata of mice when injected 0-1 hr before these irritants in the standard methods. When platonin was administered 3 hr before challenge, however, all of these inflammations were significantly suppressed. Platonin required at least 1 hr of lag for onset of inhibition, just as dexamethasone, and was effective only in the range of 10-320 micrograms/kg. Inhibition of serotonin-induced paw edema by platonin was impaired by concomitant injection of cycloheximide and was not affected by adrenalectomy. Platonin was concluded to suppress the vascular permeability principally through enhancing the endogenous anti-inflammatory protein (vasoregulin) synthesis without changing arachidonate metabolism, lymphocyte transformation or antibody production. Rat carrageenan paw edema was also suppressed when this drug was administered 2-4 hr before challenge.

Topics: Acute Disease; Animals; Cycloheximide; Dexamethasone; Inflammation; Male; Mice; Mice, Inbred ICR; Rats; Rats, Inbred Strains; Thiazoles