RT Journal Article SR Electronic T1 Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-kappa B activation JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.110.170852 DO 10.1124/jpet.110.170852 A1 Pei Luo A1 Yuen Fan Wong A1 Lin Ge A1 Zhi Feng Zhang A1 Yuan Liu A1 Liang Liu A1 Hua Zhou YR 2010 UL http://jpet.aspetjournals.org/content/early/2010/09/21/jpet.110.170852.abstract AB Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anti-carcinogenic, anti-inflammatory and analgesic activities. However, the mechanism underlying its' anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg; we also examined the role of NF-κB and pro-inflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various pro-inflammatory mediators, including histamine, serotonin, bradykinin and prostaglandin E2. PL reduced the number of writhing episodes of mice induced by intraperitoneal injection of acetic acid. But it did not reduce the writhing episode numbers induced by MgSO4 in mice and it did not prolong the tail flick reaction time of rats to noxious thermal pain either. Mechanistic studies showed that PL effectively decreased the production of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. It also inhibited the expression of pro-inflammatory mediators iNOS and COX-2 while did not inhibit the expression of COX-1. Further studies demonstrated that PL suppressed IκBα phosphorylation and degradation and thus inhibited the phosphorylation of p65 subunit of NF-κB. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.