RT Journal Article SR Electronic T1 Caffeic Acid Phenethyl Ester, an Inhibitor of Nuclear Factor-κB, Attenuates Bacterial Peptidoglycan Polysaccharide-Induced Colitis in Rats JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 915 OP 920 VO 299 IS 3 A1 Fitzpatrick, Leo R. A1 Wang, Jian A1 Le, Truc YR 2001 UL http://jpet.aspetjournals.org/content/299/3/915.abstract AB Caffeic acid phenethyl ester (CAPE) is an anti-inflammatory component of propolis (honeybee resin). CAPE is reportedly a specific inhibitor of nuclear factor-κB (NF-κB). The aims of our study were 1) to evaluate the effect of CAPE on cytokine production, NF-κB, and apoptosis in two cell lines; 2) to assess the effect of CAPE on NF-κB in rats with peptidoglycan-polysaccharide (PG-PS)-induced colitis; and 3) to evaluate the efficacy of CAPE against this colitis. In vitro experiments used rat macrophage (NR8383) and colonic epithelial cell (SW620) lines. NF-κB was evaluated by electrophoretic mobility shift assay. Cytokines and apoptosis were measured by enzyme-linked immunosorbent assay. Colitis was induced by intramural injections of PG-PS into the distal colon. CAPE (30 mg/kg) or vehicle was administered once daily to rats by intraperitoneal injection, for 1 week. Various macroscopic and biochemical indices were measured on day 21. CAPE (30 μg/ml) significantly inhibited NF-κB and TNF-α production in the macrophage cell line. In macrophages, CAPE significantly increased DNA fragmentation. CAPE exhibited generally similar effects in the colonic epithelial cell line. CAPE treatment reduced the mean level of colonic NF-κB in rats. CAPE also induced a significant reduction in gross colonic injury. Moreover, colonic cytokine levels (TNF-α and IL-1β) were significantly reduced in CAPE-treated rats. In summary, CAPE inhibits NF-κB, causes a reduction of pro-inflammatory cytokine production, and induces apoptosis in macrophages. These mechanisms likely contributed to the attenuation of PG-PS-induced colitis by CAPE. The American Society for Pharmacology and Experimental Therapeutics