Caffeic acid phenethyl ester (CAPE) is an anti-inflammatory component of
propolis (honeybee resin). CAPE is reportedly a specific inhibitor of
nuclear factor-kappaB (
NF-kappaB). The aims of our study were 1) to evaluate the effect of CAPE on
cytokine production,
NF-kappaB, and apoptosis in two cell lines; 2) to assess the effect of CAPE on
NF-kappaB 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-kappaB 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 microg/ml) significantly inhibited
NF-kappaB and
TNF-alpha 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-kappaB in rats. CAPE also induced a significant reduction in gross colonic injury. Moreover, colonic
cytokine levels (
TNF-alpha and IL-1beta) were significantly reduced in CAPE-treated rats. In summary, CAPE inhibits
NF-kappaB, 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.