The crude
powder of the fruit of Arctium lappa L. (ALF) has previously been reported to attenuate experimental
colitis in mice. But, its main effective ingredient and underlying mechanisms remain to be identified. In this study, ALF was extracted with
ethanol, and then successively fractionated into
petroleum ether,
ethyl acetate,
n-butanol and water fraction. Experimental
colitis was induced by
dextran sulfate sodium (DSS) in mice. Among the four fractions of ALF, the
ethyl acetate fraction showed the most significant inhibition of DSS-induced
colitis in mice. The comparative studies of
arctigenin and
arctiin (the two main ingredients of
ethyl acetate fraction) indicated that
arctigenin rather than
arctiin could reduce the loss of
body weight, disease activity index and histological damage in the colon.
Arctigenin markedly recovered the loss of intestinal epithelial cells (
E-cadherin-positive cells) and decreased the infiltration of neutrophils (MPO-positive cells) and macrophages (CD68-positive cells).
Arctigenin could down-regulate the expressions of TNF-α,
IL-6, MIP-2, MCP-1, MAdCAM-1,
ICAM-1 and
VCAM-1 at both
protein and
mRNA levels in colonic tissues. Also, it markedly decreased the MDA level, but increased SOD activity and the GSH level. Of note, the efficacy of
arctigenin was comparable or even superior to that of the positive control
mesalazine. Moreover, it significantly suppressed the phosphorylation of MAPKs and the activation of NF-κB, including phosphorylation of IκBα and p65, p65 translocation and
DNA binding activity. In conclusion,
arctigenin but not
arctiin is the main active ingredient of ALF for attenuating
colitis via down-regulating the activation of MAPK and NF-κB pathways.