Norisoboldine (NOR), the main active constituent of Radix Linderae, was previously demonstrated to ameliorate
collagen-induced arthritis in rats through regulating the imbalance of T cells in intestines, which implied its therapeutic potential in
inflammatory bowel disease. Here, we investigated the effect of NOR on
ulcerative colitis (UC) induced by
dextran sulfate sodium (DSS) in mice. Results showed that NOR (20, 40mg/kg) markedly reduced the symptoms of
colitis, the levels of IL-1β and TNF-α, and the activation of ERK,
p38 MAPK and NF-κB-p65. NOR only slightly decreased the levels of IFN-γ and
IL-17A in mouse colons, but it dramatically increased the level of
IL-10 at both
protein and
mRNA grades. Consistently, NOR increased the number of CD4(+)CD25(+)Foxp3(+) Treg cells more obviously than it decreased that of CD4(+)IL-17(+) Th17 cells in mesenteric lymph nodes (MLNs) and colonic lamina proprias (LPs) of
colitis mice, and promoted the expression of Foxp3
mRNA in colon tissues. It could facilitate the in vitro differentiation of Treg cells from naive T cells and promote the phosphorylations of Smad2/3 in colon tissues of
colitis mice. On the other hand, NOR did not affect the expressions of homing receptors CCR9 and α4β7 in SPs, and homing
ligands CCL25 and Madcam-1 in MLNs and colonic LPs, suggesting that the increase of Treg cells in colons by NOR was not due to gut homing. In conclusion, NOR can ameliorate DSS-induced UC in mice, and the mechanisms involve reduction of pro-inflammatory
cytokines and selective induction of Treg cells in colons.