P025 Matrine induces intestinal apoptosis in dextran sulfate sodium-induced colitis
J.S. Koo*, B. Keum, B.J. Lee, Y.J. Jeen
Korea University College of Medicine, Department of Internal Medicine, Seoul, Korea, Republic of
Matrine, the major alkaloid component from Sophora flavescens, has been used to treat chronic hepatitis in China. It has been reported that matrine has several pharmacological effects including regulation of immune reaction. However, the impact of matrine is unknown on intestinal apoptosis.
Intestinal epithelial cells (IEC-18) were used to determine the in vitro effect of matrine on LPS-induced apoptosis signaling. The therapeutic efficacy of matrine was assessed using dextran sulfate sodium (DSS) induced colitis model with mice. Matrine (100 or 200 mg/kg) was administered by using oral gavage. Disease activity index including weight loss, stool consistency, and stool blood and histology score was used to determine the colitis severity. Apoptosis of mouse was evaluated with Western blot and TUNEL assay.
In vitro study, the expression of Bax significantly increased, Bcl-2 and Cox decreased in IEC-18 cells treated with matrine. The effect for inhibition of appoptosis, evaluated by Western blot was increased with dose of matrine. In DSS-induced acute colitis, disease activity index and histological scores were not significantly different among the mice groups according to the matrine treatment. As shown in vitro study, the expression of Bcl-2 was decreased in the matrine treatment mice. However, Bax was increased in low dose matrine (100 mg/kg) and decreased in high dose (200 mg/kg). In the same manner, cleaved Caspase-3 was increased in the mice group treated with low dose matrine. Furthermore, Tunel assay in colon tissues of matrine treated mice was not significantly different with that of matrine untreated mice.
Although matrine didn't have significant effect on inhibiting intestinal inflammation, matrine increased the apoptosis on LPS-induced IEC-18 cells and DSS-induced colitis through decrease of Bcl-2 and increase of Bax and cleaved Caspase-3.