Ganoderma lucidum polysaccharides reduce methotrexate-induced small intestinal damage in mice via induction of epithelial cell proliferation and migration.
OBJECTIVE
To study the effects of Ganoderma lucidum polysaccharides (Gl-PS) on methotrexate (MTX)-induced small intestinal damage in mice and the underlying mechanisms.


METHODS
BALB/c mice were used for in vivo study. The mice were administered with Gl-PS (50, 100, or 200 mg/kg, ig) for 10 d, and injected with MTX (50 mg/kg, ip) on d 7 and 8 to induce intestinal damage, and then sacrificed on d 11 for morphological study and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) measurements. Before sacrificing, blood samples were collected to analyze immunoglobulin A (IgA). Rat intestinal IEC-6 cells were used for in vitro study. Cell proliferation and migration were assessed using MTT method and an in vitro wounding model, respectively. Transforming growth factor β (TGFβ) protein expression was determined using ELISA assay. Ornithine decarboxylase (ODC) and c-Myc mRNA expression profiles were determined using RT-PCR.


RESULTS
MTX treatment caused severe mucosal damage, significantly increased small intestine MDA levels, and decreased SOD and serum IgA levels in BALB/c mice. Gl-PS (100 and 200 mg/kg) markedly reversed the MTX effects. In IEC-6 cells, Gl-PS (0.1, 1, and 10 μg/mL) significantly stimulated the cell proliferation. Furthermore, Gl-PS (10 μg/mL) significantly stimulated the cell migration. In addition, Gl-PS (10 and 20 μg/mL) significantly increased the expression of ODC and c-Myc mRNAs. However, Gl-PS (up to 20 μg/mL) had no effect on the expression of TGFβ protein.


CONCLUSIONS
The results suggest that Gl-PS protects small intestine against MTX-induced injury via induction of epithelial cell proliferation and migration.
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Li-hua
LH
Chen
Zhi-bin
ZB
Lin
Wei-dong
WD
Li
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D007421:Intestine, Small / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D008727:Methotrexate / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry*
D011134:Polysaccharides; D008727:Methotrexate