OBJECTIVE:To test the hypothesis that modified Shenlingbaizhu decoction (MSD) attenuates the formation of intestinal adenomas by regulating activation of CD4+CD25+ forkhead box P3 (FoxP3) regulatory T cells (Tregs) by downregulation of hypoxia-inducible factor 1 α (HIF-1 α).METHODS:Chemical fingerprints of ginsenoside Rb1,ginsenoside Rc,paeoniflorin,and dioscin in standard extractions were used as material bases of MSD.Adenomatous polyposis coli multiple intestinal neoplasia (ApcMin/+) mice,which harbor a mutation in adenomatous polyposis coli,were used to host intestinal adenomas.Peripheral blood and spleen Tregs were analyzed by flow cytometry.Protein expression was analyzed by immunohistochemistry and West blotting.RESULTS:The number and size of intestinal adenomas were significantly reduced by MSD treatment.Mucosal thickening and the spleen size were also substantially decreased by MSD.The carcinogenesis process in ApcMin/+ mice resembled that of human colorectal cancer.Molecular markers of neoplasms,such as β-catenin,cyclooxygenase-2,proliferating cell nuclear antigen,and p53,were substantially ameliorated by MSD treatment.Moreover,MSD downregulated peripheral and spleen CD4+ CD25+FoxP3+ Tregs and reduced in situ expression of CD4,CD25,and FoxP3 in intestinal adenomas.MSD also suppressed HIF-1α expression in the intestinal adenomas,and HIF-1α inhibition decreased expression of FoxP3 in Jurkat T cells under hypoxic conditions.CONCLUSION:MSD is a valid prescription to control the formation of intestinal adenomas in ApcMin+/+ mice.It exerts anti-cancer effects partially through suppression of HIF-1α that induced activation of CD4+CD25+FoxP3+ Tregs in vivo and in vitro.