PMID- 36809720 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20230404 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 117 DP - 2023 Apr TI - Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer. PG - 109839 LID - S1567-5769(23)00162-5 [pii] LID - 10.1016/j.intimp.2023.109839 [doi] AB - It has been reported that colitis is one of risk factors in colorectal cancer (CRC). Intervention of intestinal inflammation and in the early stage of tumorigenesis is of great significance to control the incidence and mortality of CRC. In recent years, natural active products of traditional Chinese medicine have been confirmed that they had made great progress in disease prevention. Here, we showed that Dioscin, a natural active product of Dioscorea nipponica Makino, inhibited initiation and tumorigenesis of AOM/DSS-induced colitis-associated colon cancer (CAC), including alleviating colonic inflammation, improving intestinal barrier function and decreasing tumor burden. In addition, we also explored the immunoregulatory effect of Dioscin on mice. The results showed that Dioscin modulated M1/M2 macrophages phenotype in spleen and decreased monocytic myeloid-derived suppressor cells (M-MDSCs) population in blood and spleen of mice. The in vitro assay demonstrated that Dioscin promoted M1 as well as inhibited M2 macrophages phenotype in LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model. Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Xun, Jing AU - Xun J AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. FAU - Zhou, Siying AU - Zhou S AD - Graduate School, Tianjin Medical University, Tianjin 300100, China. FAU - Lv, Zongjing AU - Lv Z AD - Graduate School, Tianjin Medical University, Tianjin 300100, China. FAU - Wang, Botao AU - Wang B AD - Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China. FAU - Luo, Hai AU - Luo H AD - Graduate School, Tianjin Medical University, Tianjin 300100, China. FAU - Zhang, Lanqiu AU - Zhang L AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. FAU - Yang, Lei AU - Yang L AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. FAU - Zhang, Aimin AU - Zhang A AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China. FAU - Wu, Xueliang AU - Wu X AD - Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China. FAU - Wang, Zhenyu AU - Wang Z AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. FAU - Wang, Ximo AU - Wang X AD - Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin Medical University, Tianjin 300100, China. FAU - Yu, Xiangyang AU - Yu X AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. Electronic address: yxynankai@126.com. FAU - Zhang, Qi AU - Zhang Q AD - Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. Electronic address: zhangqi8501@126.com. LA - eng PT - Journal Article DEP - 20230219 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 3B95U4OLWV (dioscin) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Mice MH - Animals MH - *Colitis-Associated Neoplasms/drug therapy MH - *Myeloid-Derived Suppressor Cells/pathology MH - Carcinogenesis MH - *Colitis/chemically induced/complications/drug therapy MH - Inflammation/pathology MH - Macrophages MH - Cell Differentiation MH - Dextran Sulfate/pharmacology MH - Mice, Inbred C57BL MH - Disease Models, Animal OTO - NOTNLM OT - Colitis-associated colorectal cancer OT - Dioscin OT - Macrophage polarization OT - Myeloid-derived suppressor cells OT - Tumorigenesis COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/02/23 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/02/22 14:06 PHST- 2022/12/06 00:00 [received] PHST- 2023/01/17 00:00 [revised] PHST- 2023/01/30 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/02/23 06:00 [pubmed] PHST- 2023/02/22 14:06 [entrez] AID - S1567-5769(23)00162-5 [pii] AID - 10.1016/j.intimp.2023.109839 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Apr;117:109839. doi: 10.1016/j.intimp.2023.109839. Epub 2023 Feb 19.