title: Natural compound methyl protodioscin protects against intestinal inflammation through modulation of intestinal immune responses.
abstract: Dioscoreaceae, a kind of yam plant, has been recommended for treatment of chronic inflammatory conditions. However, the mechanisms are poorly defined. Methyl protodioscin (MPD) is one of the main bioactive components in Dioscoreaceae. Here, we aim to determine the mechanisms by which MPD ameliorates intestinal inflammation. Surgical intestinal specimens were collected from inflammatory bowel diseases (IBD) patients to perform organ culture. Experimental colitis was induced in mice by dextran sulfate sodium (DSS) or Citrobacter rodentium, and was then treated with MPD. NF-κB activation, expression of mucosal pro-inflammatory cytokines, disease severity, and epithelial proliferation/apoptosis were determined. Mouse crypts and Caco-2 monolayers were cultured to observe the effect of MPD upon intestinal epithelial differentiation and barrier function. We found that MPD increased the percentage of survival from high-dose DSS-(4%) treated mice, and accelerated mucosal healing and epithelial proliferation in low-dose DSS-(2.5%) treated mice characterized by marked reduction in NF-κB activation, pro-inflammatory cytokines expression and bacterial translocation. Consistently, MPD protected colonic mucosa from C. rodentium-induced colonic inflammation and bacterial colonization. In vitro studies showed that MPD significantly increased crypt formation and restored intestinal barrier dysfunction induced by pro-inflammatory cytokines. In conclusion, MPD ameliorates the intestinal mucosal inflammation by modulating the intestinal immunity to enhance intestinal barrier differentiation. MPD could be an alternative for treating chronic intestinal inflammatory diseases.
authors.affiliation: The Institute of Molecular Medicine, Peking University Beijing, China.
authors.forename: Rongli
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Shila
authors.initials: S
authors.lastname: Gilbert
authors.affiliation: Jinan University Guangzhou, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Vallance
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Steinbrecher
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, University of Veterinary Medicine Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Madhu
authors.initials: M
authors.lastname: Eluri
authors.affiliation: Xiamen University China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Institute of Molecular Medicine, Peking University Beijing, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Shroyer
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Denson
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) Cincinnati, Ohio, USA.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Han
keywords: Colitis; inflammatory bowel diseases (IBD); intestinal barrier function; intestinal stem cells; methyl protodioscin (MPD); traditional chinese herbal (TCH)