The Immunomodulatory Properties of Propyl-Propane Thiosulfonate Contribute to its Intestinal Anti-Inflammatory Effect in Experimental Colitis

Mol Nutr Food Res. 2019 Mar;63(5):e1800653. doi: 10.1002/mnfr.201800653. Epub 2019 Jan 9.

Abstract

Scope: Propyl-propane thiosulfonate (PTSO) is a component isolated from garlic (Allium sativum) with antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial properties. In consequence, PTSO can be a potential candidate for the treatment of inflammatory bowel diseases.

Methods and results: The anti-inflammatory effects of PTSO are studied in two mice models of colitis: 2,4-dinitrobenzene sulfonic acid (DNBS) (PTSO doses: 0.01-10 mg kg-1 ) and dextran sodium sulfate (DSS) (PTSO doses: 0.01-0.1 mg kg-1 ). The immunomodulatory effects of PTSO (0.1-25 µm) are also shown in vitro in Caco-2 and THP-1 cells, reducing the production of pro-inflammatory mediators and downregulating mitogen-activated protein kinases (MAPKs) signaling pathways. This compound displays beneficial effects in both models of mouse colitis by reducing the expression of different pro-inflammatory mediators and improving the intestinal epithelial barrier integrity. Moreover, PTSO ameliorates the altered gut microbiota composition observed in DSS colitic mice.

Conclusion: PTSO exerts intestinal anti-inflammatory activity in experimental colitis in mice. This anti-inflammatory activity can be associated with the immunomodulatory properties of PTSO through the regulation of the activity of cells involved in the inflammatory response. Furthermore, PTSO is able to restore the intestinal epithelial barrier function and to ameliorate the intestinal microbiota homeostasis, thus supporting its future development in human IBD.

Keywords: Caco-2 cells; DNBS colitis; DSS colitis; PTSO; THP-1 cells; inflammatory bowel disease; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonates / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Caco-2 Cells
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology
  • Dextran Sulfate
  • Dinitrofluorobenzene / analogs & derivatives
  • Disease Models, Animal
  • Garlic / chemistry
  • Gastrointestinal Microbiome / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunologic Factors / pharmacology*
  • Male
  • Mice, Inbred Strains
  • Thiosulfonic Acids / pharmacology*

Substances

  • Alkanesulfonates
  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunologic Factors
  • Thiosulfonic Acids
  • 2,4-dinitrofluorobenzene sulfonic acid
  • Dextran Sulfate
  • Dinitrofluorobenzene