ABSTRACT
Plant-based compounds or phytochemicals such as alkaloids, glycosides, flavonoids, volatile oils, tannins, resins, and polyphenols have been used extensively in traditional medicine for centuries and more recently in Western alternative medicine. Extensive evidence suggests that consumption of dietary polyphenolic compounds lowers the risk of inflammatory diseases. The anti-inflammatory properties of several phytochemicals are mediated through ligand-inducible peroxisome proliferator-activated receptors (PPARs), particularly the PPARγ transcription factor. Inflammatory bowel disease (IBD) is represented by ulcerative colitis, which occurs in the mucosa of the colon and rectum, and Crohn's disease (CD) that can involve any segment of gastrointestinal tract. Because of the lack of cost-effective pharmaceutical treatment options, many IBD patients seek and use alternative and unconventional therapies to alleviate their symptoms. PPARγ plays a role in the inhibition of inflammatory cytokine expression and activation of anti-inflammatory immune cells. The phytochemicals reported here are ligands that activate PPARγ, which in turn modulates inflammatory responses. PPARγ is highly expressed in the gut making it a potential therapeutic target for IBDs. This review summarizes the effects of the currently published phytochemicals that modulate the PPARγ pathway and reduce or eliminate colonic inflammation.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , PPAR gamma/metabolism , Anti-Inflammatory Agents/pharmacology , Humans , Inflammatory Bowel Diseases/pathologyABSTRACT
Frondanol is a nutraceutical lipid extract of the intestine of the edible Atlantic sea cucumber, Cucumaria frondosa, with potent anti-inflammatory effects. In the current study, we investigated Frondanol as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were given 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. The colitis group received oral Frondanol (100 mg/kg body weight/per day by gavage) and were compared with a control group and the DSS group. Disease activity index (DAI) and colon histology were scored for macroscopic and microscopic changes. Colonic tissue length, myeloperoxidase (MPO) concentration, neutrophil and macrophage marker mRNA, pro-inflammatory cytokine proteins, and their respective mRNAs were measured using ELISA and real-time RT-PCR. The tissue content of leukotriene B4 (LTB4) was also measured using ELISA. Frondanol significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue MPO concentrations, neutrophil and macrophage mRNA expression (F4/80 and MIP-2), and pro-inflammatory cytokine content (IL-1β, IL-6 and TNF-α) both at the protein and mRNA level were significantly reduced by Frondanol. The increase in content of the pro-inflammatory mediator leukotriene B4 (LTB4) induced by DSS was also significantly inhibited by Frondanol. It was thus found that Frondanol supplementation attenuates colon inflammation through its potent anti-inflammatory activity.