Frondanol, a Nutraceutical Extract from Cucumaria frondosa, Attenuates Colonic Inflammation in a DSS-Induced Colitis Model in Mice.

Sandeep Subramanya,Aisha Al Zahmi,Peter Collin,Samira Al Zadjali,Sanjana Chandran,Radeya Al Katheeri,Thomas Adrian,Saeeda Almarzooqi,Vishnu Raj

doi:10.3390/md16050148

Sandeep Subramanya, Aisha Al Zahmi + Show 7 more

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https://doi.org/10.3390/md16050148

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Abstract

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.

Highlights

Inflammatory bowel disease (IBD) refers to Crohn’s disease (CD) or ulcerative colitis (UC), which involve both small and large intestines
Frondanol administration significantly prevented the increase in the disease activity index (DAI) score in dextran sodium sulfate (DSS)-treated animals (p < 0.05, Figure 1)
Frondanol alone had no significant effect on the DAI score compared with the control

Summary

Introduction

Inflammatory bowel disease (IBD) refers to Crohn’s disease (CD) or ulcerative colitis (UC), which involve both small and large intestines. IBD is characterized by chronic inflammation with mucosal ulceration in the intestinal tract [1]. The prevalence of IBD is increasing (150–250/100,000) in developed nations [2], and greatly diminishes quality of life because of the morbidity associated with. Mar. Drugs 2018, 16, 148; doi:10.3390/md16050148 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2018, 16, 148 it such as pain, vomiting, and diarrhea. The current mainstream therapies for IBD are sulfasalazine, corticosteroids, immunosuppressive agents such as azatriopine, and anti-tumor necrosis factor-α antibodies, either as single agents or in combination, to inhibit aberrant immune response and inflammation. With the lack of effective treatment, in addition to the associated side effects and costs, many IBD patients turn to complementary and alternate therapy [4]

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