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Project 3: Moringa Isothiocyanates for Metabolic Resilience Return to Projects

Plant-produced ITCs associated with “superfoods” in the crucifer family are among some of the most biologically active compounds isolated from plants. However, ITCs formed in crucifers, such as broccoli, share inherent thermolability and chemical instability that greatly complicate their use in human medicine. Interestingly, moringa ITCs (MICs) contain an additional sugar residue, conferring much greater stability and appear as solids at room temperature. Moringa is a fast growing tropical tree belonging to the Moringaceae family within the order Brassicales, to which broccoli and other cruciferous vegetables belong. Moringa leaves are historically used as a nutritious and therapeutic food ingredient around the world, particularly for boosting immunity, and maintaining normal blood sugar and blood pressure levels. Stable ITCs such as those from moringa are extremely rare in nature and virtually unexplored as alternatives to beneficial crucifer ITCs. We have developed a simple, single-step extraction/biotransformation method which effectively converts moringa glucosinolates into MICs resulting in a moringa concentrate (MC) containing 3% MICs. None of the currently available moringa supplement products on the market contain significant amounts of MICs, because of the leaf drying methods used. We have shown that MICs can significantly decrease inflammatory cytokine expression in macrophages and reduce glucose production in liver cells more effectively than sulforaphane from broccoli. Using a very high fat diet-induced C57BL/6J mouse hyperglycemia/obesity model, we observed that MC supplementation decreased animal weight gain by 20%, improved blood glucose metabolism, reduced the appearance of fatty liver, and decreased circulating levels of insulin, leptin, TNFα, IL-1β, cholesterol, and triglycerides, compared to the controls. Thus, moringa bioactives have great potential in promoting resistance to metabolic dysfunction from exposure to obesogenic environment.

                

Specific Aims

  • Define, optimize, and standardize bioactives in an aqueous MIC-rich moringa concentrate.  We will evaluate the effect of genetics, environment and physiological factors on ITC content and MC processing techniques as well as standardize MC, define its biochemical fingerprint and botanical authentication/ standardization criteria, and quantify putative bioactives.

 

  • Test specific hypotheses about the molecular and physiological mechanisms involved in systemic MC and MICs action on metabolism and inflammation.  We will identify the effects of MC on inflammatory and metabolic resilience and gene expression in blood, liver, muscle, intestine and adipose tissues from C57BL/6J mice studies and perform functional complex mixture analysis to further validate MICs as main bioactives in MC responsible for changes in energy metabolism and metabolic resilience.  

 

  • Investigate MC and MICs bioavailability and effects on gut microbiome and low-grade intestinal inflammation using transcriptomics approaches.  We will evaluate the bioaccessibility of MICs in the TIM intestinal model and their bioavailability in C57BL/6J mice, test the prediction that MC causes beneficial changes in microbiome ecology and profile the transcriptome of ileum and colon tissues collected from MC-supplemented C57BL/6J mice (with a particular focus on the inflammation-related genes).
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