Lupin Protein Concentrate as a Novel Functional Food Additive That Can Reduce Colitis-Induced Inflammation and Oxidative Stress

Abstract

Food fortification with bioactive compounds may constitute a way to ameliorate inflammatory bowel diseases (IBDs). Lupin seeds contain an oligomer named deflamin that can reduce IBD’s symptoms via MMP-9 inhibition. Here, our goal was to develop a lupin protein concentrate (LPC) enriched in deflamin and to test its application as a food additive to be used as a functional food against colitis. The nutritional profile of the LPC was evaluated, and its efficacy in vivo was tested, either alone or as added to wheat cookies. The LPC presented high protein and carbohydrate contents (20.09 g/100 g and 62.05/100 g, respectively), as well as antioxidant activity (FRAP: 351.19 mg AAE/10 mg and DPPH: 273.9 mg AAE/10 mg). It was also effective against TNBS-induced colitis in a dose dependent-manner, reducing DAI scores by more than 50% and concomitantly inhibiting MMP-9 activity. When added to cookies, the LPC activities were maintained after baking, and a 4-day diet with LPC cookies induced a significant protective effect against acetic acid-induced colitis, overall bringing lesions, oxidative stress and DNA damage levels to values significantly similar to controls (p < 0.001). The results show that the LPC is an efficient way to deliver deflamin in IBD-targeted diets.

Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity

“…Considering previous research on the use of deflamin to inhibit MMP-9 in other animal models of disease [30][31][32][33], we investigated for the first time the biological effect of deflamin in a murine COPD model as a novel approach to explore its therapeutic potential in this disease. Our results demonstrate its efficacy with respect to this objective.…”

“…The authors concluded that deflamin is composed of a complex mixture of different polypeptides derived from the large subunit of δ-conglutin (or heavy chain), as well as a few small fragments of β-conglutin. The bioactive effect of deflamin has been investigated using in vitro models of colon adenocarcinoma [30,31] and in vivo models of ulcerative colitis [32] and tumorigenesis [33]. Among the main biological benefits derived from MMP-9 inhibition in these studies were a decrease in tissue damage and a limitation of markers of cancer progression, such as metastatic capacity and angiogenesis.…”

How to place the duality of specific MMP-9 inhibition for treatment of inflammatory bowel diseases into clinical opportunities?

“…Since 2016 ( 1 ), a limited number of new molecules have been tested in animal model studies of IBD ( Table 2 ). These include betulinic acid ( 57 ), goat whey ( 58 ), polyphenols ( 59 ), eriocitrin ( 60 ), proglitazone ( 61 ), dietary products from grape seeds ( 62 , 67 ) and lupin extracts ( 63 ) and traditional Chinese herbal preparations ( 64 ). In clinical studies, a cannabinoid receptor 2 agonist was found to improve mucosal healing ( 65 ).…”

Therapeutic Potential of Deflamin against Colorectal Cancer Development and Progression

“…So far, deflamin was only successfully tested as a nutraceutical in inflammatory bowel disease models. In mice models of colitis, it significantly inhibited colonic MMP-9 activities, whilst reducing inflammation and colitis-induced lesions, when administered orally as a lupin seed extract or as a food additive to wheat cookies [ 21 , 24 ]. These works showed that deflamin is not only an efficient MMP-9 and MMP-2 inhibitor, but it also is highly resistant to digestion and not absorbed by the digestive tract (our unpublished results).…”

“…These works showed that deflamin is not only an efficient MMP-9 and MMP-2 inhibitor, but it also is highly resistant to digestion and not absorbed by the digestive tract (our unpublished results). These features infer that deflamin holds the potential to act locally in the intestinal path, bypassing the problem of systemic toxicity associated with common MMPIs [ 20 , 21 , 22 , 23 , 24 ]. Moreover, since it is water-soluble and rather effortlessly isolated [ 20 ], deflamin can easily become a novel nutraceutical for pathologies related to aberrant MMP-9 activities, particularly in the digestive system, such as CRC [ 22 ].…”