Lunasin protease inhibitor concentrate decreases pro-inflammatory cytokines and improves histopathological markers in dextran sodium sulfate-induced ulcerative colitis

Authors: NIETO-VELOZA, ANDREA - University Of Tennessee; WANG, ZHIHONG - University Of Tennessee; ZHONG, QIXIN - University Of Tennessee; D'SOUZAA, DORIS - University Of Tennessee; Krishnan, Hari; DIA, VERMONT - University Of Tennessee

Submitted to: Food Science and Human Wellness
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2020
Publication Date: 7/18/2022
Citation: Nieto-Veloza, A., Wang, Z., Zhong, Q., D'Souzaa, D., Krishnan, H.B., Dia, V.P. 2022. Lunasin protease inhibitor concentrate decreases pro-inflammatory cytokines and improves histopathological markers in dextran sodium sulfate-induced ulcerative colitis. Food Science and Human Wellness. 11(6):1508-1514. https://doi.org/10.1016/j.fshw.2022.06.008.
DOI: https://doi.org/10.1016/j.fshw.2022.06.008

Interpretive Summary: Plant-derived bioactive peptides are of major interest due to their ability to modulate biological and physiological functions, thus providing health benefits for the consumers. Soybean-derived peptides have demonstrated properties against different pathological conditions such as hypertension, diabetes, inflammation, and cancer. Lunasin protease inhibitor concentrate (LPIC) may exert anti-inflammatory activity with potential application against inflammation mediated diseases. Ulcerative colitis (UC) is a condition of chronic inflammation in the large intestine that has potential to increase the risk of developing colorectal cancer. In this study, we examined the anti-inflammatory activity of LPIC against ulcerative colitis. Our results suggest that combinations of peptides in LPIC may significantly reduce the histopathological damage, hence LPIC may be utilized as a possible therapeutic strategy to treat ulcerative colitis. Information from this study will enable scientists to exploit soybean lunasin protease inhibitor concentrate for the management of disorders such as inflammatory bowel disease.

Technical Abstract: Lunasin Protease Inhibitor Concentrate (LPIC) is a novel combination of soy bio-active peptide lunasin, Kunitz and Bowman-Birk protease inhibitors. The reported anti-inflammatory and anticancer properties of each one of them suggest LPIC as a promising candidate for the treatment of inflammatory-related diseases. Our objective was to assess the in vivo anti-inflammatory properties of LPIC. First, an in vitro test was performed in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages by measuring the production of nitric oxide (NO), IL-6, and TNF-a as inflammatory markers. For the in vivo model, ulcerative colitis was induced in mice via oral administration of dextran sodium sulfate (DSS). LPIC treatment was performed via daily intra-peritoneal injection of 50 mg/kg body weight. Body weight, visible blood in stool and stool consistency were scored daily as macroscopic indicators of disease progression. Occult blood was evaluated by the presence of hemoglobin in stool every third day. Colon length, caecum weight, colonic myeloperoxidase activity (MPO), presence of pro-inflammatory cytokines in blood and colon, changes in the architecture, and expression of inducible nitric oxide synthase (iNOS) in colonic tissue were evaluated. In vitro, LPIC induced production of NO and maintained cytokine levels in comparison to activated untreated macrophages. In vivo, LPIC increased colonic bleeding and did not improve macroscopic markers of the disease, but reduced colonic IL-1ß and IL-6, decreased systemic circulation of TNF-a, attenuated neutrophils infiltration and iNOS expression in colonic tissue, and diminished the damage in colonic architecture. Our results suggest that combinations of peptides in LPIC may counteract the anti-inflammatory properties in vitro; while in vivo, LPIC can significantly reduce the histopathological damage, hence is a possible therapeutic strategy to attenuate UC.