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Research Article | Open Access

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

Andrea Nieto-Velozaa, Zhihong Wanga, Qixin Zhonga, Doris D’Souzaa, Hari B. Krishnanb, Vermont P. Diaa( )
Department of Food Science, University of Tennessee, Knoxville 37996, USA
Agricultural Research Service, USDA, Columbia 65211, USA

Peer review under responsibility of KeAi Communications Co., Ltd.

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Abstract

Lunasin protease inhibitor concentrate (LPIC) is a novel combination of soy bioactive 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 RAW264.7 murine macrophages by measuring the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) as inflammatory markers. For the in vivo model, ulcerative colitis (UC) was induced in mice via oral administration of dextran sodium sulfate (DSS). LPIC treatment was performed via daily intraperitoneal 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-1β and IL-6, decreased systemic circulation of TNF-α, 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.

Keywords

InflammationCytokinesUlcerative colitisBio-peptidesProtease inhibitor

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Food Science and Human Wellness
Volume 11 Issue 6,
November 2022
Pages 1508-1514
DOI: 10.1016/j.fshw.2022.06.008
Cite this article:
Nieto-Veloza A, Wang Z, Zhong Q, et al. Lunasin protease inhibitor concentrate decreases pro-inflammatory cytokines and improves histopathological markers in dextran sodium sulfate-induced ulcerative colitis. Food Science and Human Wellness, 2022, 11(6): 1508-1514. https://doi.org/10.1016/j.fshw.2022.06.008

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Received: 15 June 2020
Revised: 01 November 2020
Accepted: 04 November 2020
Published: 18 July 2022
© 2022 Beijing Academy of Food Sciences.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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