Anti-inflammatory and chemopreventive activity of lunasin from tofu whey for the management of gastrointestinal diseases

Gastrointestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are pathological conditions associated with chronic inflammation, characterized by intestinal damage, debilitating symptoms, and detrimental health consequences. The increased risk of CRC in IBD patients, and the adverse effects associated with current therapeutic strategies, point out the need for safer alternatives to reduce chronic inflammation in the bowel. Lunasin is a bioactive peptide naturally occurring in soybeans, with chemopreventive and anti-inflammatory properties demonstrated in several extra-intestinal diseases. However, to date, there is no evidence of the biological activity of lunasin on the gastrointestinal tract as a target site. The objective of this research was to investigate the biological activity of lunasin against bowel-related diseases using in vivo models. First, lunasin was isolated from tofu wastewater applying a designed process that combines precipitation techniques and chromatographic purification. The three-step isolation process was applied to industrially produced tofu wastewater yielding 773mg lunasin of 80% purity per kg dry tofu whey, with anti-inflammatory properties as tested in vitro using activated murine macrophages. Then, the anti-inflammatory activity of lunasin in the gut was determined using an in vivo model of spontaneous colitis. Oral administration of lunasin reduced pro-inflammatory cytokines throughout the small and large intestines and decreased the frequency of clinical manifestations of IBD in IL-10^-/- mice. In vitro analysis indicated that the mechanism of action is partially associated with the ability of lunasin to modulate the activation of the NLRP3 inflammasome. Finally, the chemopreventive activity of lunasin in the bowel was evaluated using an in vivo model of colitis-associated CRC. Oral administration of lunasin decreased the impact of inflammation over the colon, facilitated recovery from episodes of mild and moderate inflammation, reduced tumor burden, and mitigated the progression of malignant features. The results of this study demonstrate 1) the presence of bioactive lunasin in tofu wastewater, 2) the anti-inflammatory and chemopreventive activity of lunasin in the bowel, and 3) the modulatory activity of lunasin over the NLRP3 inflammasome. This research can serve as a basis for further investigation on the active incorporation of lunasin for the management of IBD.