Abstract

Chronic inflammation is considered a pressing health issue that needs resolving. Inflammatory disease such as inflammatory bowel disease requires a long-term medical regimen to prevent disease progression. Conventionally, lactoferrin is used to treat mild gastrointestinal tract and skin inflammation. Protease-digested lactoferrin fragments often exhibit improved therapeutic properties compared to full-length lactoferrin (flHLF). However, there are no studies on the use of protease-digested lactoferrin fragments to treat inflammation. Herein, we assess the anti-inflammatory properties of engineered recombinant lactoferrin fragments (rtHLF4, rteHLF1, and rpHLF2) on non-malignant colonic fibroblast cells and colorectal cancer cells. We found that rtHLF4 is 10 times more effective to prevent inflammation compared to flHLF. These results were investigated by looking into the reactive oxygen species (ROS) production, angiogenesis activity, and cellular proliferation of the treated cells. We have demonstrated in this study the anti-inflammatory properties of the flHLF and the various lactoferrin fragments. These results complement the anti-cancer properties of these proteins that were demonstrated in an earlier study.

Highlights

  • Patients suffering from inflammatory bowel disease (IBD) are more at risk of developing colorectal cancer in the later stages of their lives (Barral et al, 2016)

  • We identified three lactoferrin fragments exhibiting improved anti-cancer activity. recombinant engineered-lactoferrin 4 (rtHLF4), in particular, showed up to 100-fold improved anti-cancer activity against various cancer cell lines compared to full-length lactoferrin (flHLF) (Pan et al, 2021)

  • We observed that the rtHLF4 and flHLF protein could negate the indomethacininduced hemolytic activity

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Summary

Introduction

Patients suffering from inflammatory bowel disease (IBD) are more at risk of developing colorectal cancer in the later stages of their lives (Barral et al, 2016). Anti-Inflammatory and Anti-Oxidative Lactoferrin Fragments aminosalicylates (Gisbert et al, 2007), corticosteroids (Waljee AK et al, 2016), immunomodulators (Biancone et al, 2014), and probiotic microbial regiment (Scaldaferri et al, 2013), whereas severe cases of IBD require open surgery to resect damaged tissues within the gastrointestinal tract (Maggiori and Panis, 2013). There is an increasing need to develop less invasive treatments with higher efficacy to treat IBD

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