A Novel Peptide Ameliorates LPS-Induced Intestinal Inflammation and Mucosal Barrier Damage via Its Antioxidant and Antiendotoxin Effects.
Zhang. Lulu L; Wei. Xubiao X; Zhang. Rijun R; Si. Dayong D; Petitte. James N JN; Ahmad. Baseer B; Zhang. Manyi M
Key Findings
- The hybrid peptide LTP has a longer half‑life and lower cytotoxicity than its parent peptides.
- LTP significantly reduces inflammatory cytokines (TNF‑α, IFN‑γ, IL‑6) and improves gut barrier proteins (ZO‑1, occludin) in LPS‑treated mice.
- Its anti‑inflammatory action appears to involve LPS neutralization, oxidative stress reduction, and inhibition of NF‑κB signaling.
Practical Outcomes
- While LTP is not yet available for human use, the study shows that designing hybrid peptides can boost gut‑protective effects and safety. For biohackers, this suggests that future peptide‑based supplements targeting intestinal health may become more effective and tolerable, but more human research is needed before any self‑experimentation.
Summary
Researchers created a new hybrid peptide (called LTP) by joining parts of two natural peptides, LL‑37 and TP5. In mice with gut inflammation caused by bacterial endotoxin (LPS), LTP lasted longer in the body, was less toxic, and reduced weight loss, tissue damage, and inflammatory signals better than the original peptides. It also helped keep the gut lining tighter and lowered oxidative stress.
Abstract
Intestinal inflammation is an inflammatory disease resulting from immune dysregulation in the gut. It can increase the risk of enteric cancer, which is a common malignancy globally. As a new class of anti-inflammatory agents, native peptides have potential for use in the treatment of several intestinal inflammation conditions; however, their potential cytotoxicity and poor anti-inflammatory activity and stability have prevented their development. Hybridization has been proposed to overcome this problem. Thus, in this study, we designed a hybrid peptide (LL-37-TP5, LTP) by combing the active centre of LL-37 (13-36) with TP5. The half-life and cytotoxicity were tested in vitro, and the hybrid peptide showed a longer half-life and lower cytotoxicity than its parental peptides. We also detected the anti-inflammatory effects and mechanisms of LTP on Lipopolysaccharide (LPS)-induced intestinal inflammation in murine model. The results showed that LTP effectively prevented LPS-induced weight loss, impairment of intestinal tissues, leukocyte infiltration, and histological evidence of inflammation. Additionally, LTP decreased the levels of tumour necrosis factor-alpha, interferon-gamma, and interleukin-6; increased the expression of zonula occludens-1 and occludin; and reduced permeability in the jejunum of LPS-treated mice. Notably, LTP appeared to be more potent than the parental peptides LL-37 and TP5. The anti-inflammatory effects of LTP may be associated with the neutralization of LPS, inhibition of oxidative stress, and inhibition of the NF-κB signalling pathway. The findings of this study suggest that LTP might be an effective therapeutic agent for treating intestinal inflammation.
Study Information
pubmed
2019
2019-08-15T00:00:00.000Z
10.3390/ijms20163974
43
68