A highly efficient hybrid peptide ameliorates intestinal inflammation and mucosal barrier damage by neutralizing lipopolysaccharides and antagonizing the lipopolysaccharide‐receptor interaction

Abstract

Intestinal inflammatory disorders, such as inflammatory bowel disease, are major contributors to mortality and morbidity in humans and animals worldwide. While some native peptides have great potential as therapeutic agents against intestinal inflammation, potential cytotoxicity, anti-inciting action, and suppression of antiinflammatory activity may limit their development as anti-inflammatory agents. Peptide hybridization is an effective approach for the design and engineering of novel functional peptides because hybrid peptides combine the advantages and benefits of various native peptides. In the present study, a novel hybrid anti-inflammatory peptide that combines the active center of Cecropin A (C) and the core functional region of LL-37 (L) was designed [C-L peptide; C (1-8)-L (17-30)] through in silico analysis to reduce cytotoxicity and improve the anti-inflammatory activity of the parental peptides. The resulting C-L peptide exhibited lower cytotoxicity than either C or L peptides alone. C-L also exerted a protective effect against lipopolysaccharide (LPS)induced inflammatory responses in RAW264.7 macrophages and in the intestines of a mouse model. The hybrid peptide exhibited increased anti-inflammatory activity compared to the parental peptides. C-L plays a role in protecting intestinal tissue from damage, LPS-induced weight loss, and leukocyte infiltration. In addition, C-L reduces the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 2 | WEI Et al.

Hydroxysafflor yellow A protects against ulcerative colitis via suppressing TLR4/NF‐κB signaling pathway

“…LPS is a strong pro‐inflammatory factor that may be closely related to the occurrence and development of UC (Rosillo et al, 2015). Studies also confirmed that LPS can induce RAW 264.7 cells to secrete pro‐inflammatory cytokines (Hwang et al, 2016), thereby destroying the intestinal mucosal barrier, and ultimately leading to the continuous development of inflammation (Wei et al, 2020). Based on the above studies, we investigated the effect of HSYA on DSS‐induced UC in rats and LPS–induced UC in RAW 264.7 cells.…”

Mechanisms of action of anti-inflammatory proteins and peptides with anti-TNF-alpha activity and their effects on the intestinal barrier: A systematic review

“…Another hybrid peptide containing the functional core region of LL-37 was evaluated by Wei et al [ 11 ], this time hybridized with the active center of cecropin A (C), called peptide C-L. This hybrid also exerted a protective effect against LPS-induced intestinal inflammation, protecting the intestinal tissue from damage by reducing leukocyte infiltration, inflammatory cytokine concentrations and cell apoptosis.…”

“…Several preclinical studies with models of intestinal inflammation aimed to understand the mechanisms of action of these anti-inflammatory proteins and peptides that reduce TNF-α. Such studies describe the mechanisms involved in the action of these molecules to develop the best strategies for treating these diseases [10][11][12]. Therefore, this systematic review aimed to study the mechanisms of action of these proteins and peptides and their effects on the inflamed intestinal barrier in animal models.…”

Anti-Inflammation and Protective Effects of Anethum graveolens L. (Dill Seeds) on Esophageal Mucosa Damages in Reflux Esophagitis-Induced Rats

“…The LPS-induced macrophage RAW264.7 inflammatory model is commonly used to detect the anti-inflammatory activity of natural drugs [28,29]. RWA264.7 cells are also being used to research gastrointestinal mucosal damage and anti-inflammation mechanisms [30,31].…”