Cathelicidin-BF antimicrobial peptide

The pathogenesis of ulcerative colitis (UC) is associated with severe inflammation, damaged colonic barriers, increased oxidative stress, and intestinal dysbiosis. The majority of current medications strive to alleviate inflammation but fail to target additional disease pathologies. Addressing multiple symptoms using a single 'magic bullet' remains a challenge. To overcome this, a smart epigallocatechin-3-gallate (EGCG)-loaded silk fibroin-based nanoparticle (NP) with the surface functionalization of antimicrobial peptides (Cathelicidin-BF, CBF) was constructed, which could be internalized by Colon-26 cells and RAW 264.7 macrophages with high efficiencies. The resulting CBF-EGCG-NPs efficiently restored colonic epithelial barriers by relieving oxidative stress and promoting epithelium migration. They also alleviated immune responses through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and lipopolysaccharide (LPS) elimination. Interestingly, oral administration of hydrogel (chitosan/alginate)-embedding CBF-EGCG-NPs could not only retard progression and treat UC, but also modulate intestinal microbiota by increasing their overall diversity and richness and augmenting the abundance of beneficial bacteria (e.g., Firmicutes and Lactobacillaceae). Our work provides a "many birds with one stone" strategy for addressing UC symptoms using a single NP-based oral platform that targets immune microenvironment modulation, LPS clearance, and microbial remodeling.

Intestinal barrier functions are altered during the development of sepsis. Cathelicidin antimicrobial peptides, such as LL-37 and mCRAMP, can protect animals against intestinal barrier dysfunction. Cathelicidin-BF (C-BF), a new cathelicidin peptide purified from the venom of the snake Bungarus fasciatus, has been shown to have both antimicrobial and anti-inflammatory properties. This study investigated whether C-BF pretreatment could protect the intestinal barrier against dysfunction in a mouse model of endotoxemia, induced by intraperitoneal injection of LPS (10mg/kg). Mice were treated with low or high dose C-BF before treatment with LPS, and samples were collected 5h after LPS treatment. C-BF reduced LPS induced intestinal histological damage and gut permeability to 4 KD Fluorescein-isothiocyanate-conjugated dextran. Pretreatment with C-BF prevented LPS induced intestinal tight junction disruption and epithelial cell apoptosis. Moreover, C-BF down regulated the expression and secretion of TNF-α, a process involving the NF-κB signaling pathway. C-BF also reduced LPS induced TNF-α expression through the NF-κB signaling pathway in mouse RAW 264.7 macrophages. These findings indicate that C-BF can prevent gut barrier dysfunction induced by LPS, suggesting that C-BF may be used to develop a prophylactic agent for intestinal injury in endotoxemia.

The objective was to evaluate the effects of antimicrobial peptide cathelicidin-BF (C-BF) treatment on diarrhea controlling, immune responses, intestinal inflammation, and intestinal barrier function in piglets with postweaning diarrhea. In this study, fifty-four weaned piglets with diarrhea were selected and treated with saline (control), C-BF or norfloxacin nicotinic (NFN) for 7 days. Here, we investigated the effects of C-BF on diarrhea controlling, growth performance, serum immune indicators, intestinal morphology, intestinal inflammation, and intestinal epithelial barrier function in the weaned piglets with diarrhea. The results showed that C-BF treatment decreased (P < 0.05) diarrheal index and increased (P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI) compared with control group. C-BF treatment decreased (P < 0.05) levels of serum blood urea nitrogen (BUN) and aspartate aminotransferase (AST), but increased (P < 0.05) levels of serum A/G and alkaline phosphatase (ALP) compared with control group. The concentrations of IL-6, IL-8, tumor necrosis factor-α (TNF-α), and IgG were lower (P < 0.05), but IgA was greater (P < 0.05) for piglets treated by C-BF compared with those in control group. C-BF and NFN treatment decreased (P < 0.05) IL-6, IL-8, IL-22, IL-10 and transforming growth factor-β (TGF-β) production in the jejunum and ileum compared with the control group. C-BF treatment increased the expression levels of zonula occluden-1 (ZO-1), Occludin, and Claudin-1 in the jejunum and colon compared with the control group and the NFN group. In conclusion, these data indicate that C-BF treatment may be an effective therapeutic strategy for controlling post-weaning diarrhea, improving immune responses, attenuating intestinal inflammation and enhancing intestinal barrier function in piglets with postweaning diarrhea.