A novel kefir exopolysaccharides (KEPS) derived from kefir grain fermentation were found to have a small molecular weight (12 kDa) compared to the traditionally high molecular weight (12,000 kDa) of kefiran (KE). KE has been shown to possess antioxidant, blood pressure-lowering, and immune-modulating effects. In this study, we characterized KEPS and KE and evaluated their anti-inflammatory properties in vitro using RAW264.7 macrophages. The main monosaccharide components were identified as glucose (98.1 ± 0.06%) in KEPS and galactose (45.36 ± 0.16%) and glucose (47.13 ± 0.06%) in KE, respectively. Both KEPS and KE significantly reduced IL-6 secretion in lipopolysaccharide (LPS)-stimulated macrophages. We further investigated their effects in LPS-induced systemic injury in male and female NF-κB-luciferase^+/+ transgenic mice. Mice received oral KEPS (100 mg/kg) or KE (100 mg/kg) for seven days, followed by LPS or saline injection. KEPS and KE inhibited NF-κB signaling, as indicated by reduced luciferase expression and phosphorylated NF-κB levels. LPS-induced systemic injury increased luciferase signals, especially in the kidney, spleen, pancreas, lung, and gut tissues of female mice compared to male mice. Additionally, it upregulated inflammatory mediators in these organs. However, KEPS and KE effectively suppressed the expression of inflammatory mediators, including p-MAPK and IL-6. These findings demonstrate that KEPS can alleviate LPS-induced systemic damage by inhibiting NF-κB/MAPK signaling, suggesting their potential as a treatment for inflammatory disorders.

Lactoferrin (LF)-derived peptides (LDPs) are short cationic and amphipathic fragments generated primarily from the N-terminal lobe of LF through pepsin-mediated proteolytic processes. The best-characterized LDPs include lactoferricin (LFcin), lactoferrampin (LFampin), and LF1-11. In addition to these native peptides, a growing range of engineered LDPs has been developed by modifying the LFcin-derived RRWQWR motif through the incorporation of non-natural amino acids, cyclization, multimerization, and conjugation with chemotherapeutic agents. LDPs have garnered significant interest as potential anticancer peptides due to their ability to preferentially engage with the surfaces of malignant cells and initiate various tumor-suppressive mechanisms. This review article provides an overview of the principal classes of LDPs and elucidates how structural features influence membrane interaction, selectivity, intracellular targeting, apoptotic pathways, and immune modulation. It also discusses current mechanistic insights and examines the major challenges and opportunities for translating innovative LDPs into clinically useful cancer therapeutics.