Bioactive secretory leukocyte protease inhibitor (SLPI)-derived short peptides (SDSPs) attenuate LPS-induced inflammatory responses in macrophages

Inflammation is a crucial defence mechanism against infections and harmful stimuli. However, uncontrolled inflammation can lead to low-grade inflammatory conditions that disrupt tissues and systemic function. Anti-inflammatories relieve symptoms. However, it can cause side effects and lack targeted control. These limitations are addressed by “peptide-based therapeutics.” The secretory leukocyte protease inhibitor (SLPI) has anti-inflammatory effects. However, SLPI has a short half-life and low cellular uptake. Using short peptides is a promising therapeutic strategy due to their small size, high effectiveness, and low immunogenicity. This research investigates the anti-inflammatory effect of SLPI-derived short peptides (SDSPs). SLPI was enzymatically digested in silico to produce SDSPs. The physiological properties of SDSPs and their anti-inflammatory activities in an LPS-induced RAW 264.7 cell inflammatory model were examined. Digested fragments, including 11 from pepsin (P1-11) and 9 from trypsin (T1-T9) digestion, plus the N-terminal fragment, were obtained. SDSPs are diverse physiological properties, and some are anti-inflammatory peptides (AIPs). Determination in the LPS-induced macrophage inflammation model found four potential SDSPs, specifically T6, T7, T8, and P7, exhibit anti-inflammatory properties by reducing excessive ROS generation and the activation of the MAPK/NF-κB pathway, similar to SLPI. This study identifies possible candidates for anti-inflammatory medicines warranting further investigation in in vivo and clinical trials for inflammation-related disorders.