Discovery of Anti-inflammatory Peptides from Channa argus Using Virtual Screening, Molecular Docking, and Cell Model

The purpose of this study was to screen potential anti-inflammatory peptides from Channa argus. Toll-like receptor (TLR)2 and TLR4 were chosen as the target proteins. Virtual hydrolysis was used to select the best enzyme for obtaining bioactive peptides from C. argus proteins. Anti-inflammatory peptides were selected by the combined use of physicochemical prediction, molecular docking, and a cell model, and their mechanisms of action were elucidated. The results showed that 109 bioactive peptides obtained with papain were not toxic, from which 34 highly water-soluble peptides were selected for analysis of adsorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Peptides KF, PR, NC, YR, WEL, QWWR and DEECWF exhibited high-affinity binding to TRL2 and TRL4 mainly through hydrogen bonding. These peptides were found to increase cell viability and inhibit the overproduction of nitric oxide (NO) and inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating their anti-inflammatory activity. This study revealed the interaction mechanism between the anti-inflammatory peptides and TLR2 or TLR4 targets and provides theoretical support for understanding the mechanism underlying the immunoregulatory effect of bioactive peptides from C. argus.