In silico Screening of Duhaldea nervosa-derived Endogenous Peptides to Predict the Potential Anticancer Mechanisms

D. nervosa is a wild perennial herb used in traditional Chinese medicine for treating fractures, rheumatoid arthritis, and digestive disorders. Its primary bioactive components are flavonoids, phenolic acids, and sesquiterpenes. However, bioactive peptides, which exhibit a wide range of biological activities and are commonly found in both animals and plants, have not been reported in D. nervosa to date. To investigate the presence and potential bioactivities of bioactive peptides in D. nervosa, the abundance of endogenous peptides was initially analyzed using a Nano-LC-Q Exactive Plus quadrupole Orbitrap mass spectrometer. Subsequently, bioinformatics screening, computational enzyme hydrolysis, "target-pathway-disease" network prediction, molecular docking, and molecular dynamics simulations were performed to evaluate safety, biological activity prediction and investigate the potential anticancer mechanisms of D. nervosa. The results demonstrate that the simulated enzymatic hydrolysates of D. nervosa endogenous peptide target and bind to cancer pathway receptor proteins such as MMP9, MAPK1, SRC, and PI3KCA, indicating their potential anticancer activity. This study provides valuable information for further research and the development of novel anti-cancer drugs.