Identification of the NF-κB Inhibition Peptides in Asthma from Pheretima aspergillum Decoction and Formula Granules Using Molecular Docking and Dynamics Simulations

Abstract

Background: The Pheretima aspergillum decoction is a traditional therapeutic form, while the formula granules are produced through traditional Chinese medicine decoctions. However, the active ingredients in Pheretima aspergillum have not been fully elucidated, and no published reports have investigated the differences between Pheretima aspergillum decoction and formula granules. Objective: The study aimed to explore the potential bioactive peptides in Pheretima aspergillum decoction and formula granules and investigate their potential pharmacological mechanisms in alleviating inflammation associated with asthma through interaction with the IκBβ/NF-κB p65 complex. Methods: μLC-Q Exactive MS combined with de novo sequencing technology was employed to identify potential bioactive peptides in Pheretima aspergillum decoction and formula granules. Deep learning models were utilized to evaluate the bioactivity and toxicity of these peptides. Further investigations included molecular docking studies aimed at uncovering the interactions between the selected peptides and the IκBβ/NF-κB p65 complex at affinity and critical residue sites. Molecular dynamics simulations were conducted to assess the stability of the peptide-receptor complexes. Results: A total of 2,235 peptides from the Pheretima aspergillum decoction and 1,424 peptides from the Pheretima aspergillum formula granules were identified. Deep learning models resulted in the identification of 298 bioactive and non-toxic peptides from the decoction and 145 from the formula granules. Molecular docking revealed that 160 peptides from the decoction and 63 from the formula granules exhibited a strong affinity for the IκBβ/NF-κB p65 complex. The results of molecular dynamics simulations supported the stability of the interactions involving the peptide EGPANFADLGK from the decoction and the peptide KAAVDFGVPGDAGALAHLK from the formula granules with the IκBβ/NF-κB p65 complex. In conclusion, potential bioactive peptides were identified in both Pheretima aspergillum decoction and formula granules. Conclusion: This study has investigated the potential pharmacological mechanisms of peptides derived from Pheretima aspergillum decoction and formula granules in alleviating inflammation associated with asthma through the interaction of the IκBβ/NF-κB p65 complex, providing a basis for elucidating the molecular mechanism of action for the treatment of asthma.