Title:Identification of the NF-κB Inhibition Peptides in Asthma from Pheretima
aspergillum Decoction and Formula Granules using Molecular Docking
and Dynamics Simulations
Volume: 20
Issue: 3
Author(s): Xiaotong Xiao, Yaxiong Liu*, Yayang Huang, Wenjie Zeng and Zhuoya Luo*
Affiliation:
- NMPA Key
Laboratory of Rapid Drug Inspection Technology, Guangdong Institute For Drug Control, Guangdong Biomedical
Technology Collaborative Innovation Center, Guangdong Institute For Drug Control, Guangzhou, 510663, P.R. China
- NMPA Key
Laboratory of Rapid Drug Inspection Technology, Guangdong Institute For Drug Control, Guangdong Biomedical
Technology Collaborative Innovation Center, Guangdong Institute For Drug Control, Guangzhou, 510663, P.R. China
Keywords:
Pheretima aspergillum decoction, Pheretima aspergillum formula granules, bioactive peptides, asthma, NF-κB, μLC-Q Exactive MS.
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 IκBα/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.
