Integrated Molecular Docking and Dynamic Simulations Reveal Glycyrrhizic Acid Alleviates Allergic Rhinitis in Rats by...

Area of Science:

• Immunology
• Pharmacology
• Computational Biology

Background:

• Allergic rhinitis (AR) is a widespread chronic inflammatory condition with limited treatment options.
• Glycyrrhizic acid (GA), derived from Glycyrrhiza uralensis, shows anti-inflammatory properties but its direct mechanism in AR is unclear.
• Key knowledge gaps exist regarding GA's binding to the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/IL-1β pathway and its therapeutic mediation in AR.

Purpose of the Study:

• To investigate the direct binding of Glycyrrhizic acid (GA) to core proteins within the TLR4/NF-κB/IL-1β inflammatory pathway.
• To validate the therapeutic effects of GA in an allergic rhinitis (AR) rat model using integrated computational and in vivo approaches.
• To elucidate the molecular mechanisms underlying GA's anti-inflammatory actions in AR.

Main Methods:

• Establishment of an ovalbumin (OVA)-induced AR rat model with intranasal GA administration.
• Utilizing molecular docking and 100 ns molecular dynamics (MD) simulations to assess GA's binding affinity and complex stability with TLR4 pathway proteins (TLR4, MyD88, NF-κB, IL-1β).
• Evaluating AR symptoms via behavioral observation, histopathology, serum cytokine analysis, immunohistochemistry, and RT-qPCR to confirm pathway modulation.

Main Results:

• GA significantly ameliorated AR symptoms, including sneezing and rhinorrhea, and reduced nasal mucosal damage in rats.
• GA restored the Th1/Th2 immune balance by modulating key cytokines and demonstrated strong binding affinity to IL-1β and TLR4.
• In vivo studies confirmed GA's downregulation of TLR4, MyD88, NF-κB, and IL-1β expression, alongside reduced pro-inflammatory cytokines.

Conclusions:

• Glycyrrhizic acid (GA) alleviates AR symptoms through direct binding to TLR4/NF-κB/IL-1β pathway proteins, inhibiting inflammation and restoring immune balance.
• The study provides robust computational and experimental evidence supporting GA as a targeted therapeutic agent for allergic rhinitis.
• GA's mechanism involves suppressing inflammatory pathway activation and modulating immune responses, highlighting its potential for AR treatment.