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Combination of Isoliquiritigenin and Vancomycin Alleviates Staphylococcus aureus-Induced Bone Infection in Rats
Mingbo Wang1, Huicheng Lv1, Long Han2
1Trauma Surgery Section B, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
|September 24, 2025
Summary
Vancomycin (VAN) combined with isoliquiritigenin (ISL) effectively treats Staphylococcus aureus osteomyelitis. This combination therapy reduces infection severity, inflammation, and bacterial load while promoting bone repair.
Area of Science:
- Orthopedics
- Infectious Diseases
- Pharmacology
Background:
- Osteomyelitis caused by Staphylococcus aureus presents significant treatment challenges due to rising antibiotic resistance.
- Isoliquiritigenin (ISL), a chalcone derived from licorice, possesses known antibacterial and anti-inflammatory properties.
- Methicillin-resistant Staphylococcus aureus (MRSA) infections, particularly implant-related osteomyelitis, require novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of vancomycin (VAN) combined with ISL against MRSA-induced implant-related osteomyelitis in a rat model.
- To investigate the synergistic effects of VAN and ISL on infection severity, inflammation, bacterial load, and bone repair.
- To explore the in vitro mechanisms of ISL in modulating inflammatory responses and promoting osteogenesis in osteoblasts.
Main Methods:
- A rat model of MRSA-induced tibial osteomyelitis with Kirschner wire implantation was established.
- Rats were treated with VAN (50 mg/kg), ISL (100 mg/kg), or the combination therapy for 14 days.
- In vitro studies assessed ISL's effects on MRSA-infected MC3T3-E1 osteoblasts, analyzing inflammatory signaling pathways (NF-κB, MAPK) and osteogenic markers (Runx2, BMP2, ALP, mineralization).
Main Results:
- Combined VAN + ISL therapy significantly reduced bone infection severity and histopathological scores compared to monotherapies (p < 0.001).
- The combination therapy markedly decreased serum inflammatory markers (IL-6, TNF-α, IL-1β, CRP) and bacterial loads in bone/wire (p < 0.001).
- In vitro, ISL suppressed MRSA-induced inflammation by inhibiting NF-κB and MAPK signaling and promoted osteogenesis by activating BMP/Smad signaling and enhancing mineralization.
Conclusions:
- Vancomycin and isoliquiritigenin combination therapy demonstrates superior efficacy over monotherapy for MRSA-induced osteomyelitis.
- The synergistic approach concurrently eradicates bacteria, mitigates inflammation, and stimulates bone repair.
- This combination therapy represents a promising strategy for managing recalcitrant implant-related osteomyelitis.
