FLEXA, a new herbal formulation, alleviates inflammation and cartilage degradation of osteoarthritis by inhibiting the activation of the MAPK/ NF-κB signaling pathways

Abstract

Background

Osteoarthritis (OA) is a progressive musculoskeletal disorder marked by cartilage degradation and inflammation. FLEXA, a novel herbal formulation composed of Ostericum koreanum Maxim, Cibotium barometz J. Smith, and Carthamus tinctorius Linne, has traditionally been used to manage joint-related conditions. This study aimed to evaluate the therapeutic efficacy of FLEXA in an OA model by elucidating its molecular mechanisms and multi-target effects.

Methods

Network pharmacology analysis was performed to identify potential interactions between the active components of FLEXA and OA-related targets. Osteoarthritis was induced in rats via intra-articular injection of monosodium iodoacetate (MIA), followed by intramuscular administration of FLEXA at two doses (0.0094 and 0.094 mg/kg) twice weekly for four weeks. Cartilage integrity, proteoglycan content, bone mineral density, and inflammatory markers were assessed. Additionally, the effects of FLEXA on mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways were evaluated in interleukin-1β-stimulated SW1353 chondrocytes.

Results

FLEXA improved cartilage integrity, increased proteoglycan levels, and enhanced bone mineral density in the femoral condyles of OA rats. Network pharmacology revealed that FLEXA modulated key targets associated with “Positive Regulation of Extracellular Matrix Assembly”. In SW1353 cells, FLEXA suppressed MAPK and NF-κB signaling, reducing pro-inflammatory cytokine production and extracellular matrix degradation.

Conclusion

These findings demonstrate that FLEXA exerts multi-target chondroprotective and anti-inflammatory effects, suggesting its potential as a complementary therapeutic option for OA management.