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Formononetin-Celecoxib Conjugate as Matrix Metalloproteinase 9 Inhibitor for Osteoarthritis Therapy

Curr Top Med Chem. 2026 Jan 9. doi: 10.2174/0115680266377273251010093254. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to synthesize and characterize the Formononetin- Celecoxib Conjugate, evaluate its efficacy both in vitro and in vivo, and ascertain its potential as a medicinal agent for osteoarthritis (OA).

METHODS: Phytoconstituents from Glycine max and FDA-approved drugs were meticulously curated and subjected to computational analyses for target identification and molecular docking. The Formononetin-Celecoxib Conjugate was subsequently synthesized and characterized using spectroscopic techniques. In vitro assessments included MTT viability assays and ELISA analyses. In vivo efficacy was evaluated using an MIA-induced OA mouse model.

RESULTS: Molecular Formononetin-Celecoxib Conjugate has high binding affinity towards MMP-9. In vitro, the conjugate was non-toxic and significantly reduced MMP-9 expression. In vivo, it attenuated paw volume (p < 0.05) and prevented body weight loss in OA-induced mice, especially at 200 mg/kg. Statistical analysis (Mean ± SD; two-way ANOVA with Tukey’s test) confirmed significant therapeutic benefits.

DISCUSSION: The study validates the conjugate’s anti-inflammatory and disease-modifying potential through both computational and experimental approaches. Its effects on MMP-9 inhibition suggest translational relevance for human OA. However, small sample size and lack of blinding remain limitations requiring further investigation.

CONCLUSION: Our study demonstrates the promising potential of the Formononetin-Celecoxib Conjugate as a novel therapeutic intervention for OA. By integrating computational predictions with experimental validations, this approach represents a step toward precision medicine in managing OA.

PMID:41568487 | DOI:10.2174/0115680266377273251010093254

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