Biochanin A attenuates zymosan-induced arthritis in mice similarly to 17-β estradiol: an alternative to hormone replacement therapy?

Objective and design: Biochanin A (BCA), a phytoestrogen, has various pharmacological properties. This study was conducted to compare BCA's therapeutic property against 17-β estradiol replacement therapy in zymosan-induced arthritis (ZIA) in mice. Additionally, we further investigated in vitro the anti-inflammatory action on neutrophils.

Treatment: Ovariectomized (OVX) and non-OVX mice were pretreated with BCA (1, 3 and 9 mg/kg) or estrogen (50 µg/kg) for 14 days prior to ZIA. Neutrophils were pretreated with BCA (1, 10 and 100 μM) for 1 h prior to phorbol 12-myristate 13-acetate.

Methods: Anti-inflammatory effects of BCA were evaluated by cellular infiltrate, paw edema and cytokine measurement. In vitro, apoptosis was assessed by morphology and flow cytometry. Neutrophil extracellular traps (NET) were determined by fluorescent microscopy and DNA release. Statistical differences were determined by one- or two-way ANOVA.

Results: BCA inhibited neutrophil accumulation, paw edema and proinflammatory cytokine (TNF-α and IFN-γ) and increased anti-inflammatory cytokines (IL-4 and IL-10) in OVX and non-OVX mice, similar to 17-β estradiol replacement therapy. In vitro, BCA increased apoptosis and consequently reduced NETs.

Conclusion: BCA has a notable anti-inflammatory effect, similar to 17-β estradiol, and is especially effective for treatment of ZIA. These results suggest that BCA may be promising for the treatment of postmenopausal arthritis.

Keywords: 17-β estradiol; Arthritis; Biochanin A; Hormone replacement therapy; Neutrophils; Phytoestrogens.