Femtosecond laser and bee venom as promising anti-arthritic treatments: Modulation of JAK/STAT and PI3K/AKT/mTOR signaling pathways in vivo.

Rheumatoid arthritis (RA) is a chronic condition characterized by joint degradation and systemic manifestations, which increase the risk of mortality and disability. This study compared the effects of bee venom (BV; subcutaneously administered at 1 mg/kg) and femtosecond laser irradiation (FSL; 830 nm wavelength, 200 mW power, 120 s exposure time, 0.8 cm2 beam area with a 0.5 cm radius, 0.25 W/cm2 power density, and 30 J/cm2 energy dose), either individually or in combination, on arthritic rats. Forty-two adult male Wistar rats were allocated into seven groups. Groups 1-3 served as the negative control, BV, and FSL groups, respectively, while group 4 functioned as the arthritic model group that received 100 μL/rat of complete Freund's adjuvant (CFA) in the right hind paw. Groups 5-7 included arthritic rats treated with BV, FSL, or their combination, respectively. Histological examination of RA development, showing synovitis, cellular infiltration, and cartilage degeneration. Treatment with BV injections and FSL irradiation significantly reduced right hind paw edema, improved histological abnormalities, and reduced serum levels of C-reactive protein (CRP) and rheumatoid factor (RF), alongside decreased tissue expressions of TNF-α, NF-KB, and IL-6 in the affected ankle joints. Moreover, both treatments mitigated oxidative stress, reduced DNA damage, and regulated PI3K/AKT/mTOR and JAK/STAT signaling pathways. Collectively, FSL, either alone or in combination with BV, demonstrated a superior capacity for cartilage regeneration and tissue repair. This highlights BV and FSL as a promising RA therapy, addressing underlying mechanisms beyond symptom relief.