Therapeutic potential of infrared-treated bee venom: enhanced multi-faceted bioactivity via compositional modulation

Natural products are rich therapeutic sources, yet their translation into effective medicines remains challenging. Bee venom (BV) contains a diverse repertoire of bioactive molecules, but gentle, scalable methods to enhance its functionality are limited. This study, therefore, investigates a novel, solvent-free, post-extraction infrared (IR) conditioning step to fine-tune BV's composition and bioactivity. BV was irradiated (230 V, 50 Hz, 150 W) and compared to native extract using GC-MS and bioactivity assays. GC-MS revealed selective compositional tuning, with significant enrichment (p ≤ 0.05) of 4H-1-benzopyran-4-one, 2-(3,4-dimethoxyphenyl)-3,5-dihydroxy-7-methoxy. IR-treated BV exhibited enhanced antimicrobial activity, with increased zones of inhibition for Staphylococcus aureus (15 ± 0.1 vs. 11 ± 0.4 mm), Bacillus subtilis (24 ± 0.2 vs. 22 ± 0.6 mm), Candida albicans (26 ± 0.1 vs. 22 ± 0.5 mm), Klebsiella pneumoniae (24 ± 0.4 vs. 15 ± 0.3 mm), and Salmonella typhi (27 ± 0.8 vs. 20 ± 0.7 mm). MICs decreased for S. aureus, B. subtilis, and K. pneumoniae. The treated BV also showed stronger antibiofilm activity at 25% MBC concentrations for K. pneumoniae and S. typhi (p ≤ 0.05) and significantly reduced hemolysis at 25% MIC for S. aureus and B. subtilis (p ≤ 0.05). Antioxidant capacity increased (DPPH IC₅₀: 16.47 ± 1.1 vs. 27.65 ± 0.8 µg/mL), as did anti-inflammatory activity (COX-2 IC₅₀: 48.84 ± 0.2 vs. 50.99 ± 0.9 µg/mL; COX-1 IC₅₀: 24.7 ± 0.2 vs. 41.74 ± 0.2 µg/mL). Cytotoxicity against PC-3 and SKOV-3 cells was maintained (IC₅₀: 19.73 ± 0.9 and 19.76 ± 0.11 µg/mL, respectively, vs. native BV's 11.48 ± 0.3 and 17.46 ± 0.27 µg/mL). These findings establish brief IR irradiation as a practical, scalable post-processing strategy to selectively enhance the therapeutic potential of BV for biomedical applications.