Bee venom in pharmacology: Mechanistic insights from pro-inflammatory trigger to anti-inflammatory therapeutic agent.

Bee venom (BV) is inherently toxic, traditionally recognized for provoking pain, edema, and hypersensitivity via components such as melittin and bee venom-derived phospholipase A₂ (bvPLA₂). Paradoxically, these same peptides exhibit potent anti-inflammatory and immunomodulatory activities when administered in carefully controlled doses or optimized formulations. Preclinical studies, as summarized across multiple disease models, consistently demonstrate suppression of pro-inflammatory cytokines, inhibition of NF-κB signaling, modulation of T-cell and macrophage responses, and enhancement of antioxidant defenses. Early clinical evidence further suggests potential benefits in rheumatoid arthritis, multiple sclerosis, and inflammatory skin disorders. Nonetheless, BV's allergenic and cytotoxic properties highlight the urgent need for standardized preparations and advanced delivery strategies, such as nanocarriers and microneedle systems, to improve stability, safety, and therapeutic precision. Together, these findings underscore the dual-edged nature of BV, positioning it not merely as a pro-inflammatory toxin but as a candidate anti-inflammatory and immunomodulatory therapy with translational potential.