Pharmacological Effects and Molecular Mechanisms of Bee Venom: Recent Evidence from Experimental and Preclinical Studies

Bee venom (BV) is a complex natural secretion produced by female honeybees for defensive purposes, comprising peptides, enzymes, biogenic amines, amino acids, carbohydrates, pheromones, and various minerals. Among its constituents, melittin, phospholipase A2 (PLA₂), and apamin are particularly notable for their pharmacological relevance. This review summarizes studies published between 2020 and 2025, highlighting the anti-inflammatory, antinociceptive, neuroprotective, and anticancer properties of BV. BV and its bioactive components exert diverse biological effects through the modulation of apoptosis, autophagy, oxidative stress pathways, and ion channel activity. Melittin and PLA₂ act synergistically to disrupt cellular membrane integrity and inhibit key signaling cascades, including PI3K/Akt, MAPK, and NF-κB, thereby inducing selective cytotoxicity in cancer cells. The neuroprotective effects of BV are associated with the regulation of Nrf2/HO-1 and TrkB/CREB/BDNF pathways, as well as the maintenance of Ca²⁺ homeostasis, ultimately supporting neuronal survival and cognitive function. In models of inflammation and arthritis, BV reduces oxidative stress and alleviates tissue damage by suppressing the production of pro-inflammatory cytokines. Overall, these findings underscore the multifaceted pharmacological potential of BV; however, further mechanistic investigations and well-designed clinical studies are required to comprehensively establish its efficacy and safety.