Kelulut honey (Heterotrigona itama) as a multi-target neuroprotective strategy against bisphenol A-induced neurotoxicity

Abstract

Bisphenol A (BPA) is a synthetic chemical widely used in the production of plastics and epoxy resins due to its low cost, durability, and heat resistance.Recognised as an endocrine-disrupting chemical, BPA has raised growing concern regarding its potential effects on brain development, particularly during prenatal and early postnatal life. BPA-induced neurotoxicity involves multiple interconnected mechanisms, including oxidative stress, neuroinflammation, mitochondrial dysfunction, synaptic impairment, and neuroendocrine disruption, which collectively contribute to cognitive and behavioural abnormalities. Kelulut honey, produced by stingless bees (Heterotrigona itama), contains various bioactive compounds such as polyphenols, flavonoids, organic acids, and trehalulose. These compounds possess antioxidant, anti-inflammatory, and neuroprotective properties and may modulate pathways involved in neuronal survival, synaptic plasticity, inflammatory regulation, NMDA receptor signalling, and estrogen-related pathways. This narrative review summarises current findings on the neuroprotective potential of kelulut honey against BPA-induced neurotoxicity, highlights existing research gaps, and discusses future directions for further mechanistic and translational studies.