Amygdalin and Cyanogenic Stress: Linking Plant Defense, Redox Signaling, and Xenochemical Toxicity

Amygdalin is a cyanogenic diglycoside whose hydrolysis links plant defense with cyanide exposure in animals and humans. This review examines its activation, metabolism and associated stress responses. In intact plant tissues, cyanogenic glycosides are separated from hydrolytic enzymes; tissue disruption permits substrate-enzyme contact. Amygdalin hydrolysis produces prunasin and mandelonitrile, followed by benzaldehyde and hydrogen cyanide (HCN). After oral exposure, host and microbial β-glucosidases contribute to activation, while host and potentially microbial detoxification modify cyanide exposure. The biological response depends on dose, release rate, exposure route, detoxification capacity and mitochondrial susceptibility. Localized HCN production participates in plant stress signaling, whereas excessive exposure inhibits mitochondrial respiration and may lead to secondary oxidative and inflammatory injury. Mammalian cell studies have reported low-level regulatory effects, but these findings do not establish therapeutic benefit from oral amygdalin. Reports of antioxidant or anti-inflammatory activity require measurements of cyanogenic activation to distinguish responses to the parent glycoside from those associated with its degradation. Time-resolved measurements of amygdalin and its products of biotransformation should be paired with microbial, mitochondrial and redox endpoints and appropriate experimental controls.