Deciphering the Distinct Vascular Liver Injury Induced by Pyrrolizidine Alkaloids: From the Invasive Species to Health Hazard

Pyrrolizidine alkaloids (PAs) are the most common plant-derived toxins present in numerous herbal and food products, but their environmental transfer pathways and toxicological mechanisms remain unclear. This study establishes a complete contamination pathway from environmental source to molecular target. We identified the invasive plant Bidens alba as a novel PA producer and provided the first evidence of transfer to honey by detecting corresponding PAs and characteristic Bidens alba pollens in local samples. Mechanistically, we demonstrated that PA toxicity fundamentally differs from classic hepatotoxins like acetaminophen. Instead of directly damaging liver cells, PAs first induce red blood cell rupture (hemolysis) by selectively inhibiting glucose-6-phosphate dehydrogenase (G6PD). This hemolytic event precedes observable liver sinusoidal endothelial damage and initiates characteristic vascular liver injury. Our findings establish a new route of food contamination and redefine PA toxicity by identifying blood cells as the primary target, with significant implications for food safety and public health.