Abstract
Aicao ( Artemisia argyi ) and honey are herbal medicines for the regulation of digestion and various major diseases driven by compounds, but the effect of processing-generated particles remains elusive. Our aim is to investigate the Aicao/Honey (AC/H) complex-particle formation and to test whether different hydrothermal synthesis temperatures produce particles with distinct physicochemical and biological properties that contribute to cytotoxicity via known or novel pathways. For methods, we processed AC/H complexes at 150℃ and 200℃ and investigated characteristics as potential honey-infused or carbon-dot-like synthesis with imaging potential. The nanoparticles are approximately 100 nm or smaller in size, possess negatively charged surfaces and red fluorescence, and can enter the Golgi apparatus within cells. The two synthesized AC/Hs exhibit a distinct degree of regulation of peroxidase activities, cytotoxicity, and nanozyme (herbzyme) of phosphatase enhancement, which is linked to promoting AKT kinase inhibitor efficiency with targeting AKT phosphorylation at Ser473 but not Thr308 or decreased AKT levels. Consistently, the compound-target enrichment analysis suggests the AC/H in targeting the PI3K/AKT pathway and potent compound docking. Importantly, the AC/H-induced cytotoxicity was disrupted by the ferroptosis inhibitor Fer-1 and abolished upon ROS inhibition by NAC, while the AC/H stimulated ROS production and regulated ferroptosis-associated GPX4. Thus, the different temperature-processed AC/H requires ROS and ferroptosis for inducing cytotoxicity, with phosphatase-like enhancing activity for targeting phosphorylation in cancer cell death. Our studies highlight the particle effect of AC/H by different hydrothermal processing with potential applications in pharmaceuticals or biomedicine as a non-food industrial use.