ROS-Dependent Activation of Autophagy through the PI3K/Akt/mTOR Pathway Is Induced by Hydroxysafflor Yellow A-Sonodynamic Therapy in THP-1 Macrophages

Monocyte-derived macrophages participate in infaust inflammatory responses by secreting various types of proinflammatory factors, resulting in further inflammatory reactions in atherosclerotic plaques. Autophagy plays an important role in inhibiting inflammation; thus, increasing autophagy may be a therapeutic strategy for atherosclerosis. In the present study, hydroxysafflor yellowA-mediated sonodynamic therapywas used to induce autophagy and inhibit inflammation inTHP-1macrophages. Following hydroxysafflor yellow A-mediated sonodynamic therapy, autophagy was induced as shown by the conversion of LC3-II/LC3-I, increased expression of beclin 1, degradation of p62, and the formation of autophagic vacuoles. In addition, inflammatory factors were inhibited. These effects were blocked by Atg5 siRNA, the autophagy inhibitor 3-methyladenine, and the reactive oxygen species scavenger N-acetyl cysteine. Moreover, AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 decreased significantly afterHSYA-SDT. These effectswere inhibited by the PI3K inhibitor LY294002, theAKT inhibitor triciribine, themTOR inhibitor rapamycin, mTORsiRNA, andN-acetyl cysteine. Our results demonstrate thatHSYA-SDTinduces an autophagic response via the PI3K/Akt/mTOR signaling pathway and inhibits inflammation by reactive oxygen species in THP-1 macrophages.