Fig. 3
Schematic representation of the role of NAD(P)H oxidase (NOX) in DOX-induced cardiomyopathy. DOX upregulates NOX2 and NOX4 expression by activating the angiotensin receptor, oxidizes NADPH, and reduces O2 to produce ROS. On the one hand, ROS causes oxidative stress and DNA damage, further activates MAPK-mediated apoptosi. On the other hand, ROS activates Drp1, inducing mitochondrial division, causing NLRP3-mediated apoptosis and eventually causing myocardial damage. Natural compounds including neferine (N), valsartan (V), necrostain-1 (N-1), setanaxib (S), astragaloside (AS), acacia (A), irisin (I), NSC23766 (NS) and resolvin D1 (R) attenuated DOX-induced cardiomyopathy by downregulation of NOX2 and NOX4. DOX: doxorubicin, Drp1: motility-related protein 1, MAPK: mitogen-activated protein kinases, NLRP3: nucleotide- binding domain-like receptor protein 3, ROS: reactive oxygen species. (By Figdraw.)