Hydroxysafflor yellow A attenuates microcirculatory disturbance in MAFLD via the EGFR/MAPK1 pathway.

The incidence of metabolic-associated fatty liver disease (MAFLD) continues to rise, making it a leading cause of chronic liver disease worldwide. Its pathological progression is frequently accompanied by microcirculatory dysfunction. However, effective therapeutic interventions targeting this specific process remain limited. Hydroxysafflor yellow A (HSYA) is the primary active component of Carthamus tinctorius L. It exerts diverse pharmacological effects, including anti-inflammatory, antioxidant, and microcirculation-improving activities. However, the specific mechanisms by which HSYA regulates microcirculatory dysfunction in MAFLD have yet to be elucidated. In this study, a rat model of MAFLD was established using a methionine choline-deficient (MCD) diet to investigate the protective effects of HSYA and the underlying EGFR/MAPK1 signaling mechanism. The results showed that HSYA treatment significantly reduced serum levels of ALT, AST, TC, TG, and ET-1, while increasing NO levels. HSYA administration also expanded mesenteric microvascular diameter and accelerated blood flow velocity. Furthermore, HSYA alleviated hepatic steatosis and inflammatory injury. These effects were accompanied by the downregulation of EGFR, MAPK1, and VEGF expressions in the liver, thereby inhibiting the overactivation of the EGFR/MAPK1 pathway. In summary, HSYA effectively ameliorates hepatic injury and microcirculatory dysfunction in MAFLD rats. The underlying mechanism is associated with inhibiting the overactivation of the EGFR/MAPK1 signaling pathway and downregulating VEGF expression, which collectively restores the balance of microvascular structure and function. These findings provide experimental evidence for the therapeutic potential of HSYA in treating MAFLD-related microcirculatory disorders.