Monotropein mitigates atherosclerotic plaque vulnerability through circ_0140736/miR-495/SIRPα-mediated efferocytosis.

Efferocytosis is a biological process in which phagocytic cells engulf and degrade senescent, damaged, or dead cells to prevent secondary necrosis and inflammation. This process is implicated in various diseases, including atherosclerosis (AS). Enhancing efferocytosis efficiency may offer a promising therapeutic strategy for managing AS. Consequently, increasing attention is being paid to pharmacological agents that can promote efferocytosis. Monotropein (MON), the predominant iridoid glycoside in Morinda officinalis, has demonstrated anti-inflammatory and analgesic properties in previous studies. However, its role in regulating atherosclerotic plaque stability remains unclear. In this study, we show that MON enhances plaque stability in AS. The expression of circ_0140736 was found to be elevated in unstable atherosclerotic plaques. MON suppressed circ_0140736 expression and alleviated miR-495 sequestration via a competing endogenous RNA mechanism, thereby increasing miR-495 levels and downregulating signal regulatory protein α (SIRPɑ) expression. In conclusion, MON exerts its anti-atherosclerotic effects by promoting efferocytosis through the circ_0140736/miR-495/SIRPɑ axis, suggesting its potential as a promising therapeutic candidate for AS.