Mechanism of San Jie Tong Mai Fang in Atherosclerosis Attenuation by JAK/STAT-mediated Inhibition of Macrophage M1 Polarization

Macrophage polarization influences the atherosclerotic plaque microenvironment by driving inflammatory responses, with the JAK/STAT signaling pathway serving as a critical regulator of this process. This study investigated whether San Jie Tong Mai Fang (SJTMF), an herbal formulation reported to promote M2-type macrophage polarization, alleviates atherosclerosis (AS) by modulating the JAK/STAT signaling pathway. An AS model was established in apoE^-/- mice via 12-week high-fat diet feeding, followed by 4-week treatment with SJTMF alone or combined with a JAK Inhibitor or macrophage scavenger. Our findings demonstrated that SJTMF significantly attenuated atherosclerotic plaque formation in apoE^-/- mice, concomitant with improved blood lipid metabolism and inflammatory levels. We also observed that the expression of Arginase-1 (Arg-1) and interleukin-10 (IL-10) was upregulated by SJTMF, whereas the expression of inducible Nitric Oxide Synthase (iNOS) and interleukin-1beta (Il-1β) was downregulated in the aortic tissues of apoE^-/- mice. Notably, the effect of SJTMF increased with co-administration of JAK inhibitors (decreased p-JAK2 and p-STAT3 levels, p < 0.01), whereas it was significantly inhibited by the combination with macrophage scavengers. Our results demonstrated that SJTMF may contribute to inhibiting AS by modulating M1-type polarization of macrophages, thereby attenuating inflammation; this effect may occur through suppression of the JAK/STAT signaling pathway.