Notoginsenoside R1 Alleviates Macrophage Inflammatory Responses via Modulating the JAK1/STAT3 Pathway

Notoginsenoside R1 (NR1), an active component of Panax notoginseng, may exert anti-atherosclerotic effects by modulating macrophage M1/M2 polarization. This study aimed to investigate the specific mechanism of NR1 against atherosclerosis based on the JAK1/STAT3 pathway. M1 and M2 macrophage models, as well as an ox-LDL-induced macrophage model, were established. These models were treated with varying concentrations of NR1. Our results demonstrated that NR1 effectively suppressed LPS/IFN-γ or ox-LDL-induced polarization of macrophages toward the pro-inflammatory M1 phenotype and promoted their transition to the anti-inflammatory M2 phenotype. Concurrently, NR1 significantly inhibited the phagocytosis of ox-LDL by macrophages in the atherosclerosis model, reduced lipid accumulation, and improved mitochondrial function. Mechanistically, the regulatory effects of NR1 on macrophage polarization and function primarily depended on the inhibition of the JAK1/STAT3 signaling pathway. In conclusion, this study suggests that NR1 targets the JAK1/STAT3 pathway to balance macrophage M1/M2 polarization, thereby suppressing inflammatory responses, and ultimately alleviating atherosclerosis.