Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Abstract

Atherosclerosis-related cardiovascular disease is still the predominant cause of death worldwide. Araloside C (AsC), a natural saponin, exerts extensive anti-inflammatory properties. In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/-mouse model and RAW264.7 macrophages exposed to ox-LDL, AsC was evaluated for its effects on polarization and autophagy. AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in ox-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methyladenine and BECN1 siRNA obviously abolished the antiatherosclerotic and M2 macrophage polarization effects of AsC. Mechanistically, AsC targeted Sirt1and increased its expression, and this increase in expression was associated with increased autophagy and M2 phenotype polarization. In contrast, the effects of AsC were markedly blocked by EX527 and Sirt1 siRNA. Altogether, AsC attenuates foam cell formation and lessens atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy.

Ginsenoside Compound K Attenuates Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation via Autophagy Induction and Modulating NF-κB, p38, and JNK MAPK Signaling

“…As shown in Figure 1B , treatment with CK less than 2.5 μg/ml did not influence cell viability. Based on the previous study ( Luo et al, 2020 ), we used 80 µg/ml ox-LDL to induce the formation of foam cells in this study. According to oil red O results ( Figures 1C, D ), lipid accumulation was increased by ox-LDL, whereas it was decreased in the group treated with CK at different concentrations.…”

“…Moderate autophagy can inhibit the formation and development of atherosclerotic plaques. Our previous studies have demonstrated that macrophage autophagy can reduce the formation of foam cells and the secretion of inflammatory factors and promote the transformation of macrophages to the M2 phenotype (Luo et al, 2020). In addition, the genetic knockout of the key autophagy gene Atg5 can significantly inhibit cholesterol leakage and promote the formation of foam cells (Singh et al, 2009).…”

“…The cells were seeded into various plates and pretreated with different concentrations of CK for 12 h with or without the MAPK activator, anisomycin (0.1 μM) or the autophagy inhibitor 3-MA (5 mM). Then cells were stimulated with 80 μg/ml ox-LDL for 24 h. The dosage for CK and ox-LDL was chosen based on previous pharmacodynamics studies ( Lu et al, 2019 ; Luo et al, 2020 ).…”

“…Macrophages Oil red O staining was conducted based the method usd in our latest study (Luo et al, 2020). RAW264.7 cells were cultured in 24-well sterile culture plates at 5×10 4 cells/well.…”

“…Macrophage autophagosome detection was performed by using TEM, in accordance with previous report (Luo et al, 2020). Briefly, RAW264.7 cells were seeded into 6-well sterile culture plates at 1×10 6 cells/well.…”