Amygdalin Attenuates Atherosclerosis and Plays an Anti-Inflammatory Role in ApoE Knock-Out Mice and Bone Marrow-Derived Macrophages
Yiru Wang, Qingyun Jia, Yifan Zhang, Jing Wei, Ping Liu
Abstract
Amygdalin, the main component of Prunus persica (L.) Stokes, has been used to treat atherosclerosis in mouse model due to its anti-inflammatory role. However, the exact mechanism underlying its protective property remains poorly understood. This study aimed to evidence the influence of amygdalin on high-fat diet induced atherosclerosis in ApoE knock-out (ApoE-/-) mice, and unravel its anti-inflammatory mechanism. ApoE-/- mice fed with HFD for eight weeks were randomly divided into four groups and injected with amygdalin at the concentration of 0.08 mg/ kg or 0.04 mg/ kg for twelve weeks. Additionally, bone marrow-derived macrophages were intervened with oxidized low-density lipoprotein (oxLDL) or lipopolysaccharide plus various concentrations of amygdalin for further exploration. Body weight, serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-PCR, plaque sizes by Oil Red O, lymphatic vessels of heart atrium and TNF- production by immunofluorescence staining. MAPKs, AP-1 and NF-B p65 pathways were also explored. Amygdalin decreased ApoE-/- mice body weight, serum lipids, plaque size, lymphatic vessels and inflammatory cytokines (IL-6, TNF-), NO and iNOS, and increased IL-10 expression. In oxLDL-induced bone marrow-derived macrophages, amygdalin reduced inflammatory cytokines (IL-6, TNF-), NO and iNOS, and increased IL-10 production. These effects were associated with the decrease of phosphorylated ERK1/2, JNK, p38, c-Fos and c-Jun, and the translocation of NF-B p65 from nucleus to cytoplasm. These results suggested that amygdalin could attenuate atherosclerosis and play an anti-inflammatory role via MAPKs, AP-1 and NF-B p65 signaling pathways in ApoE-/- mice and oxLDL-treated bone marrow-derived macrophages.