Isorhamnetin Attenuates Atherosclerosis by Inhibiting Macrophage Apoptosis via PI3K/AKT Activation and HO-1 Induction

被引：94
作者：
Luo, Yun [1 ,2 ]
Sun, Guibo [1 ,2 ]
Dong, Xi [3 ]
Wang, Min [1 ,2 ]
Qin, Meng [1 ,2 ]
Yu, Yingli [1 ,2 ]
Sun, Xiaobo [1 ,2 ]
机构：
[1] Chinese Acad Med Sci, Key Lab Bioact Subst & Resources Utilizat Chinese, Minist Educ, Inst Med Plant Dev, Beijing 100730, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
[3] Wenzhou Med Univ, Acad Chinese Mat Med, Wenzhou, Zhejiang, Peoples R China
来源：
PLOS ONE | 2015年 / 10卷 / 03期
关键词：
HEME OXYGENASE-1; OXIDATIVE STRESS; REACTIVE OXYGEN; CELL-DEATH; EXPRESSION; EFFEROCYTOSIS; LIPOPROTEINS; PROTECTS; PATHWAY; GENE;
D O I：
10.1371/journal.pone.0120259
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Background and Purpose Isorhamnetin (Iso) is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L. Previous studies have revealed its anti-cancer, anti-inflammatory, and antioxidant activities. This study investigated the ability of Iso to inhibit oxidized low-density lipoprotein (ox-LDL)-induced cell apoptosis in THP-1-derived macrophages. The effects of Iso on atherosclerosis in vivo were also evaluated in apolipoprotein E knockout (ApoE-/-) mice fed a high fat diet. Methods and Results Iso showed significant inhibitory effects on ox-LDL-induced THP-1-derived macrophage injuries via decreasing reactive oxygen species levels, lipid deposition, and caspase-3 activation, restoring mitochondrial membrane potential, reducing the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells, and regulating apoptosis-related proteins. We also determined the protective effects of Iso by PI3K/AKT activation and HO-1 induction. Iso reduced the atherosclerotic plaque size in vivo in ApoE-/- mice as assessed by oil red O, Sudan IV staining, and CD68-positive cells, and reduced macrophage apoptosis as assessed by caspase-3 and TUNEL assays in lesions. Conclusion In conclusion, our results show that Iso inhibited atherosclerotic plaque development in ApoE-/- mice by PI3K/AKT activation and HO-1 induction.
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页数：19
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