title: Elatoside C protects against ox-LDL-induced HUVECs injury by FoxO1-mediated autophagy induction.
abstract: The vascular endothelial cell injury induced by oxidized low-density lipoprotein (ox-LDL) is a major contributing factor to the pathogenesis of atherosclerosis. Elatoside C (EsC), a natural saponin isolated from Longya Aralia chinensis L., possesses anti-oxidative activity; however, there is still no report indicating that EsC protects against ox-LDL-induced endothelial cell injury and the exact mechanisms of this protection. Recently, autophagy has attracted extensive attention on the basis of its ability to modulate cell survival. Thus, we determined the role of autophagy in the protective effects of EsC against ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Our results demonstrated that EsC pretreatment reduced ox-LDL-induced HUVECs oxidative injury, increased the number of autophagosomes and modulated the expression of autophagy related proteins. Moreover, autophagy inhibitor 3-methyladenine, chloroquine and BECN1 siRNA obviously abolished the anti-oxidative effects of EsC. Furthermore, our data indicated that EsC significantly increased nuclear FoxO1 expression level and FoxO1 siRNA markedly attenuated the protective effects of EsC. In conclusion, EsC attenuated ox-LDL-induced HUVECs injury by inducing autophagy via increasing FoxO1 expression level. EsC is thus considered as a potential drug for the treatment of atherosclerosis.
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China.
authors.forename: Xiangbao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Qin
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China. Electronic address: sunguibo@126.com.
authors.forename: Guibo
authors.initials: G
authors.lastname: Sun
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China; Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, China. Electronic address: sunpapersubmit@sina.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D008077:Lipoproteins, LDL; D012503:Saponins; C000601129:elatoside C; C099252:oxidized low density lipoprotein
keywords: Apoptosis; Autophagy; Elatoside C; FoxO1; HUVECs; Ox-LDL