ZHANG Zi-wen,LI Chen-chen,PAN Rui-le,et al.Proteomic-based studies on hypolipidemic mechanism of total phenylpropanoid glycosides from Ligustrum robustum(Roxb.) Blume in hyperlipidemic hamsters[J].Chinese Pharmacological Bulletin,2019,(08):1126-1133.[doi:10.3969/j.issn.1001-1978.2019.08.018]





Proteomic-based studies on hypolipidemic mechanism of total phenylpropanoid glycosides from Ligustrum robustum(Roxb.) Blume in hyperlipidemic hamsters
张紫文12李晨晨2潘瑞乐2孙 乐2杨润梅2陈爱兵1高南南2
1.河北科技大学化学与制药工程学院,河北 石家庄 050018; 2.中国医学科学院北京协和医学院药用植物研究所中草药物质基础与资源利用教育部重点实验室&中药(天然药物)创新药物研发北京市重点实验室,北京 100193
ZHANG Zi-wen12 LI Chen-chen2 PAN Rui-le2 SUN Le2 YANG Run-mei2 CHEN Ai-bing1 GAO Nan-nan2
1.College of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050018,China; 2.Key Lab of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences,Peking Union Medical College, Beijing 100193, China
粗壮女贞总苷 金黄地鼠 高脂血症 label-free蛋白质组学 生物信息学分析 调脂机制
total phenylpropanoid glycosides from Ligustrum robustum(Roxb.)Blume hamsters hyperlipidemia label-free quantitative proteomics bioinformatics analysis hypolipidemic mechanism
R-332; R284.1; R341; R349.31; R589.2; R977.6
目的 应用非标记定量(label-free)蛋白质组学技术,探究粗壮女贞总苷(LRTPG)的调脂机制。方法 从高脂血症模型组和LRTPG给药组金黄地鼠肝脏中提取总蛋白,进行label-free蛋白质组学研究。结果 蛋白质组学研究共鉴定出2 231个蛋白质,模型组与LRTPG组共549个差异表达蛋白,其中93种蛋白上调,59种蛋白下调,397种蛋白只在模型组或者给药组中有定量值。GO分析表明,这些差异表达蛋白主要参与代谢、转运、氧化还原、磷酸化、信号转导、脂质代谢等生物学过程。KEGG通路分析表明,这些蛋白集中于氧化磷酸化、非酒精性脂肪肝病、PI3K-Akt、cAMP、cGMP-PKG等多条信号通路。一些差异蛋白与脂质代谢密切相关,包括CD36、PK、HSS、GCK、ApoA I、Acly、FABP5等。结论 LRTPG调脂作用可能与CD36、PK、HSS、GCK、ApoA I、Acly、FABP5有关。
Aim To explore the hypolipidemic mechanism of the total phenylpropanoid glycoside from Ligustrum robustum(Roxb.)Blume(LRTPG)on hyperlipidemic hamsters using label-free quantitative proteomic technique.Methods The total protein was extracted from livers of model group and the group treated with LRTPG for label-free quantitative proteomics research.Results The proteomic data showed that a total of 2231 proteins were identified.And 549 proteins were found to be differentially expressed between model group and group treated with LRTPG.Among the 549 proteins, 93 proteins were up-regulated and 59 proteins were down-regulated, and 397 proteins had quantitative values only in model group or drug-administered group.Further, gene ontology(GO)analysis indicated that those differentially expressed proteins were primarily involved in an array of biological processes including metabolism, transport, oxidation-reduction, phosphorylation, signal transduction and lipid metabolism.KEGG pathway analysis revealed that these proteins were involved in several signal pathways including oxidative phosphorylation, non-alcoholic fatty liver dis-ease, PI3K-Akt, cAMP, and cGMP-PKG pathway.And some of these proteins were much related to the lipid metabolism, such as CD36, PK, HSS, GCK, ApoA I, Acly and FABP5.Conclusion The hypolipidemic effect of LRTPG may be related to CD36, PK, HSS, GCK, ApoA I, Acly and FABP5.


[1] Zoungas S, Curtis A J, McNeil J J, et al.Treatment of dyslipidemia and cardiovascular outcomes:the journey so far——is this the end for statins[J]? Clin Pharmacol Ther,2014,96(2):192-205.
[2] 孙 乐,贺震旦,杨润梅,等.粗壮女贞总苷降脂作用及其基于AMPK通路的降脂作用机制研究[J].中国药理学通报,2017,33(8):1073-9.
[2] Sun L, He Z D, Yang R M, et al.Hypolipidemic activity of total phenylpropanoid glycosides from Ligustrum robustum(Roxb)Blume and its mechanisms on AMPK pathway[J].Chin Pharmacol Bull,2017,33(8):1073-9.
[3] Yang R M, Chu X X, Sun L, et al.Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides from Ligustrum robustum(Roxb.) Blume by AMPK-SREBP-1c pathway in hamsters fed a high-fat diet[J].Phytother Res,2018,32(4):715-22.
[4] Yang R M, Liu F, He Z D, et al.Anti-obesity effect of total phenylpropanoid glycosides from Ligustrum robustum Blume in fatty diet-fed mice via up-regulating leptin[J].J Ethnopharmacol,2015,169:459-65.
[5] ParK Y M, Febbraio M, Silverstein R L.CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to mecrophage trapping in the arterial intima[J].J Clin Invest,2009,119(1):136-45.
[6] Gribilas G, Zarros A, Zira A, et al.Involvement of hepatic stimulator substance in experimentally induced fibrosis and cirrhosis in the rat[J].Dig Dis Sci,2009,54(11):2367-76.
[7] 黄 卉,申竹芳.以葡萄糖激酶为靶点的抗糖尿病新药研究[J].中国药理学通报, 2006,22(9):1025-9.
[7] Hang H, Shen Z F.The research of the glucokinase target for the treatment of diabetes[J].Chin Pharmacol Bull,2006,22(9):1025-9.
[8] Ikenaga M, Higaki Y, Saku K, et al.High-density lipoprotein mimetics:a therapeutic tool for atherosclerotic diseases[J].J Atheroscler Thromb,2016,23(4):385-94.
[9] Wakil S J, Abu-Elheiga L A.Fatty acid metabolism:target for metabolic syndrome[J].J Lipid Res,2009,50(Suppl):S 138-43.
[10] Dallaqlio K, Marconi A, Truzzi F, et al.E-FABP induces differentiation in normal human keratinocytes and modulates the differentiation process in psoriatic keratinocytes in vitro[J].Exp Dermatol,2013,22(4):255-61.
[11] Hofer P, Boeszoermenyi A, Jaeger D, et al.Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58 Linking Lipolysis with Lipid Ligand Shuttling[J].J Biol Chem, 2015,290(30):18438-53.
[12] Zhang Z, Wang W, Jin L, et al.iTRAQ-based quantitative proteomics analysis of the protetive effect of Yinchenwuling powder on hyperlipidemic rats[J].Evid Based Complement Alternat Med,2017,2017:1-12.
[13] Zhou L H, Xu J Y, Dai C, et al.Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactor II as potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula[J].Chin J Nat Med,2018, 16(4):241-51.
[14] 秦 佑,杨瑞仪,陈梅果,等.树豆酮酸A抑制3T3-L1细胞脂肪合成与分解的作用研究[J].中国药理学通报,2016,32(2):189-93.
[14] Qin Y, Yang R Y, Chen M G, et al.Inhibitory effect of cajanonic acid A on lipogenesis and lipolysis in 3T3-L1 adipocytes[J].Chin Pharmacol Bull,2016,32(2):189-93.
[15] Furuhashi M, Tuncman G, Görgün C Z, et al.Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2[J].Nature,2007, 447(7147):959-65.
[16] Pinkosky S L, Filippov S, Srivastava R A, et al.AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism[J].J Lipid Res,2013,54(1):134-51.
[17] Jiang S J, Li W, An W.Adenoviral gene transfer of hepatic stimulator substance confers resistance against hepatic ischemia–reperfusion injury by improving mitochondrial function[J].Hum Gene Ther,2013,24(4):443-56.
[18] Gordts S C, Muthuramu I, Nefyodova E, et al.Beneficial effects of selective HDL-raising gene transfer on survival, cardiac remodelling and cardiac function after myocardial infarction in mice[J].Gene Ther,2013,20(11):1053-61.


[1]孙 乐,贺震旦,杨润梅,等.粗壮女贞总苷降脂作用及其基于AMPK通路的降脂作用机制研究[J].中国药理学通报,2017,(08):1073.[doi:10.3969/j.issn.1001-1978.2017.08.008]
 SUN Le,HE Zhen-dan,YANG Run-mei,et al.Hypolipidemic activity of total phenylpropanoid glycosides from Ligustrum robustum(Roxb.)Blume and its mechanisms on AMPK pathway[J].Chinese Pharmacological Bulletin,2017,(08):1073.[doi:10.3969/j.issn.1001-1978.2017.08.008]


基金项目:国家自然科学基金青年基金项目(No 81703746); 北京协和医学院青年科研基金资助项目(No 3332015142)
更新日期/Last Update: 2019-08-14