title: Cryptotanshinone, an orally bioactive herbal compound from Danshen, attenuates atherosclerosis in apolipoprotein E-deficient mice: role of lectin-like oxidized LDL receptor-1 (LOX-1).
abstract: OBJECTIVE
  Cryptotanshinone (CTS) is a major bioactive diterpenoid isolated from Danshen, an eminent medicinal herb that is used to treat cardiovascular disorders in Asian medicine. However, it is not known whether CTS can prevent experimental atherosclerosis. The present study was designed to investigate the protective effects of CTS on atherosclerosis and its molecular mechanisms of action.
  
  
  METHODS
  Apolipoprotein E-deficient (ApoE(-/-)) mice, fed an atherogenic diet, were dosed daily with CTS (15, 45 mg kg(-1) day(-1)) by oral gavage. In vitro studies were carried out in oxidized LDL (oxLDL)-stimulated HUVECs treated with or without CTS.
  
  
  RESULTS
  CTS significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in ApoE(-/-) mice by inhibiting the expression of lectin-like oxLDL receptor-1 (LOX-1) and MMP-9, as well as inhibiting reactive oxygen species (ROS) generation and NF-κB activation. CTS treatment significantly decreased the levels of serum pro-inflammatory mediators without altering the serum lipid profile. In vitro, CTS decreased oxLDL-induced LOX-1 mRNA and protein expression and, thereby, inhibited LOX-1-mediated adhesion of monocytes to HUVECs, by reducing the expression of adhesion molecules (intracellular adhesion molecule 1 and vascular cellular adhesion molecule 1). Furthermore, CTS inhibited NADPH oxidase subunit 4 (NOX4)-mediated ROS generation and consequent activation of NF-κB in HUVECs.
  
  
  CONCLUSIONS
  CTS was shown to have anti-atherosclerotic activity, which was mediated through inhibition of the LOX-1-mediated signalling pathway. This suggests that CTS is a vasculoprotective drug that has potential therapeutic value for the clinical treatment of atherosclerotic cardiovascular diseases.
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.|Drug Discovery Center, School of Chemical Biology and Biotechnology (SCBB), Shenzhen Graduate School of Peking University, Shenzhen, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.|Aab Cardiovascular Research Institute, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
authors.forename: Suowen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Changhua
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Aab Cardiovascular Research Institute, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
authors.forename: Zheng-Gen
authors.initials: ZG
authors.lastname: Jin
authors.affiliation: Department of Pharmacology and Toxicology, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of Construction Foundation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010616:Phenanthrenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001057:Apolipoproteins E; D004365:Drugs, Chinese Herbal; C495138:Olr1 protein, mouse; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; C037886:cryptotanshinone