Search

Background MicroRNAs play an important role in many fundamental biological and pathological processes. Defining the microRNAs profile underlying the processes by beneficial and detrimental lifestyles, including caloric restriction (CR), exercise and high-fat diet (HF), is necessary for understanding both normal physiology and the pathogenesis of metabolic disease. We used the microarray to detect microRNAs expression in livers from CR, EX and HF mice models. After predicted potential target genes of differentially expressed microRNAs with four algorithms, we applied GO and KEGG to analyze the function of predicted microRNA targets. Results We describe the overall microRNAs expression pattern, and identified 84 differentially expressed microRNAs changed by one or two or even all the three lifestyle modifications. The common and different enriched categories of gene function and main biochemical and signal transduction pathways were presented. Conclusions We provided for the first time a comprehensive and thorough comparison of microRNAs expression profiles in liver among these lifestyle modifications. With this knowledge, our findings provide us with an overall vision of microRNAs in the molecular impact of lifestyle on health as well as useful clues for future and thorough research of the role of microRNAs.

Nanomaterials in particular the magnetic nanoparticles (MNPs) offer tremendous potential for cancer treatment due to their unique intrinsic properties. Combining materials with a variety of functional groups, and forming a multifunctional nanosystem to overcome the limitations of monotherapy for cancer treatment has always been a research focus with notable difficulties. Considering the many challenges faced by radiotherapy and hyperthermia, in this study, we designed a rational strategy for magnetic hyperthermia using Fe

Objective. To investigate the protective effects and regulatory mechanism of miR-488-3p on doxorubicin-induced cardiotoxicity. Methods. The C57BL/6 mice and primary cardiomyocytes were used to construct doxorubicin-induced cardiomyocyte injury models in vivo and in vitro. The levels of miR-488-3p and its downstream target genes were analyzed by quantitative real-time PCR. Mouse cardiac function, cell survival, cellular injury-related proteins, and the apoptosis level of cardiomyocytes were analyzed by echocardiography, MTT analysis, Western blotting, and DNA laddering separately. Results. Cardiomyocyte injury caused by a variety of stimuli can lead to the reduction of miR-488-3p level, especially when stimulated with doxorubicin. Doxorubicin led to significant decrease in cardiac function, cell autophagic flux blockage, and apoptosis in vivo and in vitro. The expression of miR-488-3p’s target gene, CyclinG1, increased remarkably in the doxorubicin-treated neonatal mouse cardiomyocytes. Overexpression of miR-488-3p inhibited CyclinG1 expression, increased cardiomyocyte viability, and attenuated doxorubicin-induced cardiomyocyte autophagic flux blockage and apoptosis. Conclusions. miR-488-3p is one of the important protective miRNAs in doxorubicin-induced cardiotoxicity by inhibiting the expression of CyclinG1, which provides insight into the possible clinical application of miR-488-3p/CyclinG1 as therapeutic targets in doxorubicin-induced cardiovascular diseases.

Platelet hyperactivity is a risk factor for cardiovascular disease and thrombosis. Recent studies reported that the tomato extract Fruitflow inhibited platelet function, but the molecular mechanism is still unclear. The present study used proteomics to quantitatively analyze the effect of fruitflow on the inhibition of collagen-stimulated platelets and validated the involvement of several signaling molecules. Fruitflow significantly inhibited human platelet aggregation and P-selectin expression that were induced by collagen. Proteomics analysis revealed that compared fruitflow-treated collagen-stimulated platelets with only collagen-stimulated platelets, 60 proteins were upregulated and 10 proteins were downregulated. Additionally, 66 phosphorylated peptides were upregulated, whereas 37 phosphorylated peptides were downregulated. Gene Ontology analysis indicated that fruitflow treatment downregulated phosphoinositide 3-kinase (PI3K)/protein kinase B and guanosine triphosphatase-mediated signal transduction in collagen-activated platelets. Biological validation indicated that fruitflow decreased Akt, glycogen synthase kinase 3β, p38 mitogen-activated protein kinase (MAPK), and heat shock protein (Hsp27) phosphorylation in collagen-stimulated platelets. Fruitflow recovered cyclic adenosine monophosphate levels in collagen-activated platelets and reduced protein kinase A substrate phosphorylation that was induced by collagen. These findings suggest that fruitflow is a functional food that can inhibit platelet function, conferring beneficial effects for people who are at risk for platelet hyperactivity-associated thrombosis.

Background Endothelial cells are sensitive to changes in both blood components and mechanical stimuli. Endothelial cells may undergo phenotypic changes, such as changes in adhesion protein expression, under different shear stress conditions. Such changes may impact platelet and monocyte adhesion to endothelial cells. This phenomenon is linked to chronic vascular inflammation and the development of atherosclerosis. In the present study, we investigated the effects of ginkgolide B on platelet and monocyte adhesion to human umbilical vein endothelial cells (HUVECs) under different conditions of laminar shear stress. Methods Platelet and monocyte adhesion to endothelial cells was determined by the Bioflux 1000. HUVECs were incubated with ginkgolide B or aspirin for 12 h, and then TNFα was added for 2 h to induce the inflammatory response under conditions of 1 and 9 dyn/cm2 laminar shear stress. The protein expression was analyzed by Western blot. Results The number of platelets that adhered was greater under conditions of 1 dyn/cm2 than under conditions of 9 dyn/cm2 of laminar shear stress (74.8 ± 19.2 and 59.5 ± 15.1, respectively). Ginkgolide B reduced the tumor necrosis factor α (TNFα)-induced increase in platelet and monocyte adhesion to HUVECs at 1 and 9 dyn/cm2 of laminar shear stress. In TNFα-treated HUVECs, the number of monocytes that adhered was greater under conditions of 1 dyn/cm2 of laminar shear stress compared with 9 dyn/cm2 (29.1 ± 4.9 and 22.7 ± 3.7, respectively). Ginkgolide B inhibited the TNFα-induced expression of vascular cell adhesion molecule-1(VCAM-1), VE-cadherin, and Cx43 in HUVECs at 1 and 9 dyn/cm2. The expression of these proteins was not different between 1 and 9 dyn/cm2. Conclusions Ginkgolide B suppressed platelet and monocyte adhesion under different conditions of laminar shear stress. Moreover, ginkgolide B reduced VCAM-1, VE-cadherin and Cx43 expression in TNFα-treated HUVECs under laminar shear stress. This suggested that ginkgolide B might shed light on the treatment of inflammation in atherosclerosis.

Tremella fuciformis polysaccharide (TFPS), which is the extract of Tremella fuciformis Berk, has previously been demonstrated to exhibit potent anti-oxidative, anti-inflammatory and anti-aging effects. However, the mechanisms underlying these protective and therapeutic effects remain to be elucidated. The aim of the present study was to investigate the protective effects of TFPS on hydrogen peroxide-induced injury of human skin fibroblasts and to elucidate the aforementioned underlying mechanisms. A hydrogen peroxide-induced human skin fibroblast injury model was firstly established. MTT and reactive oxygen species (ROS) production assays, in addition to terminal deoxynucleotidyl transferase dUTP nick end labeling, reverse transcription-quantitative polymerase chain reaction and western blotting, were performed to investigate the protective effects of TFPS. Hydrogen peroxide decreased human skin fibroblast viability with a concurrent increase in ROS generation and cell apoptosis. Treatment with 0–400 µg/ml TFPS alone for up to 48 h did not result in alteration in cell viability. Notably, TFPS pre-treatment reduced oxidative stress and cell apoptosis in hydrogen peroxide-treated skin fibroblasts. In addition, there was profound inhibition of p16, p21, p53 and caspase-3 expression, and activation of extracellular-signal regulated kinase and Akt serine/threonine kinase 1, following TFPS pre-treatment. Furthermore, it was revealed that TFPS additionally protected fibroblasts via the upregulation of SIRT1 expression, and this was abrogated by the SIRT1 inhibitor niacinamide. These results indicated that TFPS alleviated hydrogen peroxide-induced oxidative stress and apoptosis in skin fibroblasts via upregulation of SIRT1 expression, indicating that TFPS may act as a potential therapeutic agent for oxidative-stress-associated skin diseases and aging.

Background Body posture is a fundamental indicator for assessing health and quality of life, especially for elderly people. Deciphering the changes in body posture occurring with age is a current topic in the field of geriatrics. The aims of this study were to assess the parameters of standing body posture in the global sagittal plane and to determine the dynamics of changes in standing body posture occurring with age and differences between men and women. Methods The measurements were performed on 226 individuals between the ages of 20 to 89 with a new photogrammetry, via which we assessed five postural angles - neck, thorax, waist, hip and knee. The data were analyzed with t-test, one-way ANOVA, linear regression model and generalized additive model. Results Among these segments studied here, neck changed most, while the middle segments of the body, waist and hip, were relative stable. Significant differences between men and women were found with respect to the angles of neck, thorax and hip. Three of the five postural angles were significantly influenced with aging, including increasing cervical lordosis, thoracic kyphosis and knee flexion, starting from no older than around 50 yrs. showed by fitting curve derived with generalized additive model. These changes were more marked among women. Besides, this study highlights the effects of age and gender on the complex interrelation between adjacent body segments in standing. Conclusions The presented results showed changes in the parameters describing body posture throughout consecutive ages and emphasized that for an individualized functional analysis, it is essential to consider age-and gender-specific changes in the neck, thorax and knee. This paper presents useful externally generalizable information not only for clinical purposes but also to inform further research on larger numbers of subjects. Electronic supplementary material The online version of this article (10.1186/s12877-019-1096-0) contains supplementary material, which is available to authorized users.

Aim Resveratrol is a natural plant polyphenol. The present study investigated the effects of resveratrol on the Toll-like receptor 4- (TLR4-) mediated expression and secretion of matrix metalloproteinases (MMPs) in oxidized low-density lipoprotein- (ox-LDL-) treated human umbilical vein endothelial cells (HUVECs). Methods Protein expression was analyzed by immunoblotting. The secretion of MMPs was measured by an enzyme-linked immunosorbent assay. The animal experiments were performed with and without resveratrol treatment in high-fat chow-fed mice. Results Resveratrol inhibited the expression of TLR4, MMP3, and MMP9 in ox-LDL- and lipopolysaccharide- (LPS-) treated HUVECs. Resveratrol reduced the secretion of MMP3 and MMP9 that was induced by ox-LDL and LPS. The TLR4 inhibitor CLI-095 similarly suppressed the expression and secretion of MMP3 and MMP9 in ox-LDL- and LPS-treated HUVECs. Resveratrol attenuated the phosphorylation of the transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) that was induced by ox-LDL and LPS. Resveratrol recovered Sirt1 expression. In the animal experiments, resveratrol decreased TLR4 expression in the aorta, MMP9 levels in plasma, and vascular structural changes in high-fat chow-fed mice, with no significant effect on plasma MMP3 levels. Conclusion Resveratrol inhibited the TLR4-mediated expression and secretion of MMP3 and MMP9 in ox-LDL-treated HUVECs. The mechanism of action of resveratrol may be associated with the suppression of NF-κB and STAT3 phosphorylation and restoration of Sirt1 expression. Resveratrol exerts protective effects against vascular structural changes in high-fat chow-fed mice.

Aim. Resveratrol is a natural plant polyphenol. The present study investigated the effects of resveratrol on the Toll-like receptor 4- (TLR4-) mediated expression and secretion of matrix metalloproteinases (MMPs) in oxidized low-density lipoprotein- (ox-LDL-) treated human umbilical vein endothelial cells (HUVECs). Methods. Protein expression was analyzed by immunoblotting. The secretion of MMPs was measured by an enzyme-linked immunosorbent assay. The animal experiments were performed with and without resveratrol treatment in high-fat chow-fed mice. Results. Resveratrol inhibited the expression of TLR4, MMP3, and MMP9 in ox-LDL- and lipopolysaccharide- (LPS-) treated HUVECs. Resveratrol reduced the secretion of MMP3 and MMP9 that was induced by ox-LDL and LPS. The TLR4 inhibitor CLI-095 similarly suppressed the expression and secretion of MMP3 and MMP9 in ox-LDL- and LPS-treated HUVECs. Resveratrol attenuated the phosphorylation of the transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) that was induced by ox-LDL and LPS. Resveratrol recovered Sirt1 expression. In the animal experiments, resveratrol decreased TLR4 expression in the aorta, MMP9 levels in plasma, and vascular structural changes in high-fat chow-fed mice, with no significant effect on plasma MMP3 levels. Conclusion. Resveratrol inhibited the TLR4-mediated expression and secretion of MMP3 and MMP9 in ox-LDL-treated HUVECs. The mechanism of action of resveratrol may be associated with the suppression of NF-κB and STAT3 phosphorylation and restoration of Sirt1 expression. Resveratrol exerts protective effects against vascular structural changes in high-fat chow-fed mice.

// Yuan Cao 1 , Tao Shen 1 , Xiuqing Huang 1 , Yajun Lin 1 , Beidong Chen 1 , Jing Pang 1 , Guoping Li 1 , Que Wang 1 , Sylvia Zohrabian 2 , Chao Duan 3 , Yang Ruan 4 , Yong Man 1 , Shu Wang 1 , Jian Li 1 1 Peking University Fifth School of Clinical Medicine, The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, China 2 Department of Cardiology, Boston Children’s Hospital, Enders 1250, Boston, MA, 02115, US 3 Beijing Key Laboratory of Plant Resources Research and Development, Beijing Technology and Business University, Beijing 100037, China 4 Beijing Anzhen Hospital, Capital Medical University and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China Correspondence to: Tao Shen, email: shentao4189@bjhmoh.cn Jian Li, email: lijian@bjhmoh.cn Keywords: astragalus polysaccharide, doxorubicin, cardiomyocyte, autophagy, AMPK/mTOR Received: August 20, 2016 Accepted: November 08, 2016 Published: November 25, 2016 ABSTRACT Doxorubicin (adriamycin), an anthracycline antibiotic, is commonly used to treat many types of solid and hematological malignancies. Unfortunately, clinical usage of doxorubicin is limited due to the associated acute and chronic cardiotoxicity. Previous studies demonstrated that Astragalus polysaccharide (APS), the extracts of Astragalus membranaceus , had strong anti-tumor activities and anti-inflammatory effects. However, whether APS could mitigate chemotherapy-induced cardiotoxicity is unclear thus far. We used a doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart failure model to explore the function of APS. GFP-LC3 adenovirus-mediated autophagic vesicle assays, GFP and RFP tandemly tagged LC3 (tfLC3) assays and Western blot analyses were performed to analyze the cell function and cell signaling changes following APS treatment in cardiomyocytes. First, doxorubicin treatment led to C57BL/6J mouse heart failure and increased cardiomyocyte apoptosis, with a disturbed cell autophagic flux. Second, APS restored autophagy in doxorubicin-treated primary neonatal rat ventricular myocytes and in the doxorubicin-induced heart failure mouse model. Third, APS attenuated doxorubicin-induced heart injury by regulating the AMPK/mTOR pathway. The mTOR inhibitor rapamycin significantly abrogated the protective effect of APS. These results suggest that doxorubicin could induce heart failure by disturbing cardiomyocyte autophagic flux, which may cause excessive cell apoptosis. APS could restore normal autophagic flux, ameliorating doxorubicin-induced cardiotoxicity by regulating the AMPK/mTOR pathway.

Aim. To investigate the effect of ginkgolide B on junction proteins and the reduction of monocyte migration in oxidized low-density lipoprotein- (ox-LDL-) treated endothelial cells.Methods. Human umbilical vein endothelial cells (HUVECs) were used in the present study. Immunofluorescence and Western blot were performed to determine the expression of junctional adhesion molecule-A (JAM-A), connexin 43 (Cx43), and vascular endothelial cadherin (VE-cadherin). Monocyte migration was detected by the Transwell assay.Results. ox-LDL stimulation increased JAM-A expression by 35%, Cx43 expression by 24%, and VE-cadherin expression by 37% in HUVECs. Ginkgolide B (0.2, 0.4, and 0.6 mg/mL) dose-dependently abolished the expression of these junction proteins. The monocyte transmigration experiments showed that the level of monocyte migration was sixfold higher in the ox-LDL-treated group than in the control group. Ginkgolide B (0.6 mg/mL) nearly completely abolished monocyte migration. Both ginkgolide B and LY294002 suppressed Akt phosphorylation and the expression of these junction proteins in ox-LDL-treated endothelial cells. These results suggest that the ginkgolide B-induced inhibition of junction protein expression is associated with blockade of the PI3K/Akt pathway.Conclusion. Ginkgolide B suppressed junction protein expression and reduced monocyte transmigration that was induced by ox-LDL. Ginkgolide B may improve vascular permeability in atherosclerosis.

Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) is a routine method for gene expression analysis, and reliable results depend on proper normalization by stable reference genes. Caloric restriction (CR) is a robust lifestyle intervention to slow aging and delay onset of age-associated diseases via inducing global changes in gene expression. Reliable normalization of RT-qPCR data becomes crucial in CR studies. In this study, the expression stability of 12 candidate reference genes were evaluated in inguinal white adipose tissue (iWAT), skeletal muscle (Sk.M) and liver of CR mice by using three algorithms, geNorm, NormFinder, and Bestkeeper. Our results showed β2m, Ppia and Hmbs as the most stable genes in iWAT, Sk.M and liver, respectively. Moreover, two reference genes were sufficient to normalize RT-qPCR data in each tissue and the suitable pair of reference genes was β2m-Hprt in iWAT, Ppia-Gusb in Sk.M and Hmbs-β2m in liver. By contrast, the least stable gene in iWAT or Sk.M was Gapdh, and in liver was Pgk1. Furthermore, the expression of Leptin and Ppar-γ were profiled in these tissues to validate the selected reference genes. Our data provided a basis for gene expression analysis in future CR studies.

To know whether thioredoxin 1 (Trx1) works for an antioxidant defense mechanism in atherosclerosis, the effect of Trx1 on the release of monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for recruitment and accumulation of monocytes/macrophages in the intima of artery vessel, was investigated in human endothelial-like EA.hy 926 cells. It was found that overexpression of Trx1 suppressed, whereas knockdown of endogenous Trx1 enhanced, oxidized low-density lipoprotein (oxLDL)-stimulated MCP-1 release and expression in the cells. It was also observed that overexpression of Trx1 suppressed, whereas depletion of endogenous Trx1 greatly promoted, nuclear translocation of c-Jun and the redox factor-1 (Ref-1). Electrophoretic mobility shift assay showed significantly reduced DNA-binding activity of activator protein-1 (AP-1) in Trx1-overexpressing cells but apparently enhanced DNA binding activity of AP-1 in Trx1-knockdown cells, indicating that nuclear Ref-1 rather than Trx1 itself finally dominates the regulation of AP-1 activity, although Trx1 is considered to upregulate AP-1 activity. It was also observed that Trx1 depressed intracellular generation of reactive oxygen species (ROS). Diphenyleneiodonium (DPI), the inhibitor of NADPH oxidase, suppressed MCP-1 secretion, whereas transient expression of Nox1 enhanced transcription of MCP-1 in endothelial cells. Assays with AP-1 and MCP-1 luciferase reporters further demonstrated that transient expression of Trx1 significantly depressed the transcriptional activity of c-Jun/c-Fos and consequent MCP-1 transcription. This study suggests that Trx1 inherently suppresses MCP-1 expression in vascular endothelium and may prevent atherosclerosis by depressing MCP-1 release. Besides the suppression of intracellular ROS generation, the inhibition of nuclear translocation of AP-1 and Ref-1 are mainly responsible for the downregulation of MCP-1 by Trx1.

Oxidized low-density lipoprotein (ox-LDL) is an important risk factor in the development of atherosclerosis. LOX-1, a lectin-like receptor for ox-LDL, is present primarily on endothelial cells and upregulated by ox-LDL, tumor necrosis factor a, shear stress, and cytokines in atherosclerosis. Recent studies demonstrated that ginkgolide B, a platelet-activating factor receptor antagonist, has antiinflammatory and antioxidant effects on endothelial and nerve cells. The present study investigated the effects of ginkgolide B on LOX-1 expression and the possible mechanism of action. Our results showed that ginkgolide B inhibited LOX-1 and intercellular cell adhesion molecule-1 (ICAM-1) expression in ox-LDL-stimulated endothelial cells through a mechanism associated with the attenuation of Akt activation. Similar data were obtained by silencing Akt and LY294002. We also evaluated Sirt1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. These molecules play a protective role in endothelial cell injury. The results showed that ginkgolide B increased Sirt1 expression in ox-LDL-treated cells. The inhibitory effects of ginkgolide B on LOX-1 and ICAM-1 expression were reduced in Sirt1 siRNA-transfected cells. Nrf2 expression was increased in ox-LDL-treated cells, and ginkgolide B downregulated Nrf2 expression. These results suggest that ginkgolide B reduces Nrf2 expression by inhibiting LOX-1 expression, consequently reducing oxidative stress injury in ox-LDL-stimulated cells. Altogether, these results indicate that the protective effect of ginkgolide B on endothelial cells may be attributable to a decrease in LOX-1 expression and an increase in Sirt1 expression in ox-LDL-stimulated endothelial cells, the mechanism of which is linked to the inhibition of Akt activation. Ginkgolide B may be a multiple-target drug that exerts protective effects in ox-LDL-treated human umbilical vein endothelial cells.

Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.

Atherosclerosis is a chronic inflammation disease that is initiated by endothelial cell injury. Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. To understand whether thioredoxin1 (Trx1) participates in an antiinflammatory defense mechanism in atherosclerosis, we investigated the effect of Trx1 on the expression of two adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in human umbilical vein endothelial cells (HUVECs). Thioredoxin1 and dominant-negative mutant thioredoxin1 (TD) were transiently overexpressed using adenovirus vector gene transfer. Our data showed that Trx1 overexpression suppressed ox-LDL-induced adhesion molecule expression in HUVECs. The overexpression of Trx1 promoted ox-LDL-induced Smad3 phosphorylation and nuclear translocation. A co-immunoprecipitation assay indicated that Smad3 continued to interact with Trx1 with or without ox-LDL stimulation. These results suggest that Trx1 inherently suppresses VCAM-1 and ICAM-1 expression in vascular endothelia and may prevent the initiation of atherosclerosis by attenuating adhesion molecule expression. The enhancement of Smad3 phosphorylation and nuclear expression appears to be primarily responsible for the Trx1-induced downregulation of adhesion molecules.

Aims To investigate whether ginkgolide B (a platelet-activating factor inhibitor) affects vascular inflammation in atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) mice. Methods and Results Human platelets were used to evaluate the effects of ginkgolide B on platelet aggregation and signal transduction. Ginkgolide B attenuated platelet aggregation and inhibited phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in thrombin- and collagen-activated platelets. ApoE−/− mice were administered a high-cholesterol diet for 8 weeks. Plasma platelet factor 4 (PF4) and RANTES (regulated upon activation, normal T-cell expressed, and secreted protein) were then measured using an enzyme-linked immunosorbent assay. Scanning electron microscopy and immunohistochemistry were used to determine atherosclerotic lesions. Ginkgolide B decreased plasma PF4 and RANTES levels in ApoE−/− mice. Scanning electron microscopic examination showed that ginkgolide B reduced aortic plaque in ApoE−/− mice. Immunohistochemistry analysis demonstrated that ginkgolide B diminished P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE−/− mice. Moreover, ginkgolide B suppressed macrophage and vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE−/− mice. Similar effects were observed in aspirin-treated ApoE−/− mice. Conclusion Ginkgolide B significantly reduced atherosclerotic lesions and P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE−/− mice. The efficacy of ginkgolide B was similar to aspirin. These results provide direct evidence that ginkgolide B inhibits atherosclerosis, which may be associated with inhibition of the PI3K/Akt pathway in activated platelets.