title: The anti-atherosclerotic effect of tanshinone IIA is associated with the inhibition of TNF-α-induced VCAM-1, ICAM-1 and CX3CL1 expression.
abstract: Tanshinone IIA is one of the major diterpenes in Salvia miltiorrhiza. The inhibitory effect of Tanshinone IIA on atherosclerosis has been reported, but the underlying mechanism is not fully understood. The present study aimed to study the anti-atherosclerosis effect of Tanshinone IIA on the adhesion of monocytes to vascular endothelial cells and related mechanism. Results showed that Tanshinone IIA, at the concentrations without cytotoxic effect, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated human vascular endothelial cells. The expressions of cell adhesion molecules including VCAM-1, ICAM-1 and E-selectin were induced by TNF-α in HUVECs at both the mRNA and protein levels. The mRNA and protein expressions of VCAM-1 and ICAM-1, but not E-selectin, were both significantly suppressed by Tanshinone IIA in a dose dependent manner. In addition, the TNF-α-induced mRNA expression of fractalkine/CX3CL1 and the level of soluble fractalkine were both reduced by Tanshinone IIA. We also found that Tanshinone IIA significantly inhibited TNF-α-induced nuclear translocation of NF-κB which was resulted from the inhibitory effect of Tanshinone IIA on the TNF-α-activated phosphorylation of IKKα, IKKβ, IκB and NF-κB. As one of the major components of Salvia miltiorrhiza, Tanshinone IIA alone exerted more potent effect on inhibiting the adhesion of monocytes to vascular endothelial cells when compared with Salvia miltiorrhiza. All together, these results demonstrate a novel underlying mechanism for the anti-inflammatory effect of Tanshinone IIA by modulating TNF-α-induced expression of VCAM-1, ICAM-1 and fractalkine through inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway in human vascular endothelial cells.
authors.affiliation: Department of Chinese Medicine and Mitochondrial Research Unit, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Chinese Medicine and Mitochondrial Research Unit, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Chen-Fu
authors.initials: CF
authors.lastname: Chu
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.
authors.forename: Chao-Nin
authors.initials: CN
authors.lastname: Wang
authors.affiliation: Department of Chinese Medicine and Mitochondrial Research Unit, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Hsiao-Ting
authors.initials: HT
authors.lastname: Wu
authors.affiliation: Department of Chinese Medicine and Mitochondrial Research Unit, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Bi
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC. Electronic address: jonghwei@mail.cgu.edu.tw.
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
authors.affiliation: Department of Chinese Medicine and Mitochondrial Research Unit, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC. Electronic address: shenteng@adm.cgmh.org.tw.
authors.forename: Sheng-Teng
authors.initials: ST
authors.lastname: Huang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism* / Q000517:prevention & control; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D012333:RNA, Messenger / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000893:Anti-Inflammatory Agents; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D004365:Drugs, Chinese Herbal; D019040:E-Selectin; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C021751:tanshinone; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C028972:dan-shen root extract
keywords: Fractalkine; ICAM-1; IKK/NF-κB; TNF-α; Tanshinone IIA; VCAM-1