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Environ Toxicol. 2017 Mar;32(3):754-763. doi: 10.1002/tox.22275. Epub 2016 Apr 20.

Attenuation of the LPS-induced, ERK-mediated upregulation of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 by Carthamus tinctorius L in cardiomyoblasts.

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Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taiwan.
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut.
School of Medical Technology, Chung Shan Medical University, Taichung, Taiwan.
Department of Chinese Medicine, China Medical University Beigang Hospital, Taiwan.
Division of Cardiology, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan.
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
Department of Nursing, MeiHo University, Pingtung, Taiwan.
Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.


Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. LPS was previously found to dramatically upregulate expression of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 in primary cardiac fibroblasts. MMPs are capable of denaturing and degrading fibrillar collagens and other components of the extracellular matrix (ECM). Studies have shown that dysregulation of expression of MMPs is associated with development of myocardial extracellular matrix remodeling and cardiac fibrosis, which contribute to progression of heart failure. In this study, H9c2 cells and cardiac fibroblasts were divided into five treatment groups: control, LPS (1 μg/mL) and three concentrations of FCEtOH (Carthami Flos ethanolic extract) (31.25, 62.5, and 125 μg/mL). Phosphorylation of ERK-1/2 was observed to be rapidly induced upon treatment with LPS. In contrast, it was significantly suppressed by the administration of FCEtOH (125 μg/mL). Effects of FCEtOH on LPS-induced MMP-2 and MMP-9 expression in H9c2 cells occurred directly through ERK1/2 were determined. H9c2 cells were therefore pretreated with EGF-R to activate ERK pathway. Both protein levels of MMP-2 and MMP-9 and immunefluorescent signals of MMP-9 were significantly enhanced by EGFR. In contrast, MMP-2 and MMP-9 were significantly reduced after FCEtOH administration. Based on these findings, the authors concluded that FCEtOH elicits a protective effect against LPS-induced cardio-fibrosis through the ERK1/2 pathway. Carthamus tinctorius L may potentially serve as a cardio-protective agent against LPS- induced cardiac fibrosis.


: lipopolysaccharide; Carthamus tinctorius L; ERK1/2 signaling; FGF-2; MMP-2; MMP-9; cardiomyoblast fibrosis

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