title: Liguzinediol protects against cardiac fibrosis in rats in vivo and in vitro.
abstract: Cardiac fibrosis plays a causal role in the development of heart failure, and anti-fibrotic therapy represents a promising strategy to mitigate heart failure. The purpose of this study was to investigate the effect of a new drug-liguzinediol on cardiac fibrosis of heart failure Male Sprague-Dawley rats (SD) rats and the underlying mechanisms. Liguzinediol was administered to rats that were injected with doxorubicin (Dox) for four weeks. Two weeks later, its effects on cardiac fibrosis were assessed by haematoxylin and eosin (HE) staining and Masson staining. The collagen content was determined by Elisa, and protein expression was detected by western blot in vitro and in vivo. Liguzinediol decreased cardiac muscle fiber break evidenced by HE staining and it significantly reduced cardiac fibrosis evidenced by Masson staining in DOX-treated rats. In addition, the hydroxyproline level and the ratio of type I/III collagens were also significantly decreased, and western blot assays showed that liguzinediol regulated the balance between matrix matalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) to protect cardiac remodeling in vivo and in vitro. These data collectively indicated that liguzinediol could protect against cardiac fibrosis in rats. Liguzinediol could be exploited to be a promising candidate for cardiac fibrosis.
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Qi
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Qiuyi
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China; Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, China. Electronic address: qxliyu@sina.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. Electronic address: hmbian@sina.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Bian
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C572935:2,5-dihydroxymethyl-3,6-dimethylpyrazine; D002316:Cardiotonic Agents; D024042:Collagen Type I; D024061:Collagen Type III; D011719:Pyrazines; D019715:Tissue Inhibitor of Metalloproteinase-1; D004317:Doxorubicin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline
keywords: Cardiac fibroblasts; Cardiac fibrosis; Doxorubicin; Liguzinediol; MMP; TIMP