title: Shensong Yangxin Capsule prevents diabetic myocardial fibrosis by inhibiting TGF-β1/Smad signaling.
abstract: BACKGROUND
  Shensong Yangxin Capsule (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the effect of SSYX on interstitial fibrosis in diabetic cardiomyopathy is unknown. The objective of this study was to investigate the effects of SSYX on myocardial fibrosis in diabetic rats.
  
  
  METHODS
  The antifibrotic effect of SSYX was investigated in streptozocin (STZ)-induced diabetic rats with high fat-diet (HFD). Fasting blood glucose, heart weight/body weight (HW/BW) ratio, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured. Echocardiography and histology examination were carried out to evaluate heart function. Expressions of Smad7, TGF-β1, collagen I (col-1), collagen III (col-3), MMP-2, MMP-9 and α-SMA mRNA in heart tissues were measured by real time polymerase chain reaction (PCR). TGF-β1, Smad2/3, p-Smad2/3 and Smad7 protein levels were measured by western blot analysis. Proliferation of cardiac fibroblast was detected via immunofluorescence.
  
  
  RESULTS
  SSYX markedly decreased HW/BW ratio and improved the impaired cardiac function of type-2 diabetes mellitus (T2DM) rats. Transmission electron microscopy (TEM), haematoxylin and eosin (HE) and Masson staining results showed that SSYX attenuated cardiac fibrosis and collagen deposition in T2DM rats. Moreover, mRNA levels of TGF-β1, col-1, col-3, MMP-2, MMP-9 and α-SMA were downregulated, whereas Smad7 expression was upregulated after treatment with SSYX in rats with cardiac fibrosis. Furthermore, SSYX decreased protein levels of TGF-β1 and p-Smad2/3, and increased Smad7 expression.
  
  
  CONCLUSIONS
  TGF-β1/Smad signaling is involved in the cardiac fibrosis in diabetic cardiomyopathy and SSYX inhibits fibrosis and improves cardiac function via suppressing this pathway. Therefore, SSYX might be considered as an alternative therapeutic remedy for diabetic cardiomyopathy.
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Muhammad U
authors.initials: MU
authors.lastname: Bilal
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Du
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang 050035, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: nd6688@163.com.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China; Institute of Cardiovascular Research, Harbin Medical University, Harbin 150081, China. Electronic address: hmuzhangyong@hotmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005355:Fibrosis; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000187:drug effects / Q000378:metabolism; D051900:Smad3 Protein / Q000187:drug effects / Q000378:metabolism; D051906:Smad7 Protein / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D051899:Smad2 Protein; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; C530959:shensongyangxin
keywords: Avicularin (Pubchem CID: 5490064); Berberine hydrochloride (Pubchem CID: 12456); Cardiac fibrosis; Columbamine (Pubchem CID: 72310); Demethyleneberberine (Pubchem CID: 363209); Diabetic cardiomyopathy; Ginsenoside Rb1 (Pubchem CID: 9898279 ); Linarin (Pubchem CID: 5317025); Nardosinone (Pubchem CID: 168136); Oleanic acid (Pubchem CID: 10494); Paeoniflorin (Pubchem CID: 442534); Quercetin (Pubchem CID: 5280343); Salvianolic acid B (Pubchem CID: 71433917 ); Salvianolic acid E (Pubchem CID: 49770697); Saponin (Pubchem CID: 11007422); Schisantherin A (Pubchem CID: 151529); Schizandrin B (Pubchem CID: 108130); Shensong Yangxin Capsule; Smad; Sodium danshensu (Pubchem CID: 23711819); Spinosin (Pubchem CID: 155692); TGF-β1; Tanshinone I (Pubchem CID: 114917)