Cryptotanshinone Inhibits STAT3 Signaling to Alleviate Cardiac Fibrosis in Type 1-like Diabetic Rats.
Cryptotanshinone is an active principal ingredient isolated from Salvia miltiorrhiza (Danshen), a medicinal plant used in China to treat cardiac disorders. The objective of this study was to investigate the effect of cryptotanshinone on myocardial fibrosis in diabetic rats. In streptozotocin-induced type 1 diabetic model hyperglycemic rats (STZ-treated rats), fasting blood glucose levels and heart weight/body weight ratio were markedly increased but both were not modified by cryptotanshinone. Additionally, cardiac performance in catheterized STZ-treated rats was improved. The histological results from Masson staining showed that cryptotanshinone attenuated cardiac fibrosis in STZ-treated rats. Moreover, both the mRNA and protein levels of the signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9, and connective tissue growth factor were reduced by cryptotanshinone in high glucose-cultured cardiomyocytes, similar to the reductions observed in the hearts of STZ-treated rats. In conclusion, while STAT3 regulates matrix metalloproteinase-9 and connective tissue growth factor expression in diabetic rats with cardiac fibrosis, cryptotanshinone inhibited fibrosis to improve cardiac function by suppressing the STAT3 pathway. Cryptotanshinone is suitable as an alternative remedy for therapy of cardiac fibrosis. Copyright © 2017 John Wiley & Sons, Ltd.
Division of Cardiology, Department of Internal Medicine, Zhongxing Branch of Taipei City Hospital, Taipei City, 10341, Taiwan.|Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 97041, Taiwan.
Shih-Hsiang
SH
Lo
Department of Pathology, E-DA Hospital, I-Shou University, Yanchao, Kaohsiung City, 82401, Taiwan.
Chao-Tien
CT
Hsu
Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 97041, Taiwan.
Ho-Shan
HS
Niu
Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 97041, Taiwan.
Chiang-Shan
CS
Niu
Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.|Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.|Institute of Medical Sciences, Chang Jung Christian University, Guiren, Tainan City, 71101, Taiwan.
Juei-Tang
http://orcid.org/0000-0002-4522-584X
JT
Cheng
Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.|Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.|Department of Pharmacy, Chia Nan University of Pharmacy & Science, Jean-Tae City, Tainan County, 71701, Taiwan.
Zhih-Cherng
ZC
Chen
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013311:Streptozocin / Q000009:adverse effects*
D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C037886:cryptotanshinone; D013311:Streptozocin
STAT3; STZ rats; cardiac fibrosis; cardiomyopathy; cryptotanshinone; type 1 diabetes