Total flavonoids from Anchusa italica improves cardiac function and attenuates cardiac remodeling post-myocardial infarction in mice  

作　　者：WANG Shou-bao SONG Jun-ke WANG Rong-rong GAO Li ZHANG Li FANG Lian-hua LYU Yang DU Guan-hua 

机构地区：[1]Beijing Key Laboratory of Drug Targets Identification and Drug Screening,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [2]Beijing Key Laboratory of Polymorphic Drugs,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [3]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [4]China Key Laboratory of Traditional Uygur Medical Prescription,Xinjiang Uygur Autonomous Region Institute of Traditional Uygur Medicine,Urumqi 830001,China

出　　处：《中国药理学与毒理学杂志》2019年第9期698-699,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：CAMS Innovation Fund for Medical Sciences(CIFMS)318(2016-I2M-3-007);National Natural Science Foundation of China(81673422;and 81202538)

摘　　要：OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effecOBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China. Our previous study showed that total flavonoids from Anchusa italica（TFAI） exhibited potent cardioprotection on acute ischemia/reperfusion injured rats. This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism. METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis. The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice. After surgery, the mice were orally fed with TFAI at the doses of 10, 30 and 50 mg·kg-1 body mass per day for a total of four weeks. Cardiac function and infarct size were measured, and the levels of inflammatory mediators were detected. Hematoxylin and eosin（HE） stain and Masson Trichrome stain were performed. The apoptotic factors such as Bax, Bcl-2 and cleaved caspase3 as well as the key proteins in the PI3 K/Akt/m TOR signaling pathway were examined by Western blotting. RESULTS The content of total flavonoids in TFAI was 56.2%. Four weeks following the MI surgery, TFAI enhanced the survival rate in post-MI mice. TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS. Assay of inflammation factors showed that the sera levels of TNF-α, IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group. HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume. Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were significantly downregulated following TFAI treatment. Additionally, TFAI treatment significantly suppressed the activation of the PI3 K/Akt/m TOR signaling pathway. CONCLUSI

关 键 词：total flavonoids Anchusa italica cardiac function 

分 类 号：R73[医药卫生—肿瘤]