title: Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling.
abstract: The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre-treatment of DSS significantly improved cell survival and protected against I/R-induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy- and apoptosis-related proteins (including p62, LC3-II, Beclin-1, Bax, and Caspase-3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre-treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation.
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Guanwei
authors.initials: G
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Patrick Fordjour
authors.initials: PF
authors.lastname: Asare
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Boli
authors.initials: B
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. yanzhu.harvard@icloud.com.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China. yanzhu.harvard@icloud.com.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China. yanzhu.harvard@icloud.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. gaoxiumei@tjutcm.edu.cn.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China. gaoxiumei@tjutcm.edu.cn.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China. gaoxiumei@tjutcm.edu.cn.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D007773:Lactates; C035055:3,4-dihydroxyphenyllactic acid; D007770:L-Lactate Dehydrogenase; D058570:TOR Serine-Threonine Kinases; D003402:Creatine Kinase
keywords: Danshensu; I/R injury; apoptosis; autophagy; mTOR