Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats.
Oxidative stress plays an important role in the initiation and development of myocardial injury (MI). The peroxisome proliferator-activated receptor gamma coactivator-1α (PGC‑1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is considered to be a potential target for cardioprotection in MI. Acetyl-11-keto-β-boswellic acid (AKBA) is the major organic acid component extracted from Boswellia serrata Roxb. ex Colebr. Hydroxysafﬂor yellow A (HSYA) is the principal active constituent of Carthamus tinctorius L. In the present study, we aimed to investigate the cardioprotective effects of HSYA and AKBA in combination in vivo and in vitro, as well as the underlying mechanisms responsible for these effects. For this purpose, MI was produced in Sprague-Dawley rats by subcutaneous injection with isoproterenol. To model ischemic-like conditions in vitro, H9C2 cells were subjected to oxygen-glucose deprivation (OGD). The levels of creatine kinase-MB (CK‑MB), lactate dehydrogenase (LDH), malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity were examined as well as apoptotic cell death. Mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm or MMP) were measured using MitoSOX Red and 5,5',6,6'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) dye. The expression of PGC-1α and Nrf2 was quantified by western blot analysis and immunohistochemistry. HSYA and AKBA prevented myocardial pathological changes, signiﬁcantly reduced the blood levels of CK-MB and LDH, and decreased apoptotic cell death. They significantly increased the expression of PGC-1α and Nrf2, and the activity of the antioxidant enzyme SOD and also decreased the levels of MDA and ROS. Moreover, the reduction in MMP was partly prevented by HSYA and AKBA. Taken together, these findings elucidate the underlying mechanisms through which HSYA and AKBA protect against MI. Additionally, HSYA and AKBA appear to act synergistically in order to exert cardioprotective effects.
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Minchun
M
Chen
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mingming
M
Wang
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Qiong
Q
Yang
Department of Pharmacology, College of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Min
M
Wang
Department of Pharmacology, College of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Zhipeng
Z
Wang
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Yanrong
Y
Zhu
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Yikai
Y
Zhang
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Chao
C
Wang
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Yanyan
Y
Jia
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Yuwen
Y
Li
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Aidong
A
Wen
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D052279:Creatine Kinase, MB Form / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004357:Drug Synergism; D005786:Gene Expression Regulation; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D006335:Heart Injuries / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000494:pharmacology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
D000975:Antioxidants; D002316:Cardiotonic Agents; D004338:Drug Combinations; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D011809:Quinones; D017382:Reactive Oxygen Species; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; C085278:hydroxysafflor yellow A; D002599:Chalcone; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D052279:Creatine Kinase, MB Form; D005947:Glucose; D007545:Isoproterenol; D010100:Oxygen