Isovaleroylbinankadsurin A ameliorates cardiac ischemia/reperfusion injury through activating GR dependent RISK signaling.

Autor: Zuo YH; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China., Liu YB; TCM and Ethnomedicine Innovation & Development Laboratory, Sino-Pakistan TCM and Ethnomedicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China., Cheng CS; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China., Yang YP; TCM and Ethnomedicine Innovation & Development Laboratory, Sino-Pakistan TCM and Ethnomedicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China., Xie Y; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China., Luo P; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China., Wang W; TCM and Ethnomedicine Innovation & Development Laboratory, Sino-Pakistan TCM and Ethnomedicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China. Electronic address: wangwei402@hotmail.com., Zhou H; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Taipa, Macao, PR China. Electronic address: hzhou@must.edu.mo.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2020 Aug; Vol. 158, pp. 104897. Date of Electronic Publication: 2020 May 16.
DOI: 10.1016/j.phrs.2020.104897
Abstrakt: Ischemia/reperfusion (I/R) injury is a pathological process caused by reperfusion. The prevention of I/R injury is of great importance as it would enhance the efficacy of myocardial infarction treatment in patients. Isovaleroylbinankadsurin A (ISBA) has been demonstrated to possess multiple bioactivities for treating diseases. However, its protective effect on myocardial I/R injury remains unknown. In this study, the cardiomyocytes hypoxia/reoxygenation (H/R) in vitro model and coronary artery ligation in vivo model were used to examine the protective effect of ISBA. Apoptosis was determined by flow cytometry and Caspase 3 activity. Protein level was determined by Western blot. The mitochondrial viability was examined with mitochondrial viability stain assay. Mitochondrial membrane potential was detected by JC-1 staining and reactive oxygen species (ROS) was stained with 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). The binding interactions between ISBA and receptors was simulated by molecular docking. Results showed that ISBA effectively protected cardiomyocytes from I/R injury in in vitro and in vivo models. It remarkably blocked the apoptosis induced by H/R injury through the mitochondrial dependent pathway. Activation of the reperfusion injury salvage kinase (RISK) pathway was demonstrated to be essential for ISBA to exert its protective effect on cardiomyocytes. Moreover, molecular docking indicated that ISBA could directly bind to glucocorticoid receptor (GR) and thus induce its activation. Furthermore, the treatment of GR inhibitor RU486 partially counteracted the protective effect of ISBA on cardiomyocytes, consistent with the results of docking.Most attractively, by activating GR dependent RISK pathway, ISBA significantly elevated the cellular anti-oxidative capacity and hence alleviated oxidative damage induced by I/R injury. In conclusion, our study proved that ISBA protected the heart from myocardial I/R injury through activating GR dependent RISK pathway and consequently inhibiting the ROS generation. It provides a valuable reference for ISBA to be developed as a candidate drug for cardiovascular diseases.
Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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