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Kuanxiong aerosol inhibits apoptosis and attenuates isoproterenol-induced myocardial injury through the mitogen-activated protein kinase pathway.
- Source :
-
Journal of ethnopharmacology [J Ethnopharmacol] 2021 Apr 06; Vol. 269, pp. 113757. Date of Electronic Publication: 2020 Dec 25. - Publication Year :
- 2021
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Abstract
- Ethnopharmacological Relevance: Kuanxiong aerosol (KXA) is a common clinical drug based on Fangxiang Wentong (FXWT) therapy in the treatment of angina pectoris. However, the pharmacological mechanism of KXA in the prevention and treatment of myocardial injury (MI) is not clear.<br />Aim of the Study: The purpose of this study was to explore the protective effect of KXA on isoproterenol (ISO)-induced MI in rats.<br />Materials and Methods: The study included male Wistar Kyoto rats (age: 6 weeks). The rats were randomly divided into the following 5 groups (n = 6 per group): control group, ISO group, isosorbide mononitrate (ISMN) group (5 mg/kg), KXA-L group (0.1 mL/kg), and KXA-H group (0.3 mL/kg). The rats in the last three groups were given intragastric administration for 14 days, and rats in control group and ISO group were given the same amount of normal saline daily. ISO (120 mg/kg) was used to induce MI on the 13th and 14th days. We assessed electrocardiograms (ECGs), myocardial specific enzymes, histopathological changes, and apoptosis.<br />Results: We found that KXA reduced the increase in the ST-segment amplitude (elevation or depression) and the levels of myocardial marker enzymes induced by ISO in MI rats, improved the pathological changes in myocardial tissue, and reduced cardiomyocyte apoptosis. At the same time, KXA significantly inhibited the up-regulation of caspase-3 and Bax expression and down-regulation of Bcl-2 expression induced by ISO. RNA sequencing showed that 90 up-regulated genes induced by ISO were down-regulated after KXA treatment, whereas 27 down-regulated genes induced by ISO were up-regulated after KXA treatment. In addition, KEGG pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathway may be an important target of KXA in the treatment of ISO-induced MI in rats. The results of RNA sequencing verified by Western blot analysis showed that KXA significantly inhibited the activation of the ISO-induced MAPK pathway.<br />Conclusions: KXA improves cardiac function in MI rats by inhibiting apoptosis mediated by the MAPK signaling pathway.<br /> (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Aerosols chemistry
Aerosols therapeutic use
Animals
Cardiotonic Agents chemistry
Cardiotonic Agents therapeutic use
Caspase 3 genetics
Down-Regulation drug effects
Drugs, Chinese Herbal chemistry
Drugs, Chinese Herbal therapeutic use
Electrocardiography drug effects
Gene Expression Regulation drug effects
Isoproterenol toxicity
Male
Myocardial Infarction chemically induced
Myocardium metabolism
Myocardium pathology
Proto-Oncogene Proteins c-bcl-2 genetics
Rats, Inbred WKY
Transcriptome drug effects
Up-Regulation drug effects
bcl-2-Associated X Protein genetics
Rats
Aerosols pharmacology
Apoptosis drug effects
Cardiotonic Agents pharmacology
Drugs, Chinese Herbal pharmacology
MAP Kinase Signaling System drug effects
Myocardial Infarction drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 269
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33359915
- Full Text :
- https://doi.org/10.1016/j.jep.2020.113757