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Protective Effect of Two Alkaloids from Hippophae rhamnoides Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts
- Source :
- Molecules, Volume 26, Issue 7, Molecules, Vol 26, Iss 1946, p 1946 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- Background: Doxorubicin (Dox) is one of the most frequently prescribed anti-cancer drugs. However, clinical application with Dox is limited due to its potentially fatal cumulative cardiotoxicity. N-p-coumaroyl-4-aminobutan-1-ol (alk-A), an organic amide alkaloid and hippophamide (alk-B), a rare pyridoindole alkaloid were successfully obtained by purification and separation of seabuckthorn seed residue in our previous research. This study was undertaken to investigate the protective effect of alk-A and alk-B against Dox-induced embryonic rat cardiac cells (H9c2 cells) apoptosis. Methods: H9c2 cells were treated with Dox (2.5 µM) in the presence of alk-A and alk-B (10, 20, and 40 µM) and incubated for 24 h. Results: It was shown that pretreatment of the H9c2 cells with alk-A and alk-B significantly reduced Dox-induced apoptosis. Alk-A and alk-B both inhibited reactive oxygen species (ROS) production and suppressed cleaved-caspase-3 protein expression and the activation of JNK (Jun N-terminal kinases), as well as increasing ATP levels, favoring mitochondrial mitofusin protein expression, and relieving damage to mitochondrial DNA. Conclusions: These results suggest that alk-A and alk-B can inhibit Dox-induced apoptosis in H9C2 cardiac muscle cells via inhibition of cell apoptosis and improvement of mitochondrial function, while alk-B showed more protection. Alk-B could be a potential candidate agent for protecting against cardiotoxicity in Dox-exposed patients.
- Subjects :
- Cell Survival
Pharmaceutical Science
Pharmacology
seabuckthorn
doxorubicin
Article
Antioxidants
Analytical Chemistry
Cell Line
lcsh:QD241-441
Mitochondrial Proteins
03 medical and health sciences
0302 clinical medicine
Alkaloids
lcsh:Organic chemistry
mitochondrial function
hemic and lymphatic diseases
Drug Discovery
Hippophae
medicine
Animals
Doxorubicin
Myocytes, Cardiac
Physical and Theoretical Chemistry
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Reactive oxygen species
Cardiotoxicity
Chemistry
Kinase
Alkaloid
Organic Chemistry
Cardiac muscle
apoptosis
alkaloid
Mitochondria
Rats
Oxidative Stress
medicine.anatomical_structure
Chemistry (miscellaneous)
Apoptosis
030220 oncology & carcinogenesis
Toxicity
Molecular Medicine
Reactive Oxygen Species
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....024181499a09ee23f602ca44015e55f9