Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts
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-<i>p</i>-coumaroyl-4-aminobutan-1-ol (alk-A), an organic amide alkaloid and hippophamide (...
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doaj-4effb8e2dd1f4c588055872dfd0595db2021-03-30T23:05:17ZengMDPI AGMolecules1420-30492021-03-01261946194610.3390/molecules26071946Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 CardiomyoblastsWenNa Zhou0Jian Ouyang1Na Hu2Gang Li3Hong-Lun Wang4Department of Life Sciences and Health, QiuZhen College, Huzhou University, Huzhou 313000, ChinaCAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, ChinaCAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, ChinaCenter for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, ChinaCAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, ChinaBackground: 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-<i>p</i>-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.https://www.mdpi.com/1420-3049/26/7/1946alkaloiddoxorubicinapoptosismitochondrial functionseabuckthorn |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
WenNa Zhou Jian Ouyang Na Hu Gang Li Hong-Lun Wang |
spellingShingle |
WenNa Zhou Jian Ouyang Na Hu Gang Li Hong-Lun Wang Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts Molecules alkaloid doxorubicin apoptosis mitochondrial function seabuckthorn |
author_facet |
WenNa Zhou Jian Ouyang Na Hu Gang Li Hong-Lun Wang |
author_sort |
WenNa Zhou |
title |
Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts |
title_short |
Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts |
title_full |
Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts |
title_fullStr |
Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts |
title_full_unstemmed |
Protective Effect of Two Alkaloids from <i>Hippophae rhamnoides </i>Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts |
title_sort |
protective effect of two alkaloids from <i>hippophae rhamnoides </i>linn. against doxorubicin-induced toxicity in h9c2 cardiomyoblasts |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-03-01 |
description |
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-<i>p</i>-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. |
topic |
alkaloid doxorubicin apoptosis mitochondrial function seabuckthorn |
url |
https://www.mdpi.com/1420-3049/26/7/1946 |
work_keys_str_mv |
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