Emodin protects against homocysteine-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways
Copyright © 2022 Elsevier B.V. All rights reserved..
Elevated levels of plasma homocysteine (Hcy) causes severe cardiac dysfunction, which is closely associated with oxidative stress. Emodin, a naturally occurring anthraquinone derivative, has been shown to exert antioxidant and anti-apoptosis activities. However, whether emodin could protect against Hcy-induced cardiac dysfunction remains unknown. The current study aimed to investigate the effects of emodin on the Hcy-induced cardiac dysfunction and its molecular mechanisms. Rats were fed a methionine diet to establish the animal model of hyperhomocysteinemia (HHcy). H9C2 cells were incubated with Hcy to induce a cell model of Hcy-injured cardiomyocytes. ELISA, HE staining, carotid artery and left ventricular cannulation, MTT, fluorescence staining, flow cytometry and western blotting were used in this study. Emodin significantly alleviated the structural damage of the myocardium and cardiac dysfunction from HHcy rats. Emodin prevented apoptosis and the collapse of MMP in the Hcy-treated H9C2 cells in vitro. Further, emodin reversed the Hcy-induced apoptosis-related biochemical changes including decreased Bcl-2/Bax protein ratio, and increased protein expression of Caspase-9/3. Moreover, emodin suppressed oxidative stress in Hcy-treated H9C2 cells. Mechanistically, emodin significantly inhibited the Hcy-activated MAPK by reducing ROS generation in H9C2 cells. Furthermore, emodin upregulated NO production by promoting the protein phosphorylation of Akt and eNOS in injured cells. The present study shows that emodin protects against Hcy-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:940 |
|---|---|
| Enthalten in: |
European journal of pharmacology - 940(2023) vom: 05. Feb., Seite 175452 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Ya-Ping [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
0LVT1QZ0BA |
|---|
| Anmerkungen: |
Date Completed 17.01.2023 Date Revised 17.01.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ejphar.2022.175452 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM350411123 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM350411123 | ||
| 003 | DE-627 | ||
| 005 | 20231226044928.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejphar.2022.175452 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1167.xml |
| 035 | |a (DE-627)NLM350411123 | ||
| 035 | |a (NLM)36529277 | ||
| 035 | |a (PII)S0014-2999(22)00713-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Ya-Ping |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Emodin protects against homocysteine-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.01.2023 | ||
| 500 | |a Date Revised 17.01.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a Elevated levels of plasma homocysteine (Hcy) causes severe cardiac dysfunction, which is closely associated with oxidative stress. Emodin, a naturally occurring anthraquinone derivative, has been shown to exert antioxidant and anti-apoptosis activities. However, whether emodin could protect against Hcy-induced cardiac dysfunction remains unknown. The current study aimed to investigate the effects of emodin on the Hcy-induced cardiac dysfunction and its molecular mechanisms. Rats were fed a methionine diet to establish the animal model of hyperhomocysteinemia (HHcy). H9C2 cells were incubated with Hcy to induce a cell model of Hcy-injured cardiomyocytes. ELISA, HE staining, carotid artery and left ventricular cannulation, MTT, fluorescence staining, flow cytometry and western blotting were used in this study. Emodin significantly alleviated the structural damage of the myocardium and cardiac dysfunction from HHcy rats. Emodin prevented apoptosis and the collapse of MMP in the Hcy-treated H9C2 cells in vitro. Further, emodin reversed the Hcy-induced apoptosis-related biochemical changes including decreased Bcl-2/Bax protein ratio, and increased protein expression of Caspase-9/3. Moreover, emodin suppressed oxidative stress in Hcy-treated H9C2 cells. Mechanistically, emodin significantly inhibited the Hcy-activated MAPK by reducing ROS generation in H9C2 cells. Furthermore, emodin upregulated NO production by promoting the protein phosphorylation of Akt and eNOS in injured cells. The present study shows that emodin protects against Hcy-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cardiac dysfunction | |
| 650 | 4 | |a Emodin | |
| 650 | 4 | |a Homocysteine | |
| 650 | 4 | |a MAPK | |
| 650 | 4 | |a Nitric oxide | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Emodin |2 NLM | |
| 650 | 7 | |a KA46RNI6HN |2 NLM | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Homocysteine |2 NLM | |
| 650 | 7 | |a 0LVT1QZ0BA |2 NLM | |
| 700 | 1 | |a Zhou, Guang Hai |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yu-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qi-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Kyung Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Song Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Jin Fu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of pharmacology |d 1967 |g 940(2023) vom: 05. Feb., Seite 175452 |w (DE-627)NLM000029769 |x 1879-0712 |7 nnns |
| 773 | 1 | 8 | |g volume:940 |g year:2023 |g day:05 |g month:02 |g pages:175452 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejphar.2022.175452 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 940 |j 2023 |b 05 |c 02 |h 175452 | ||