Mechanistic studies on the anti-DOX cardiotoxicity of polysaccharides of Brassica rapa L. based on the regulation of Nrf2/HO-1 signaling pathway
10.16438/j.0513-4870.2023-1065
- VernacularTitle:基于Nrf2/HO-1信号通路调控的恰玛古多糖抗多柔比星心肌毒性的机制研究
- Author:
Jun-ting GUO
1
;
Ting-ting ZHAO
1
;
Talpbek YESEM
1
;
Rui-juan GAO
2
;
Gui-hua LIU
3
Author Information
1. Xinjiang Institute of Materia Medica, Urumqi 830000, China; Xinjiang Key Laboratory of Uygur Medical Research, Urumqi 830000, China
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
3. Xinjiang Institute of Materia Medica, Urumqi 830000, China; Xinjiang Key Laboratory of Uygur Medical Research, Urumqi 830000, China; College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
- Publication Type:Research Article
- Keywords:
polysaccharides of Brassica rapa L.;
oxorubicin;
myocardial toxicity;
oxidative stress;
Nrf2/HO-1 signaling pathway
- From:
Acta Pharmaceutica Sinica
2024;59(4):930-938
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the role of chamagogic polysaccharides (polysaccharides of Brassica rapa L., BRPs) against doxorubicin (DOX) cardiotoxicity and related mechanisms, H9c2 cells were selected for the study, and the effects of BRPs on DOX induced damage in H9c2 cells were detected by cell counting kit-8 (CCK-8); H9c2 cells were divided into the control group, the model group, and the drug group (0.5-3 mg·mL-1); the control group was cultured under normal conditions, and the remaining groups were induced for 24 h by 1 μmol·L-1 DOX after treatment. Apoptosis was detected by flow cytometry; the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in each group; intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected. Western blot was used to detect the expression of proteins related to the apoptosis and transcription factor NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Compared with the control group, DOX-induced H9c2 cell injury was characterized by decreased cell viability, increased apoptosis, elevated LDH and MDA levels, decreased SOD activity, significantly increased ROS levels, and significantly decreased MMP; the level of B cell lymphoma-2 (Bcl-2) protein decreased, and the level of Bcl-2 associated X protein (Bax) increased significantly; In the model group, the expression levels of Nrf-2, HO-1, quinone oxidoreductase 1 (NQO1) were reduced, and the expression levels of Kelch-like ECH-associated protein 1 (Keap1) and phosphorylated p38 mitogen-activated protein kinase were significantly increased, Moreover, BRPs (0.5-3 mg·mL-1) increased the protein expression levels of Nrf2, HO-1, and NQO1, and decreased the levels of Keap1 and phosphorylated p38 mitogen-activated protein kinase. In summary, the ability of BRPs to protect H9c2 cells and inhibit apoptosis may be related to their regulation of the Nrf2/HO-1 pathway to antagonize oxidative stress.
