Jujuboside A attenuates norepinephrine-induced apoptosis of H9c2 cardiomyocytes by modulating MAPK and AKT signaling pathways

Wan,Chang‑Rong; Han,Dan‑Dan; Xu,Jian‑Qin; Yin,Peng; Xu,Xiao‑Long; Mei,Chen; Liu,Feng‑Hua; Xia,Zhao‑Fei

doi:10.3892/mmr.2017.7938

Jujuboside A attenuates norepinephrine-induced apoptosis of H9c2 cardiomyocytes by modulating MAPK and AKT signaling pathways

Authors:
- Chang‑Rong Wan
- Dan‑Dan Han
- Jian‑Qin Xu
- Peng Yin
- Xiao‑Long Xu
- Chen Mei
- Feng‑Hua Liu
- Zhao‑Fei Xia
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Affiliations: CAU‑BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China, Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Disease, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, P.R. China, Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, P.R. China
Published online on: November 2, 2017 https://doi.org/10.3892/mmr.2017.7938
Pages: 1132-1140

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Abstract

Cardiomyocyte apoptosis is closely associated with the pathogenesis of heart failure. Jujuboside A (JUA) is a type of saponin isolated from the seeds of Zizyphus jujuba. In traditional Chinese medicine, it is believed that JUA possesses multiple biological effects, including antianxiety, antioxidant and anti‑inflammatory activities. The present study aimed to evaluate the effects of JUA on norepinephrine (NE)‑induced apoptosis of H9c2 cells and to investigate its underlying mechanisms. Rat H9c2 cardiomyocytes were pretreated with JUA and were then exposed to NE as an in vitro model of myocardial apoptosis. A cell viability assay, scanning electron microscopy, transmission electron microscopy, flow cytometry assay, acridine orange/ethidium bromide staining, reverse transcription‑quantitative polymerase chain reaction and western blotting, all revealed that NE induced H9c2 cell apoptosis. The results demonstrated that NE inhibited cell viability, and enhanced cell damage and apoptosis of H9c2 cells. Conversely, pretreatment with JUA was able to reverse NE‑induced decreased cell viability and increased apoptosis. Furthermore, JUA suppressed upregulation of the B‑cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio, and inhibited the increased protein expression levels of cleaved caspase‑3 and cleaved caspase‑9 following NE exposure. However, the protein expression levels of cleaved caspase‑12 and cleaved caspase‑8 were not significantly altered following exposure to NE or JUA pretreatment. In addition, in JUA‑pretreated cells, the protein expression levels of phosphorylated (p)‑p38 and p‑c‑Jun N‑terminal kinase were downregulated compared with in NE‑treated cells. Furthermore, JUA regulated the activation of extracellular signal‑regulated kinase (ERK) in NE‑treated cells and significantly increased the expression levels of p‑AKT. Taken together, these data suggested that JUA may protect against NE‑induced apoptosis of cardiomyocytes via modulation of the mitogen‑activated protein kinase and AKT signaling pathways. Therefore, JUA may be considered a potential therapeutic strategy for the treatment of heart disease.

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