Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Wang,Wei; Liu,Da; Yang,Liyun; Chen,Lixia; Miao,Mengdan; Liu,Yongsheng; Yin,Yajuan; Wei,Mei; Liu,Gang; An,Yonghui; Zheng,Mingqi

doi:10.3892/ijmm.2023.5226

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Authors:
- Wei Wang
- Da Liu
- Liyun Yang
- Lixia Chen
- Mengdan Miao
- Yongsheng Liu
- Yajuan Yin
- Mei Wei
- Gang Liu
- Yonghui An
- Mingqi Zheng
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Affiliations: Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China, Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China
Published online on: January 30, 2023 https://doi.org/10.3892/ijmm.2023.5226
Article Number: 23
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate‑buffered saline (PBS; 200 µl) were subcutaneously implanted into 6‑week‑old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N‑terminal (NT)‑pro hormone B‑type natriuretic peptide, were assessed using enzyme‑linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis‑related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit‑8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis‑related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II‑mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.

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