The effect of astragaloside IV on a model of isoproterenol-induced hypertrophic injury in H9c2 cells

Yang Long; Yuan Xiao; Chun Chen; Chao Peng; Yuxi Zhang

doi:10.2478/acph-2026-0006

Abstract

The objective of this study was to explore the protective effect of astragaloside IV on a model of isoproterenol-induced (ISO) hyper-trophic injury in rat cardiomyocytes H9c2 (cell line derived from embryonic BD1X rat heart tissue). A cell hypertrophy injury model was established (H9c2 cells treated with 100 μmol L–1 ISO). The cells were divided into normal control, a model group, and an astragalo-side IV group at several concentrations. Astragaloside IV was pre-administered for 2 hours, followed by ISO treatment for 24 hours. Cell viability, cell surface area, apoptosis rate, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS), superoxide dismutase (SOD), the mRNA levels of Bcl-2, Bax, p62, and LC3, the protein expressions of Sirt1, p62, caspase-3, beclin, and p53 and the LC3II/LC3I ratio were detected. Astragaloside IV significantly alleviated ISO-induced hypertrophy injury in H9c2 cells, reduced cell surface area and LDH release, decreased apoptosis rate and intracellular ROS levels, increased SOD levels, upregulated the expressions of autophagy-related mRNA and proteins, and downregulated the expressions of apoptosis-related mRNA and proteins. Astragaloside IV can effectively inhibit ISO-induced hypertrophy and apoptosis in H9c2 cells, and its mechanism may be related to promoting auto-phagy and reducing oxidative stress.

References

F. Bazgir, J. Nau, S. Nakhaei-Rad, E. Amin, M. J. Wolf, J. J. Saucerman, K. Lorenz and M. R. Ahmadian, The microenvironment of the pathogenesis of cardiac hypertrophy, Cells 12 (2023) Article ID 1780 (35 pages); https://doi.org/10.3390/cells12131780
Search in Google Scholar Back to article
Y. Bei, Y. Zhu, M. Wei, M. Yin, L. Li, C. Chen, Z. Huang, X. Liang, J. Gao, J. Yao, P. H. van der Kraak, A. Vink, Z. Lei, Y. Dai, H. Chen, Y. Liang, J. PG Sluijter and J. Xiao, HIPK1 inhibition protects against pathological cardiac hypertrophy by inhibiting the CREB-C/EBPβ axis, Adv. Sci. 10(18) (2023) e2300585 (15 pages); https://doi.org/10.1002/advs.202300585
Search in Google Scholar Back to article
G. Chen, N. An, J. Shen, H. Chen, Y. Chen, J. Sun, Z. Hu, J. Qiu, C. Jin, S. He, L. Mei, Y. Sui, W. Li, P. Chen, X. Guan, M. Chu, Y. Wang, L. Jin, K. Kim, X. Li, W. Cong and X. Wang, Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice, Nat. Commun. 14 (2023) Article ID 1235 (18 pages); https://doi.org/10.1038/s41467-023-36895-1
Search in Google Scholar Back to article
L. Zhou, M. Li, Z. Chai, J. Zhang, K. Cao, L. Deng, Y. Liu, C. Jiao, G.-M. Zou, J. Wu and F. Han, Anticancer effects and mechanisms of astragaloside IV, Oncol. Rep. 49 (2023) Article ID 5 (15 pages); https://doi.org/10.3892/or.2022.8442
Search in Google Scholar Back to article
E. M. Boorsma, J. M. ter Maaten, K. Damman, W. Dinh, F. Gustafsson, S. Goldsmith, D. Burkhoff, F. Zannad, J. E. Udelson and A. A. Voors, Congestion in heart failure: A contemporary look at physiology, diagnosis and treatment, Nat. Rev. Cardiol. 10 (2020) 641–655; https://doi.org/10.1038/s41569-020-0379-7
Search in Google Scholar Back to article
V. Castiglione, A. Aimo, G. Vergaro, L. Saccaro, C. Passino and M. Emdin, Biomarkers for the diagnosis and management of heart failure, Heart Fail. Rev. 2 (2022) 625–643; https://doi.org/10.1007/s10741-021-10105-w
Search in Google Scholar Back to article
C. Bonvicini, S. V. Faraone and C. Scassellati, Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies, Mol. Psychiatry 21 (2016) 872–884; https://doi.org/10.1038/mp.2016.74
Search in Google Scholar Back to article
M. G. Crespo-Leiro and E. Barge-Caballero, Advanced heart failure: Definition, epidemiology, and clinical course, Heart Fail. Clin. 17(4) (2021) 533–545; https://doi.org/10.1016/j.hfc.2021.06.002
Search in Google Scholar Back to article
E. La Franca, G. Manno, L. Ajello, G. Di Gesaro, C. Minà, C. Visconti, D. Bellavia, C. Falletta, G. Romano, S. Dell’ Oglio, P. Licata, A. Caronia, M. Gallo and F. Clemenza, Physiopathology and diagnosis of congestive heart failure: Consolidated certainties and new perspectives, Curr. Probl. Cardiol. 46(3) (2021) Article ID 100691 (16 pages); https://doi.org/10.1016/j.cpcardiol.2020.100691
Search in Google Scholar Back to article
Y. Gao, X. Su, T. Xue and N. Zhang, The beneficial effects of astragaloside IV on ameliorating diabetic kidney disease, Biomed. Pharmacother. 163 (2023) Article ID 114598 (12 pages); https://doi.org/10.1016/j.biopha.2023.114598
Search in Google Scholar Back to article
X. Chen, T. Yang, Y. Zhou, Z. Mei and W. Zhang; Astragaloside IV combined with ligustrazine ameliorates abnormal mitochondrial dynamics via Drp1 SUMO/deSUMOylation in cerebral ische mia-reperfusion injury, CNS Neurosci. Ther. 30(4) (2024) e14725 (18 pages); https://doi.org/10.1111/cns.14725
Search in Google Scholar Back to article
Y. Liang, B. Chen, D. Liang, X. Quan, R. Gu, Z. Meng, H. Gan, Z. Wu, Y. Sun, S. Liu and G. Dou, Pharmacological effects of astragaloside IV: A review, Molecules 28(16) (2023) Article ID 166118 (16 pages); https://doi.org/10.3390/molecules28166118
Search in Google Scholar Back to article
J. Wan, Z. Zhang, C. Wu, S. Tian, Y. Zang, G. Jin, Q. Sun, P. Wang, X. Luan, Y. Yang, X. Zhan, L. L. Ye, D. D. Duan, X. Liu and W. Zhang, Astragaloside IV derivative HHQ16 ameliorates infarction--induced hypertrophy and heart failure through degradation of lncRNA4012/9456, Sig. Transduct. Target Ther. 8 (2023) Article ID 414 (16 pages); https://doi.org/10.1038/s41392-023-01660-9
Search in Google Scholar Back to article
J. Wang, X. Pu, H. Zhuang, Z. Guo, M. Wang, H. Yang, C. Li and X. Chang, Astragaloside IV alleviates septic myocardial injury through DUSP1-prohibitin 2 mediated mitochondrial quality control and ER-autophagy, J. Adv. Res. 75 (2025) 561–580; https://doi.org/10.1016/j.jare.2024.10.030
Search in Google Scholar Back to article
P. Umapathi, O. O. Mesubi, P. S. Banerjee, N. Abrol, Q. Wang, E. D. Luczak, Y. Wu, J. M. Granger, A.-C. Wei, O. E. Reyes Gaido, L. Florea, C. Conover Talbot, G. W. Hart, N. E. Zachara and M. E. Anderson, Excessive O-GlcNAcylation causes heart failure and sudden death, Circulation 143(17) (2021) 1687–1703; https://doi.org/10.1161/CIRCULATIONAHA.120.051911
Search in Google Scholar Back to article
Z. Feng, L. Pan, C. Qiao, Y. Yang, X. Yang and Y. Xie, Cardamonin intervenes in myocardial hypertrophy progression by regulating Usp18, Phytomedicine 134 (2024) Article ID 155970 (12 pages); https://doi.org/10.1016/j.phymed.2024.155970
Search in Google Scholar Back to article
E. Dai, X. Guo, J. Wang, Q. Hu, J. Li, Q. Tang, H. Zu, H. Huan, Y. Wang, Y. Gao, G. Hu, W. Li, Z. Liu, Q. Ma, Y. Song, J. Yang, Y. Zhu, S. Huang, Z. Meng, B. Bai, Y. Chen, C. Gao, M. Huang, S. Jin, M. Lu, Z. Xu, Q. Zhang, S. Zheng, Q. Zeng and X. Qi, Investigate of the etiology and prevention status of liver cirrhosis, Zhonghua Yi Xue Za Zhi, 12 (2023) 913–919; https://doi.org/10.3760/cma.j.cn112137-20221017-02164
Search in Google Scholar Back to article
S. Kaul, A. Embaby, K. M. Heinhuis, N. S. IJzerman, A. M. Koenen, S. van der Kleij, I. Hofland, H. van Boven, J. Sanders, W. T. A. van der Graaf, R. L. Haas, A. D. R. Huitema, W. J. van Houdt and N. Steeghs, Propranolol monotherapy in angiosarcoma – A window-of-opportunity study (PropAngio), Eur. J. Cancer 202 (2024) Article ID 113974 (7 pages); https://doi.org/10.1016/j.ejca.2024.113974
Search in Google Scholar Back to article
D. E. Le, N. J. Alkayed, Z. Cao, N. N. Chattergoon, M. Garcia-Jaramillo, K. Thornburg and S. Kaul, Metabolomics of repetitive myocardial stunning in chronic multivessel coronary artery stenosis: Effect of non-selective and selective β1-receptor blockers, J. Physiol. 602(14) (2024) 3423–3448; https://doi.org/10.1113/JP285720
Search in Google Scholar Back to article
X. Wang, Y. Wang, D. Huang, S. Shi, P. Caixia, Y. Wu, S. Zherui, F. Wang, Z. Wang, Astragaloside IV regulates the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to inhibit PM2.5- mediated lung injury in mice, Int. Immunopharmacol. 112 (2022) Article ID 109186 (12 pages); https://doi.org/10.1016/j.intimp.2022.109186
Search in Google Scholar Back to article
K. Okabayashi, Y. Wakao and T. Narita, Release of secretory immunoglobulin A by submandibular gland via β adrenergic receptor stimulation, Arch. Oral Biol. 129 (2021) Article ID 105209 (5 pages); https://doi.org/10.1016/j.archoralbio.2021.105209
Search in Google Scholar Back to article
Y. Q. Tan, H. W. Chen and J. Li, Astragaloside IV: An effective drug for the treatment of cardiovascular diseases, Drug Des. Devel. Ther. 14 (2020) 3731–3746; https://doi.org/10.2147/DDDT.S272355
Search in Google Scholar Back to article
W. Tian, P. Zhang, L. Yang, P. Song, J. Zhao, H. Wang, Y. Zhao and L. Cao, Astragaloside IV alleviates doxorubicin-induced cardiotoxicity by inhibiting cardiomyocyte pyroptosis through the SIRT1/NLRP3 pathway, Am. J. Chin. Med. 52(2) (2024) 453–469; https://doi.org/10.1142/S0192415X24500198
Search in Google Scholar Back to article
Y. Su, X. Yin, X. Huang, Q. Guo, M. Ma, L. Guo, Astragaloside IV ameliorates sepsis-induced myocardial dysfunction by regulating NOX4/JNK/BAX pathway, Life Sci. 310 (2022) Article ID 121123 (10 pages); https://doi.org/10.1016/j.lfs.2022.121123
Search in Google Scholar Back to article

The effect of astragaloside IV on a model of isoproterenol-induced hypertrophic injury in H9c2 cells

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