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Acacetin inhibits myocardial mitochondrial dysfunction by activating PI3K/AKT in SHR rats fed with fructose

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Abstract

To explore the effect of acacetin on myocardial mitochondrial dysfunction in spontaneously hypertensive rats (SHR) with insulin resistance (IR), and the possible mechanism. Rapid IR was first induced in fructose-fed SHR, and they were then treated with acacetin (25, 50 mg/kg). After 7 weeks, the rats were tested for hypertension, IR, cardiac function, and mitochondrial damage status. Potential mechanisms of action were explored in terms of oxidative stress, mitochondrial fission and division, apoptosis, and the insulin signaling pathway. Subsequently, the PI3K gene was silenced, after intervention with acacetin (5 μM) for 24 h, and H2O2 was used to stimulate H9c2 for 4 h, it was evaluated whether silencing PI3K would affect the therapeutic effect of acacetin. In SHR fed with fructose, acacetin can improve hypertension, IR, cardiac function (LVEF, LVFS), and mitochondrial damage (mitochondria number, ATP); inhibit oxidative stress (ROS, SOD, Nrf2, Keap1), mitochondrial fission (MFF, Drp1), and myocardial cell apoptosis (apoptosis rate, Bax, Bcl-2, cytochrome c); promote mitochondrial fusion (Mfn2) and activate insulin signaling pathways (PI3K/AKT). However, silencing PI3K inhibited the abovementioned effects of acacetin. In conclusion, acacetin improved myocardial mitochondrial dysfunction through regulating oxidative stress, mitochondrial fission and fusion, and mitochondrial pathway apoptosis mediated by PI3K/AKT signaling pathway in hypertensive rats with IR.

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Data availability

Most of he data that support the findings of this study are available in the supplementary material of this article, others are available from the corresponding author upon reasonable request.

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Acknowledgements

The author of this article wishes to thank the National Key Research and Development Program (The Major Project for Research of the Modernization of TCM): (2019YFC1708802), Major Science and Technology Projects of Henan Province (171100310500), Henan Province high-level personnel special support “ZhongYuan One Thousand People Plan”-Zhongyuan Leading Talent (ZYQR201810080) , the Engineering and Technology Center for Chinese Medicine Development of Henan Province and the Ph.D. Research Funds of Henan University of Chinese Medicine (RSBSJJ2018-04).

Funding

This work was supported by the National Key Research and Development Program (The Major Project for Research of the Modernization of TCM): (2019YFC1708802), Major Science and Technology Projects of Henan Province (171100310500), Henan Province high-level personnel special support “ZhongYuan One Thousand People Plan”-Zhongyuan Leading Talent (ZYQR201810080), the Engineering and Technology Center for Chinese Medicine Development of Henan Province and the Ph.D. Research Funds of Henan University of Chinese Medicine (RSBSJJ2018-04).

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  1. Peipei Yuan and Qi Zhang contributed equally to the article.

Authors and Affiliations

  1. College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China

    Peipei Yuan, Qi Zhang, Yang Fu, Ying Hou, Liyuan Gao, Yaxin Wei, Weisheng Feng & Xiaoke Zheng

  2. The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, China

    Peipei Yuan, Weisheng Feng & Xiaoke Zheng

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  1. Peipei Yuan
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Yuan, P., Zhang, Q., Fu, Y. et al. Acacetin inhibits myocardial mitochondrial dysfunction by activating PI3K/AKT in SHR rats fed with fructose. J Nat Med 77, 262–275 (2023). https://doi.org/10.1007/s11418-022-01666-7

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