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Unlocking the potential: Baicalin's apoptosis-reducing power and activation of NRF2/P62 for alleviating diabetic cardiomyopathy in rats

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Abstract

Background

Baicalin has been proven to have the potential to reduce apoptosis and diabetic cardiomyopathy (DCM). However, the mechanism behind this effect still needs to be fully understood.

Objectives

To explore the potential therapeutic properties of Baicalin in managing DCM and controlling glycemic levels.

Results

In this study, Baicalin (at doses of 20, 60, or 120 mg/kg/d) were used to treat diabetic rats. At the end of treatment, the heart function of the rats was assessed. Furthermore, their serum levels of TG, TC, and LDL were measured using the ELISA method. Cell viability was evaluated using the CCK8 assay and apoptosis was assessed using flow cytometry or TUNEL assay. Primary cardiomyocytes were infected with NRF2 siRNA and then treated with Baicalin while incubating with high glucose (25 mmol/L). Protein and mRNA variations were analyzed using Western blot and qRT-PCR, respectively. The study found that when given Baicalin, diabetic rats demonstrated improved heart function. Without treatment, the hearts of diabetic rats displayed elevated levels of apoptotic cell death and cardiomyocyte autophagy, as well as decreased expressions of NRF2, HO-1, and KEAP1. However, Baicalin was able to reverse all of these diabetes-induced biochemical changes. Treatment enhanced NRF2 nuclear transfer, reduced hyperglycemia-induced apoptosis and autophagy in primary cardiomyocytes, and improved cellular viability in in vitro experiments. It must be noted that the protective effects of Baicalin were only observed when the Nrf2 gene expression was present in primary cardiomyocytes.

Conclusion

Baicalin may reduce the effects of DCM by activating NRF2 through KEAP1 suppression and regulating autophagy activation.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author by reasonable request.

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Acknowledgements

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Funding

We are very grateful to the Chongqing Hospital of Traditional Chinese Medicine for its financial support for this project.

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Authors and Affiliations

  1. Department of Endocrinology, Chongqing Hospital of Traditional Chinese Medicine, No. 6 Qizhi Road, Panxi, Jiangbei District, Chongqing, 400021, People’s Republic of China

    Wanling Wang, Rui Han, Li Lai & Xia Zhang

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  1. Wanling Wang
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  2. Rui Han
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  3. Li Lai
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  4. Xia Zhang
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Contributions

Research study design: XZ, Experiment conduction: WW, Data acquisition: RH, Data analysis: LL, Manuscript writing: XZ.

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Correspondence to Xia Zhang.

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Wanling Wang declares that she has no conflict of interest, Rui Han declares that she has no conflict of interest, Li Lai declares that she has no conflict of interest, Xia Zhang declares that she has no conflict of interest.

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All the experimental procedures were performed in accordance with the ethical standards stipulated by the International Committee of Medical Journal Editors.

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Wang, W., Han, R., Lai, L. et al. Unlocking the potential: Baicalin's apoptosis-reducing power and activation of NRF2/P62 for alleviating diabetic cardiomyopathy in rats. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-024-00434-w

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