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E1231 Alleviates Diabetic Cardiomyopathy by Regulating the Silent Information Regulator 1/Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α/Nuclear Factor Erythroid 2-Related Factor 2 Pathway

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Pharmaceutical Chemistry Journal Aims and scope

We aimed to investigate the underlying function and mechanism of E1231 against diabetic cardiomyopathy (DCM). H9c2 cells were exposed to either 33 mmol/L mannitol or an identical concentration of glucose (high glucose, HG) in vitro. In vivo, diabetes mellitus (DM) mice were induced by injection of 60 mg/kg streptozotocin intraperitoneally. E1231 was used to treat cells (5 mmol/L) or animals (40 mg/kg), and subsequent assays were conducted to determine its effect on DCM-associated manifestations. Western blot was employed to evaluate protein expressions of the silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). In vitro, treatment with E1231 significantly reduced oxidative stress and apoptosis induced by HG via activating the SIRT1-PGC-1α/Nrf2 pathway in H9c2 cells, compared to cardiomyocytes under HG conditions. In vivo, DM mice showed up-regulated SIRT1, PGC-1α, and Nrf2 expression, with protection against cardiac fibrosis, dysfunction, and oxidative stress impairment. The study demonstrated that E1231 alleviates cardiac dysfunction via activating the SIRT1-PGC-1α signaling pathway in DCM, leading to the activation of Nrf2. Therefore, E1231 has the potential to facilitate the treatment of DCM.

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Authors and Affiliations

  1. Department of Clinical Laboratory, the First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China

    Yunxia Cui & Hongjun Lou

  2. Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom

    Qi Guo

  3. Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

    Guiyun Qi

  4. Department of the Fourth Orthopedics, the First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China

    ** Gao

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  1. Yunxia Cui
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  2. Hongjun Lou
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  3. Qi Guo
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  4. Guiyun Qi
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  5. ** Gao
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Correspondence to ** Gao.

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Yunxia Cui and Hongjun Lou are co-first authors.

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Cui, Y., Lou, H., Guo, Q. et al. E1231 Alleviates Diabetic Cardiomyopathy by Regulating the Silent Information Regulator 1/Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α/Nuclear Factor Erythroid 2-Related Factor 2 Pathway. Pharm Chem J 58, 227–237 (2024). https://doi.org/10.1007/s11094-024-03138-6

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  • DOI: https://doi.org/10.1007/s11094-024-03138-6

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