Open Access

Guan Xin Dan Shen formulation protects db/db mice against diabetic cardiomyopathy via activation of Nrf2 signaling

  • Authors:
    • Bin Zhang
    • Chen-Yang Zhang
    • Xue-Lian Zhang
    • Gui-Bo Sun
    • Xiao-Bo Sun
  • View Affiliations

  • Published online on: May 25, 2021     https://doi.org/10.3892/mmr.2021.12170
  • Article Number: 531
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Guan Xin Dan Shen formulation (GXDSF) is a widely used treatment for the management of coronary heart disease in China and is composed of three primary components: Dalbergiae odoriferae Lignum, Salviae miltiorrhizae Radix et Rhizoma and Panax notoginseng Radix et Rhizoma. However, the potential use of GXDSF for the management of diabetic cardiomyopathy (DCM) has not been previously assessed. The present study aimed to assess the effects of GXDSF on DCM, as well as the underlying mechanism. In the present study, db/db mice were used. Following treatment with GXDSF for 10 weeks, fasting blood glucose, insulin sensitivity, serum lipid levels and cardiac enzyme levels were detected. Cardiac pathological alterations and cardiac function were assessed by performing hematoxylin and eosin staining and echocardiograms, respectively. TUNEL assays were conducted to assess cardiomyocyte apoptosis. Additionally, reverse transcription‑quantitative PCR and western blotting were performed to evaluate the expression of apoptosis‑associated genes and proteins, respectively. In the model group, the db/db mice displayed obesity, hyperlipidemia and hyperglycemia, accompanied by noticeable myocardial hypertrophy and diastolic dysfunction. Following treatment with GXDSF for 10 weeks, serum triglyceride levels were lower and insulin sensitivity was enhanced in db/db mice compared with the model group, which indicated improvement in condition. Cardiac hypertrophy and dysfunction were also improved in db/db mice following treatment with GXDSF, resulting in significantly increased left ventricular ejection fraction and fractional shortening compared with the model group. Following treatment with metformin or GXDSF, model‑induced increases in levels of myocardial enzymes were decreased in the moderate and high dose groups. Moreover, the results indicated that, compared with the model group, GXDSF significantly inhibited cardiomyocyte apoptosis in diabetic heart tissues by increasing Bcl‑2 expression and decreasing the expression levels of Bax, cleaved caspase‑3 and cleaved caspase‑9. Mechanistically, GXDSF enhanced Akt phosphorylation, which upregulated antioxidant enzymes mediated by nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling. Collectively, the results of the present study indicated that GXDSF attenuated cardiac dysfunction and inhibited cardiomyocyte apoptosis in diabetic mice via activation of Akt/Nrf2 signaling. Therefore, GXDSF may serve as a potential therapeutic agent for the management of DCM.
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July-2021
Volume 24 Issue 1

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Spandidos Publications style
Zhang B, Zhang C, Zhang X, Sun G and Sun X: Guan Xin Dan Shen formulation protects <em>db/db</em> mice against diabetic cardiomyopathy via activation of Nrf2 signaling. Mol Med Rep 24: 531, 2021
APA
Zhang, B., Zhang, C., Zhang, X., Sun, G., & Sun, X. (2021). Guan Xin Dan Shen formulation protects <em>db/db</em> mice against diabetic cardiomyopathy via activation of Nrf2 signaling. Molecular Medicine Reports, 24, 531. https://doi.org/10.3892/mmr.2021.12170
MLA
Zhang, B., Zhang, C., Zhang, X., Sun, G., Sun, X."Guan Xin Dan Shen formulation protects <em>db/db</em> mice against diabetic cardiomyopathy via activation of Nrf2 signaling". Molecular Medicine Reports 24.1 (2021): 531.
Chicago
Zhang, B., Zhang, C., Zhang, X., Sun, G., Sun, X."Guan Xin Dan Shen formulation protects <em>db/db</em> mice against diabetic cardiomyopathy via activation of Nrf2 signaling". Molecular Medicine Reports 24, no. 1 (2021): 531. https://doi.org/10.3892/mmr.2021.12170