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Atheroprotective and hepatoprotective effects of trans-chalcone through modification of eNOS/AMPK/KLF-2 pathway and regulation of COX-2, Ang-II, and PDGF mRNA expression in NMRI mice fed HCD

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Abstract

Background

The effects of trans-chalcone on atherosclerosis and NAFLD have been investigated. However, the underlying molecular mechanisms of these effects are not completely understood. This study aimed to deduce the impacts of trans-chalcone on the eNOS/AMPK/KLF-2 pathway in the heart tissues and the expression of Ang-II, PDFG, and COX-2 genes in liver sections of NMRI mice fed HCD.

Methods and results

Thirty-two male mice were divided into four groups (n = 8): control group; fed normal diet. HCD group; fed HCD (consisted of 2% cholesterol) (12 weeks). TCh groups; received HCD (12 weeks) besides co-treated with trans-chalcone (20 mg/kg and 40 mg/kg b.w. dosages respectively) for 4 weeks. Finally, the blood samples were collected to evaluate the biochemical parameters. Histopathological observations of aorta and liver sections were performed by H&E staining. The real-time PCR method was used for assessing the expression of the aforementioned genes. Histopathological examination demonstrated atheroma plaque formation and fatty liver in mice fed HCD which were accomplished with alteration in biochemical factors and Real-time PCR outcomes. Administration of trans-chalcone significantly modulated the serum of biochemical parameters. These effects were accompanied by significant increasing the expression of eNOS, AMPK, KLF-2 genes in heart sections and significant decrease in COX-2, Ang-II, and PDGF mRNA expression in liver sections.

Conclusion

Our findings propose that the atheroprotective and hepatoprotective effects of trans-chalcone may be attributed to the activation of the eNOS/AMPK/KLF-2 pathway and down-regulation of Ang-II, PDFG, and COX-2 genes, respectively.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. (https://doi.org/10.6084/m9.figshare.14748543).

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Acknowledgements

This study has been performed in the Laboratory Complex of the Science and Research Branch of Azad University.

Funding

The authors did not receive any funding from institutions or individuals for this research.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Mahsa Ale-Ebrahim & Leyla Karkhaneh

  2. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Raziyeh Rahmani & Niloofar Mohammadifar

  3. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Kousar Faryabi

  4. Department of Veterinary Pathology, Faculty of Specialized Veterinary, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Pejman Mortazavi

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  1. Mahsa Ale-Ebrahim
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  4. Niloofar Mohammadifar
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  5. Pejman Mortazavi
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Contributions

LK designed the study, analyzed the data, and wrote the manuscript; MA-E and LK supervised the study and PM revised the manuscript; RR, KF, NM performed the experiments. All authors have read and agreed to publish this manuscript.

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Correspondence to Mahsa Ale-Ebrahim or Leyla Karkhaneh.

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No potential conflict of interest relevant to this article was reported.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The animal protocol was authorized by the Science and Research Branch of the Islamic Azad University, Animal Ethics Committee (approval code: 176947). This study was carried out in the laboratory complex of the Science and Research Branch, Islamic Azad University, Tehran, Iran.

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Ale-Ebrahim, M., Rahmani, R., Faryabi, K. et al. Atheroprotective and hepatoprotective effects of trans-chalcone through modification of eNOS/AMPK/KLF-2 pathway and regulation of COX-2, Ang-II, and PDGF mRNA expression in NMRI mice fed HCD. Mol Biol Rep 49, 3433–3443 (2022). https://doi.org/10.1007/s11033-022-07174-x

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  • DOI: https://doi.org/10.1007/s11033-022-07174-x

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