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Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging

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Abstract

Background

Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats.

Methods and results

Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2–related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels.

Conclusions

GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.

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Data Availability

The data used and analyzed in this study are available from the Corresponding author on reasonable request.

Abbreviations

CVDs:

Cardiovascular diseases

GA:

Gallic acid

D-GAL:

D-galactose

SIRT1:

Sirtuin 1

PGC1-ɑ:

PPARγ coactivator 1-α

TFAM:

Transcription Factor A, Mitochondrial

Bcl2:

B-cell lymphoma protein 2

Bax:

(Bcl-2)-associated X

PINK:

PTEN induced putative kinase 1

Drp1:

Dynamin related protein 1

Mfn1:

Mitofusin-1

Mfn2:

Mitofusin-2

ROS:

Reactive oxygen species

NAD:

Nicotinamide adenine dinucleotide

CONT:

Control

CK-MB:

Creatine kinase

LDH:

Lactate dehydrogenase

MDA:

Malonic dialdehyde

SOD:

Superoxide dismutase

GPx:

Glutathione peroxidase

CAT:

Catalase

ELISA:

Enzyme-linked immunosorbent assay

qRT-PCR:

Quantitative Real-Time Polymerase chain reaction

HW:

Heart Weight

BW:

Body Weight

H&E:

Hematoxylin and eosin

SE:

Standard error

ANOVA:

Analysis of variance

WHW:

Whole Heart Weight

Nrf2:

Nuclear factor erythroid 2–related factor 2

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Acknowledgements

The authors would like to thank the Hamadan University of Medical Sciences for funding.

Funding

The study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 140005123991).

Author information

Authors and Affiliations

  1. Department of Physiology, School of medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Mohammad Zarei & Fatemeh Ramezani-Aliakbari

  2. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Mohammad Zarei, Abdolrahman Sarihi, Safoura Raoufi, Seyed Asaad Karimi & Fatemeh Ramezani-Aliakbari

  3. Department of Neuroscience, School of Sciences and Advanced Technology in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Abdolrahman Sarihi & Seyed Asaad Karimi

  4. Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Alireza Zamani

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Contributions

MZ: Investigation, Supervision, Project administration. AS: Conceptualization, Formal analysis, Writing - Review & Editing. AZ: Formal analysis, Writing - Review & Editing. SR: Investigation. SAK: Writing - Review & Editing. FRA: Conceptualization, Formal analysis, Investigation, Writing - Original Draft, Funding acquisition. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Fatemeh Ramezani-Aliakbari.

Ethics declarations

Ethics approval and consent to participate

Ethical approval was granted by the Ethics Committee of Hamadan University of Medical Sciences (Ethics Committee permission No. IR.UMSHA.REC.1400.270).

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None.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Preprint

The present study has been submitted to a preprint platform. DOI: https://doi.org/10.21203/rs.3.rs-2491748/v1, Posted Date: January 23rd, 2023, License: This work is licensed under a Creative Commons Attribution 4.0 International License.

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Zarei, M., Sarihi, A., Zamani, A. et al. Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging. Mol Biol Rep 50, 8005–8014 (2023). https://doi.org/10.1007/s11033-023-08670-4

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