Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Impact of borage extract and 8-week aerobic training on liver autophagy genes Beclin-1 and Parkin in male Wistar rats with NAFLD

Document Type : Original Article

Authors

Atena Bakhshizadeh 1
Hossein Abed Natanzi 2
Mandana Gholami 2
Farshad Ghazalian 2

1 Ph.D. student of physical Education Sport sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

2 Department of physical Education Sport sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

https://doi.org/10.22122/jeoct.2025.501185.1140
Abstract
NAFLD is one of the chronic liver diseases closely related to metabolic disorders. Borage and physical activity improves oxidative indices. Also, Beclin-1 is a key gene in the autophagy process, and Parkin acts as a protective mechanism against liver damage. So, this study aims to investigate the effect of aerobic training and borage extract on the expression of Beclin-1 and Parkin genes in the liver cells in NAFLD. In this experimental study,40male Wistar rats weighing were divided into 4groups. (control, supplement, training), and training+supplement. The data were analyzed using SPSS 25 software. Training and borage extract had no significant effect on Beclin-1 expression (P=0.267), with fold changes of 1.05±0.07 for training, 1.07±0.06 for borage extract, and 1.12±0.08 for training+borage extract, compared to the control. However, Parkin expression increased significantly (P=0.006), with fold changes of 1.15±0.08 for Training, 1.18±0.09 for borage extract, and 1.20±0.10 for training+borage extract. Post hoc confirmed a significant increase in Parkin expression in the training+borage extract group compared to the control (P=0.035). This study showed that it is possible that the consumption of borage extract and aerobic training together and alone have an increasing the expression of Parkin. So, both borage extract and aerobic training have individual benefits for improving liver health by targeting Beclin-1 and PARKIN pathways, and their combination could provide a more robust approach to managing NAFLD by promoting effective autophagy, mitophagy, and mitochondrial function. This dual intervention could reduce liver damage, inflammation, and fibrosis, ultimately improving metabolic outcomes in individuals suffering from NAFLD.

What is already known on this subject?

Non-alcoholic fatty liver disease is one of the chronic liver diseases closely related to metabolic disorders.  

What this study adds?

 

Aerobic exercise can reduce oxidative stress, inflammation, and apoptosis, which can improve the severity of the disease in people with NAFLD.

Keywords

Aerobic training
Borage extract
Autophagy
Beclin-1
Parkin
NAFLD

Subjects

Acknowledgements

None.

Funding

None.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval This study has the code of ethics from the Ethics Committee of Islamic Azad University, Tehran, Iran (ethical code: IR.IAU.SRB.REC.1401.194).

Informed consent Animal study

Author contributions

Conceptualization: A.B., H.A.N., M.Gh, F.Gh.; Methodology: A.B., H.A.N., M.Gh, F.Gh.; Software: H.A.N.; Validation: A.B. Formal analysis: M.Gh.; Investigation: F.Gh.; Resources: A.B., H.A.N., M.Gh, F.Gh.; Data curation: A.B., H.A.N.; Writing - original draft: A.B.; Writing – review & editing: M.Gh.; Visualization: F.Gh.; Supervision: H.A.N. Project administration: H.A.N.; Funding acquisition: H.A.N

An, X., Liu, J., Li, Y., Dou, Z., Li, N., Suo, Y., Ma, Y., Sun, M., Tian, Z., & Xu, L. (2021). Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway. Peptides, 135, 170422. https://doi.org/10.1016/j.peptides.2020.170422   
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012). Lack of exercise is a major cause of chronic diseases. Comprehensive physiology, 2(2), 1143. doi: https://doi.org/10.1002/cphy.c110025
Chen, J., Jian, L., Guo, Y., Tang, C., Huang, Z., & Gao, J. (2024). Liver Cell Mitophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis. Antioxidants, 13(6), 729. https://doi.org/10.3390/antiox13060729
Chun, S. K., Lee, S., Yang, M.-J., Leeuwenburgh, C., & Kim, J.-S. (2017). Exercise-induced autophagy in fatty liver disease. Exercise and sport sciences reviews, 45(3), 181-186. https://doi.org/ 10.1249/JES.0000000000000116
DP, N. (2010). PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol, 8, e1000298.  
Edmunds, L. R., Xie, B., Mills, A. M., Huckestein, B. R., Undamatla, R., Murali, A., Pangburn, M. M., Martin, J., Sipula, I., & Kaufman, B. A. (2020). Liver-specific Prkn knockout mice are more susceptible to diet-induced hepatic steatosis and insulin resistance. Molecular Metabolism, 41, 101051. https://doi.org/10.1016/j.molmet.2020.101051
Farzanegi, P., & Abbaszadeh, H. (2022). Evaluation of BECLINE-1 and LC3 gene expression in endometriosis rats following regular aerobic exercise and omega-3 intake. Nurse and Physician Within War, 10(34), 50-57. https://doi.org/http://dx.doi.org/10.29252/npwjm.10.34.50
 Ghareghani, P., Shanaki, M., Ahmadi, S., Khoshdel, A. R., Rezvan, N., Meshkani, R., Delfan, M., & Gorgani-Firuzjaee, S. (2018). Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice. Obesity research & clinical practice, 12(1), 80-89. https://doi.org/10.1016/j.orcp.2017.01.004
Gunadi, J. W., Tarawan, V. M., Ray, H. R. D., Wahyudianingsih, R., Lucretia, T., Tanuwijaya, F., Lesmana, R., Supratman, U., & Setiawan, I. (2020). Different training intensities induced autophagy and histopathology appearances potentially associated with lipid metabolism in wistar rat liver. Heliyon, 6(5). https://doi.org/10.1016/j.heliyon.2020.e03874
Hedayati, K., Azarbayjani, M., Banaeifar, A., & Arshadi, S. (2019). The effect of aerobic training and adenosine on the expression of SREBP-1c and A1 receptor in hepatic fat-fed rats.
Ibrahim, R. M., & Alshammaa, D. A. S. (2023). Pharmacological aspects of Borago officinalis (Borage): A review article. Iraqi Journal of Pharmaceutical Sciences, 32(1), 1-13. https://doi.org/10.31351/vol32iss1pp1-13
Keating, S. E., George, J., & Johnson, N. A. (2015). The benefits of exercise for patients with non-alcoholic fatty liver disease. Expert review of gastroenterology & hepatology, 9(10), 1247-1250. https://doi.org/10.1586/17474124.2015.1075392
Khatri, S., Yadav, S., & Sharma, V. (2012). Importance of γ-linolenic acid in clinical indications. Int J Ther Appl, 2, 33-42.
Lemus-Conejo, A., Grao-Cruces, E., Toscano, R., Varela, L. M., Claro, C., Pedroche, J., Millan, F., Millan-Linares, M. C., & Montserrat-de La Paz, S. (2020). A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice. Food & function, 11(4), 2943-2952. https://doi.org/DOI: https://doi.org/10.1039/d0fo00206b  
Lemus-Conejo, A., Millan-Linares, M. d. C., Toscano, R., Millan, F., Pedroche, J., Muriana, F. J., & Montserrat-de la Paz, S. (2022). GPETAFLR, a peptide from Lupinus angustifolius L. prevents inflammation in microglial cells and confers neuroprotection in brain. Nutritional Neuroscience, 25(3), 472-484. https://doi.org/10.1080/1028415X.2020.1763058
Liang, Y., Zhang, Z., Tu, J., Wang, Z., Gao, X., Deng, K., El-Samahy, M., You, P., Fan, Y., & Wang, F. (2021). γ-Linolenic acid prevents lipid metabolism disorder in palmitic acid-treated alpha mouse liver-12 cells by balancing autophagy and apoptosis via the LKB1-AMPK-mTOR pathway. Journal of agricultural and food chemistry, 69(29), 8257-8267. doi: https://doi.org/10.1021/acs.jafc.1c02596
Ma, X., McKeen, T., Zhang, J., & Ding, W.-X. (2020). Role and mechanisms of mitophagy in liver diseases. Cells, 9(4), 837. doi: https://doi.org/10.3390/cells9040837
Mäkelä, T. N., Tuomainen, T.-P., Hantunen, S., & Virtanen, J. K. (2022). Associations of serum n–3 and n–6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease. The American Journal of Clinical Nutrition, 116(3), 759-770. https://doi.org/10.1093/ajcn/nqac150
Mustonen, A.-M., & Nieminen, P. (2023). Dihomo-γ-linolenic acid (20: 3n-6)—Metabolism, derivatives, and potential significance in chronic inflammation. International journal of molecular sciences, 24(3), 2116. Doi: https://doi.org/10.3390/ijms24032116
Naghdi Badi, H., Soroshzadeh, A., Rezazadeh, S., Sharifi, M., Ghalavand, A., & Omidi, H. (2007). Review on borage (valuable medicinal plant and the richest plant source of gamma linolenic acid). Journal of Medicinal Plants, 6(24), 1-16. https://dor.isc.ac/dor/20.1001.1.2717204.2007.6.24.1.8
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008). Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. The Journal of cell biology, 183(5), 795-803. https://doi.org/10.1083/jcb.200809125
Ok, D.-P., Ko, K., & Bae, J. Y. (2018). Exercise without dietary changes alleviates nonalcoholic fatty liver disease without weight loss benefits. Lipids in health and disease, 17, 1-7. https://doi.org/10.1186/s12944-018-0852-z
Rosa, M. E. (2016). Autophagy Regulation after Diet and Exercise in Non-alcoholic Fatty Liver Disease
Shewale, S. V., Boudyguina, E., Zhu, X., Shen, L., Hutchins, P. M., Barkley, R. M., Murphy, R. C., & Parks, J. S. (2015). Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver. Journal of lipid research, 56(6), 1191-1205. https://doi.org/10.1194/jlr.M059170
Taji, F., Mohseni Kouchesfehani, H., Sheikholeslami, F., Baesi, K., Motavalli, F., & Abdoli, A. (2017). Induction of Autophagy by the Beclin 1 Gene and Its Effect on MDCK Cell Line Necrosis. Pathobiology Research, 20(1), 1-15.
Undamatla, R., Fagunloye, O., Chen, J., Edmunds, L., Murali, A., Mills, A., Xie, B., Pangburn, M., Sipula, I., & Gibson, G. (2023). Reduced mitophagy is an early feature of NAFLD and liver-specific PARKIN knockout hastens the onset of steatosis, inflammation and fibrosis. Scientific Reports, 13(1), 7575. https://doi.org/10.1038/s41598-023-34710-x
Urrestarazu, M., Gallegos-Cedillo, V. M., Ferrón-Carrillo, F., Guil-Guerrero, J. L., Lao, M. T., & Álvaro, J. E. (2019). Effects of the electrical conductivity of a soilless culture system on gamma linolenic acid levels in borage seed oil. PLoS One, 14(2), e0207106. https://doi.org/10.1371/journal.pone.0207106
Wang, H., Ni, H.-M., Chao, X., Ma, X., Rodriguez, Y. A., Chavan, H., Wang, S., Krishnamurthy, P., Dobrowsky, R., & Xu, D.-X. (2019). Double deletion of PINK1 and Parkin impairs hepatic mitophagy and exacerbates acetaminophen-induced liver injury in mice. Redox biology, 22, 101148. https://doi.org/10.1016/j.redox.2019.101148
Williams, J. A., & Ding, W.-X. (2015). Targeting Pink1-Parkin-mediated mitophagy for treating liver injury. Pharmacological research, 102, 264-269. https://doi.org/doi:10.1016/j.phrs.2015.09.020
Williams, J. A., Ni, H.-M., Ding, Y., & Ding, W.-X. (2015). Parkin regulates mitophagy and mitochondrial function to protect against alcohol-induced liver injury and steatosis in mice. American journal of physiology-gastrointestinal and liver physiology, 309(5), G324-G340. https://doi.org/doi:10.1152/ajpgi.00108.2015
Zamansoltani, F., Nassiri-Asl, M., Karimi, R., & Mamaghani-Rad, P. (2008). Hepatotoxicity effects of aqueous extract of Echium amoenum in rats. Pharmacologyonline, 1, 432-438.
Zarringol, M. (2016). An overview of autophagy control by ROS (reactive oxygen species). Razi Journal of Medical Sciences, 24(164). http://rjms.iums.ac.ir/article-1-5038-en.html
Journal of Exercise & Organ Cross Talk
Volume 4, Issue 4
Autumn 2024
Pages 255-262

  • Receive Date 21 October 2024
  • Revise Date 26 December 2024
  • Accept Date 26 December 2024

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