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

Response of hippocampal Nrf2 gene expression and serum malondialdehyde levels to aerobic exercise and cannabidiol extract consumption in obese male Wistar rats

Articles in Press

Document Type : Original Article

Authors

Narges Kazemi Ashtiani 1
Hossein Abednatanzi 2
Mandana Gholami 3
Farshad Ghazalian 1
Farah Nameni 4

1 Department of Physical Education and Sport Sciences, SR.C., Islamic Azad University, Tehran, Iran

2 Assistant Prof., Dept. of Professional Physical Education and Sport Science, Science, and Research Branch, Islamic Azad University, Tehran, Iran

3 Department of Physical Education and Sport Sciences, SR.C., Islamic Azad University, Tehran, Iran.

4 Department of Exercise Physiology, VaP.C., Islamic Azad University, Varamin, Iran

10.22122/jeoct.2026.605947.1231
Abstract
Aerobic exercise and cannabidiol extract may modulate oxidative stress markers under high-fat diet conditions; however, their simultaneous effects on hippocampal Nrf2 gene expression and serum MDA in high-fat diet-induced obesity have not been examined. This study investigated six weeks of aerobic exercise and cannabidiol extract in obese male Wistar rats. Forty male Wistar rats were randomized into five groups (n = 8/group): healthy control, HFD, HFD+Tr, HFD+Sup, and HFD+Tr+Sup. HFD groups received a high-fat diet for two months before intervention. Aerobic training involved treadmill running for six weeks, five sessions/week. Cannabidiol extract was administered by gavage at 100 ng/kg. After intervention, rats were sacrificed; hippocampal Nrf2 gene expression and serum MDA were measured by Real-Time PCR and ELISA, respectively. Data were analyzed by one-way ANOVA with Tukey’s post hoc test. HFD significantly increased serum MDA and decreased hippocampal Nrf2 expression (p < 0.05). MDA was significantly higher in HFD and HFD+Tr than healthy control, but significantly lower in HFD+Sup and HFD+Tr+Sup than HFD (p < 0.05). Nrf2 expression was significantly higher in HFD+Sup and HFD+Tr+Sup than HFD, higher in both extract-treated groups than healthy control, and higher in HFD+Sup than HFD+Tr (p < 0.05). Cannabidiol extract, alone or combined with aerobic exercise, may partly reduce adverse high-fat-diet effects on oxidative status and improve antioxidant defense capacity. Further studies are necessary.

What is already known on this subject?

• High-fat diets are associated with oxidative stress, lipid peroxidation, and disturbances in hippocampal antioxidant signaling.

• Nrf2 is a major regulator of cellular antioxidant defense, whereas MDA is an important marker of lipid peroxidation.

• Aerobic exercise and cannabidiol have each been reported to modulate oxidative-stress-related pathways in experimental models.

 

What this study adds?

• In obese male Wistar rats, high-fat feeding significantly increased serum MDA and significantly reduced hippocampal Nrf2 gene expression.

• Cannabidiol extract, alone and combined with aerobic exercise, significantly reduced serum MDA compared with HFD and significantly increased hippocampal Nrf2 expression.

• Aerobic exercise alone did not significantly reduce MDA compared with HFD and did not significantly increase hippocampal Nrf2 expression in the reported comparisons.

Keywords

Aerobic exercise
Cannabidiol extract
Hippocampus
Oxidative stress
Obesity
Subjects

Organ Cross-Talk Tips:

  • Aerobic exercise and cannabidiol extract may exert systemic effects, linking hippocampal Nrf2 expression with circulating serum MDA levels.
  • The findings suggest a potential brain–blood crosstalk, where hippocampal antioxidant defense and peripheral oxidative stress markers respond to the same interventions.

Acknowledgements

This article reports part of the findings of a PhD dissertation completed in 2026. The authors thank the colleagues who assisted with the conduct of the study.

Funding

This study received no external funding. All research-related expenses were personally covered by the first author.

Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest the authors declare that there is no conflict of interest in the present research.

Ethical approval All procedures were conducted in accordance with institutional guidelines for laboratory-animal care and under approval of the ethics committee of the Science and Research Branch, Islamic Azad University, Tehran, Iran. Ethics approval code: IR.IAU.SRB.REC.1404.420.

Informed consent 

Not applicable; this was an animal study. 

Author contributions 

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

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Journal of Exercise & Organ Cross Talk

Articles in Press, Accepted Manuscript
Available Online from 01 January 2027

  • Receive Date 05 August 2026
  • Revise Date 03 August 2026
  • Accept Date 18 October 2026

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