Combination of quercetin and exercise training attenuates depression in rats with 1,2‐dimethylhydrazine‐induced colorectal cancer: Possible involvement of inflammation and BDNF signalling
Abstract
New Findings: What is the central question of this study? What are the alleviative effects of the combination of exercise training and quercetin supplementation on colorectal cancer‐related depression in rats with 1,2‐dimethylhydrazine‐induced colorectal cancer and what is the corresponding signalling pathway? What is the main finding and its importance? We showed that the combination of exercise training and quercetin supplementation resulted in a significant decrease in tumour incidence and improvement in depressive‐like behaviours through modulation of the BDNF/TrKβ/β‐catenin axis in the prefrontal cortex. In addition to physical problems, depression is considered to be one of the most important challenges for patients with various types of cancers, particularly colorectal cancer. Inflammation and upregulation of brain neurotrophic factors are two major links between cancer and depression. In this study, we aimed to evaluate the alleviative effects of quercetin and exercise training on depressive‐like behaviours in rats with 1,2‐dimethylhydrazine (DMH)‐induced colorectal cancer and to investigate the underlying mechanisms. Animals were assigned into the following five groups: (i) control group; (ii) DMH (20 mg kg−1s.c., once a week for 10 weeks); (iii) DMH for 10 weeks, followed by quercetin (50 mg kg−1p.o., once per week) for 12 weeks; (iv) DMH for 10 weeks, followed by exercise training for 12 weeks; and (v) DMH for 10 weeks, followed by quercetin and exercise training for 12 weeks. The DMH‐treated rats showed an increase in depressive‐like behaviours in both open field and forced swimming tests. Histopathological examination revealed neural damage and reduced Nissl bodies in the prefrontal cortex. In addition, administration of DMH increased inflammatory cytokines in the serum, prefrontal cortex and tumour tissues and decreased the expression levels of brain‐derived neurotrophic factor (BDNF), tyrosine kinase β receptor (TrKβ) and β‐catenin in the cortex. In contrast, treatment with quercetin and exercise training effectively alleviated all the above‐mentioned DMH‐associated behavioural, biochemical and histopathological alterations without changing its anti‐tumour activity. Taken together, our results show that the combination of quercetin and exercise training exerts potent anti‐tumour and anti‐depressive effects through suppression of inflammation and upregulation of the BDNF/TrKβ/β‐catenin axis in the prefrontal cortex.
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Intake of quercetin combined with physical activity exerts an antidepressant effect by suppressing inflammatory pathways and regulating BDNF.
“Intake of quercetin combined with physical activity exerts an antidepressant effect by suppressing inflammatory pathways and regulating the brain-derived neurotrophic factors (BDNF).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Sadighparvar et al. 2020
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- Authors
- Sadighparvar, S., Darband, S. G., Yousefi, B., Kaviani, M., Ghaderi‐Pakdel, F., Mihanfar, A., Babaei, G., Mobaraki, K., & Majidinia, M.
- Affiliations
- Urmia University of Medical Sciences (IR)
- Tabriz University of Medical Sciences (IR)
- Acadia University (CA)
- Neurophysiology Research Center Urmia University of Medical Sciences Urmia Iran
- Urmia University (IR)
- Corresponding author
- Majidinia, Maryam
- ORCID
- Venue
- Experimental Physiology
- Publisher
- Wiley
- Published
- 2020-08
- Volume
- 105
- Issue
- 9
- Pages
- 1598-1609
- ISSN
- 0958-0670 (ISSN-L)
- 1469-445X
- OpenAlex
- W3043043206
- Semantic Scholar
- 1c84bd1ed89902ce6dc5a07a8d804493ae50efe2
- Cited by
- 41
- References
- 46
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 3 · 2020: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- quercetin, exercise training, depression, colorectal cancer, 1,2-dimethylhydrazine, cancer-related depression, prefrontal cortex, neuroinflammation, inflammatory cytokines, neuroprotection, tumor incidence, depression-like behavior, combination therapy, flavonoids, brain-derived neurotrophic factor
- MeSH terms
- Animals, Depression, Male, Physical Conditioning, Animal, Quercetin, Colorectal Neoplasms, Signal Transduction, Cytokines, Rats, Wistar, Prefrontal Cortex, Brain-Derived Neurotrophic Factor, 1,2-Dimethylhydrazine, Receptor, trkB, beta Catenin, Rats
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