Cinnamic aldehyde treatment alleviates chronic unexpected stress-induced depressive-like behaviors via targeting cyclooxygenase-2 in mid-aged rats
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Updated: Apr 19, 2026
The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Ying Yao1, Hai-Ying Huang2, Yuan-Xiao Yang3
1Pharmacy Department, Zhejiang Medical College, Hangzhou 310053, China.
Ethnopharmacological Relevance:
COX-2 has been considered as a potent molecular target for prevention and therapy of depression. However, a recent study showed that COX-2 inhibitor does not improve depressive symptoms in persons aged 70 and over. Therefore, whether treatments targeting COX-2 have a clinical efficacy in depression, especially elderly individuals, remains unclear. Cinnamic aldehyde is a major constituent of Cinnamomum cassia, which has exhibited excellent anti-inflammatory activities as a COX-2 inhibitor. To investigate the potential antidepressant effect of cinnamic aldehyde in mid-aged rats.
Materials And Methods:
The depressive-like behaviors were measured after the rats exposed to chronic unexpected mild stress (CUMS). Cinnamic aldehyde was administrated by oral gavage to stressed rats (22.5, 45, 90 mg/kg, respectively) for 21 days. The mRNA, protein expression and activity of cyclooxygenase-2 (COX-2), as well as prostaglandin E2 (PGE2) levels were measured in the frontal cortex and hippocampus of stressed animals.
Results:
We found that CUMS procedure not only decreased the sucrose preference, but also elevated the COX-2 activity, mRNA and protein levels, and increased PGE2 concentration in rat brain regions. Treatment with high doses of cinnamic aldehyde (45, 90 mg/kg) reversed the behavioral abnormalities, and decreased the COX-2 protein and activity (but not COX-2 mRNA expression) and PGE2 concentration in frontal cortex and hippocampus of stressed rats.
Conclusion:
Cinnamic aldehyde exerted antidepressant-like effects in stressed mid-aged rats, and its mechanism of action appears to decrease COX-2 protein and activity. The current findings suggest that targeting COX-2 system might be benefit to the depression, especially elderly individuals and cinnamic aldehyde might be a promising medicine to treat the subjects in the depression.
Insights
Cinnamic aldehyde shows antidepressant effects in stressed rats by reducing cyclooxygenase-2 (COX-2) activity. This suggests potential for treating depression, particularly in elderly individuals.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Cyclooxygenase-2 (COX-2) is a target for depression therapy, but efficacy in the elderly is uncertain.
- Cinnamic aldehyde, a COX-2 inhibitor from Cinnamomum cassia, has anti-inflammatory properties.
- Investigating cinnamic aldehyde's antidepressant potential in mid-aged rats is crucial.
Purpose of the Study:
- To evaluate the antidepressant-like effects of cinnamic aldehyde in a rat model of depression.
- To explore the mechanism of action involving cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2).
Main Methods:
- Rats were subjected to chronic unpredictable mild stress (CUMS) to induce depressive-like behaviors.
- Cinnamic aldehyde was administered orally to stressed rats for 21 days.
- COX-2 activity, mRNA, protein expression, and PGE2 levels were measured in the frontal cortex and hippocampus.
Main Results:
- CUMS decreased sucrose preference and increased COX-2 activity, protein, mRNA, and PGE2 levels.
- High doses of cinnamic aldehyde (45, 90 mg/kg) reversed behavioral deficits.
- Cinnamic aldehyde reduced COX-2 protein, activity, and PGE2 levels, but not COX-2 mRNA expression.
Conclusions:
- Cinnamic aldehyde demonstrates antidepressant-like effects in stressed rats.
- The mechanism involves the downregulation of COX-2 protein and activity.
- Cinnamic aldehyde may be a promising therapeutic agent for depression, especially in the elderly.
