Derivatives of 3, 4, 5-Trimethoxycinnamic Acid Ameliorate Stress-Induced Anxiety in Mice and Rats

Stress is an overwhelming problem associated with neuronal damage leading to anxiety and depression. The compound 3, 4, 5-trimethoxycinnamic acid (TMCA) has shown anti-stress effects; however, its derivatives remained unknown for their anxiolytic properties. Here, therefore, we investigated derivati...

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Published inMolecular neurobiology Vol. 60; no. 5; pp. 2737 - 2748
Main Authors Hong, Eunchong, Min, Hyun Kyu, Lim, Heena, Gu, Sun Mi, Jabborov, Abdulaziz, Yayeh, Taddesse, Kim, Mijin, Park, Woo-Kyu, Jung, Jae-Chul, Yun, Jaesuk, Oh, Seikwan
Format Journal Article
LanguageEnglish
Published New York Springer US 01.05.2023
Springer Nature B.V
Subjects
Amygdala
Animals
Anti-Anxiety Agents - pharmacology
Anti-Anxiety Agents - therapeutic use
Anxiety
Anxiety - drug therapy
Biomedical and Life Sciences
Biomedicine
Cell Biology
Dopamine
Extracellular signal-regulated kinase
Immobilization
Mice
Neurobiology
Neurology
Neurons
Neurosciences
Pheochromocytoma cells
Protein expression
Rats
Serotonin receptors
Stress
Tyrosine 3-monooxygenase
TMCA derivatives
Tyrosine hydroxylase
Stress
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Summary:Stress is an overwhelming problem associated with neuronal damage leading to anxiety and depression. The compound 3, 4, 5-trimethoxycinnamic acid (TMCA) has shown anti-stress effects; however, its derivatives remained unknown for their anxiolytic properties. Here, therefore, we investigated derivatives of TMCA (dTMCA) for their anxiolytic effects using immobilization and electric shock-induced stress in rats. Derivatives of TMCA ameliorated anxiety in mice and rats revealed by extended period of time spent in the open arms of elevated plus maze. Stress-mediated repression of tyrosine hydroxylase (TH) protein expression in the amygdala regions of rat brain and dopamine levels in the PC12 cells was restored by two selected derivatives (TMCA#5 and TMCA#9). Unlike TH expression, stress-induced protein expression of phospho-extracellular signal-regulated kinase (pERK) was unaffected by both derivatives in rats. Given the preferential inhibitory activity of dTMCA on dopamine and serotonin receptors, serotonergic road map of cellular signaling could be their target for anxiolytic effects. Thus, dTMCA would be promising agents to prevent neuronal damage associated with rampant stressful conditions.
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ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-023-03240-y