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.
Bibliographical noteFunding Information:
This work was supported by the Ministry of Food and Drug Safety (20182MFDS422, 20182MFDS425, 22214MFDS252), a National Research Foundation of Korea (NRF) grant funded by the Korea government, Ministry of Science (MEST; MRC 2010-0029355) (MISIT; No. MRC, 2017R1A5A2015541), and “Regional Innovation Strategy (RIS)” through the NRF funded by the Ministry of Education (MOE) (2021RIS-001).
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
- TMCA derivatives
- Tyrosine hydroxylase