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 in | Molecular neurobiology Vol. 60; no. 5; pp. 2737 - 2748 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.05.2023
Springer Nature B.V |
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| Abstract | 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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| AbstractList | 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. |
| Author | Kim, Mijin Hong, Eunchong Yun, Jaesuk Min, Hyun Kyu Lim, Heena Yayeh, Taddesse Gu, Sun Mi Jung, Jae-Chul Oh, Seikwan Jabborov, Abdulaziz Park, Woo-Kyu |
| Author_xml | – sequence: 1 givenname: Eunchong surname: Hong fullname: Hong, Eunchong organization: College of Pharmacy, Chungbuk National University – sequence: 2 givenname: Hyun Kyu surname: Min fullname: Min, Hyun Kyu organization: College of Pharmacy, Chungbuk National University – sequence: 3 givenname: Heena surname: Lim fullname: Lim, Heena organization: Department of Molecular Medicine, School of Medicine, Ewha Womans University – sequence: 4 givenname: Sun Mi surname: Gu fullname: Gu, Sun Mi organization: College of Pharmacy, Chungbuk National University – sequence: 5 givenname: Abdulaziz surname: Jabborov fullname: Jabborov, Abdulaziz organization: College of Pharmacy, Chungbuk National University – sequence: 6 givenname: Taddesse surname: Yayeh fullname: Yayeh, Taddesse organization: Department of Molecular Medicine, School of Medicine, Ewha Womans University – sequence: 7 givenname: Mijin surname: Kim fullname: Kim, Mijin organization: Department of Molecular Medicine, School of Medicine, Ewha Womans University – sequence: 8 givenname: Woo-Kyu surname: Park fullname: Park, Woo-Kyu organization: Medicinal Science Division, Korea Research Institute of Chemical Technology – sequence: 9 givenname: Jae-Chul surname: Jung fullname: Jung, Jae-Chul organization: Department of Molecular Medicine, School of Medicine, Ewha Womans University – sequence: 10 givenname: Jaesuk orcidid: 0000-0001-6228-3323 surname: Yun fullname: Yun, Jaesuk email: jyun@chungbuk.ac.kr organization: College of Pharmacy, Chungbuk National University – sequence: 11 givenname: Seikwan surname: Oh fullname: Oh, Seikwan email: skoh@ewha.ac.kr organization: Department of Molecular Medicine, School of Medicine, Ewha Womans University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36715919$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_celrep_2023_112776 crossref_primary_10_1111_1753_0407_13514 crossref_primary_10_1016_j_foodres_2024_114405 |
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| SubjectTerms | 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 |
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| Title | Derivatives of 3, 4, 5-Trimethoxycinnamic Acid Ameliorate Stress-Induced Anxiety in Mice and Rats |
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