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.

压力是与导致焦虑和抑郁的神经元损伤相关的压倒性问题。化合物3,4,5-三甲氧基肉桂酸（TMCA）显示出抗应激作用；然而，其衍生物的抗焦虑特性仍然未知。因此，在这里，我们研究了 TMCA (dTMCA) 的衍生物在大鼠中使用固定化和电击诱导的压力的抗焦虑作用。TMCA 的衍生物改善了小鼠和大鼠的焦虑，这是通过延长在高架十字迷宫的张开臂​​中度过的时间来揭示的。两种选定的衍生物（TMCA#5 和 TMCA#9）恢复了大鼠大脑杏仁核区域应激介导的酪氨酸羟化酶 (TH) 蛋白表达抑制和 PC12 细胞中的多巴胺水平。与 TH 表达式不同，在大鼠中，应激诱导的磷酸细胞外信号调节激酶 (pERK) 蛋白表达不受这两种衍生物的影响。鉴于 dTMCA 对多巴胺和血清素受体的优先抑制活性，细胞信号转导的血清素能路线图可能是它们抗焦虑作用的目标。因此，dTMCA 将是有前途的药物，用于预防与猖獗的压力条件相关的神经元损伤。