**1. Introduction**

Depression is a widespread chronic psychiatric disease, characterized by low mood, lack of energy, sadness, insomnia, and high morbidity, that affects more than 300 million people worldwide [1,2]. This illness can affect anyone, regardless of age, sex, social status, education, nationality or ethnic origin [3,4]. It is the leading cause of disability and is directly associated with a remarkable number of suicides cases around the world [5,6].

Despite the physiopathological mechanism of depression remaining not widely elucidated and unclear, numerous studies have shown a multifactorial origin, involving genetics, environmental, psychological, and social factors, as well as dysfunction in multiple brain areas such as the hippocampus, prefrontal cortex, nucleus accumbens, and amygdale [7–10]. Recent findings of the presence of inflammatory process and oxidative stress in the pathophysiology of depression provide new pathways and treatment targets for improvement of pharmacological approach in depression [11]. Recently, Réus et al. (2019) have reported a microglial activation with formation of intracellular multiprotein complexes, the inflammasomes, which in turn activate interleukin-1β (IL-1β) that leads to a significant increase in the production and expression of tumor necrosis factor-α (TNF-α), IL-1β, reactive species of oxygen (ROS), and nitric oxide (NO) [12]. This finding is in accordance with a previous study performed by Oglodek (2017), in which it was identified that major depressive disorders, associated or not to posttraumatic stress disorder, present changes in the cytokines and increased oxidative stress [13].

Although efforts to increase knowledge and skills for healthcare providers have been made, depression remains both underdiagnosed and undertreated [14]. Actually, the therapeutics tools used in the treatment of depression have not produced satisfactory outcomes as necessary novel strategies to improve treatment outcomes [15,16]. Figure 1 summarizes the main mechanisms of action of antidepressant drugs.

**Figure 1.** Mechanisms of action of antidepressant drugs.

Natural products have been important sources of new drugs against various pathologies. Reports of antidepressant activity on these compounds indicate that they may be an alternative treatment option for depression [17]. Cinnamic acids are a group of aromatic carboxylic acids with carbonic skeleton C6–C3 (Figure 2) found in a variety of plants and foods, for which the biosynthetic route can generate several secondary metabolites such as coumarins, lignans, isoflavonoids, flavonoids, and others natural products [18].Cinnamic acids and their derivatives have attracted the attention of researchers due to their wide distribution in nature, low toxicity, structural diversity, and pharmacological actions [19], as anti-inflammatory [20], antioxidant [21], antitumor [22], hypoglycemic [23], antidepressant [24], and cytoprotective actions of neuroinflammation in neurodegenerative diseases [25]. Considering the importance of cinnamic acids as bioactive substances and their presence in various foods and medicinal plants, this review discusses the antidepressant action mechanisms of these compounds, demonstrating their therapeutic potential for depressive disorders.

**Figure 2.** Chemical structure of cinnamic acid.
