Antidepressant Potential of Cinnamic Acids: Mechanisms of Action and Perspectives in Drug Development

Diniz, Lúcio Ricardo Leite; Souza, Marília Trindade de Santana; Barboza, Joice Nascimento; Almeida, Reinaldo Nóbrega de; Sousa, Damião Pergentino de

doi:10.3390/molecules24244469

Cited by 23 publications

(17 citation statements)

References 55 publications

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“…Overall, the two most probable candidates found by our workflow were caffeic acid and zileuton (Figure 3d). However, search of recently published literature indicated that caffeic acid has already been purposed to treat depression [26], so this compound was not investigated further. Our only candidate for experimental validation was found to be zileuton; (±)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea, which could inhibit 5-lipoxygenase among other function (Supplementary Table S2).…”

Section: Filtered Phase Resultsmentioning

confidence: 99%

Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach

et al. 2020

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Repurposing drugs to target M1 macrophages inflammatory response in depression constitutes a bright alternative for commonly used antidepressants. Depression is a significant type of mood disorder, where patients suffer from pathological disturbances associated with a proinflammatory M1 macrophage phenotype. Presently, the most commonly used antidepressants such as Zoloft and Citalopram can reduce inflammation, but suffer from dangerous side effects without offering specificity toward macrophages. We employed a new strategy for drug repurposing based on the integration of RNA-seq analysis and text mining using deep neural networks. Our system employs a Google semantic AI universal encoder to compute sentences embedding. Sentences similarity is calculated using a sorting function to identify drug compounds. Then sentence relevance is computed using a custom-built convolution differential network. Our system highlighted the NRF2 pathway as a critical drug target to reprogram M1 macrophage response toward an anti-inflammatory profile (M2). Using our approach, we were also able to predict that lipoxygenase inhibitor drug zileuton could modulate NRF2 pathway in vitro. Taken together, our results indicate that reorienting zileuton usage to modulate M1 macrophages could be a novel and safer therapeutic option for treating depression.

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Section: Filtered Phase Resultsmentioning

confidence: 99%

Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach

et al. 2020

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“…Ferulic acid and cinnamic acid have been found to have antidepressant effects in some studies [ 17 , 18 ], while quercetin and hydroxytyrosol demonstrated an approved anxiolytic effect [ 19 , 20 ]. Those compounds could be behind the observed effect.…”

Section: Discussionmentioning

confidence: 99%

“…The effectiveness of an antioxidant can be exerted in different forms, such as the scavenging of free radicals, the decomposition of free radicals, and also the chelation of metal ions [ 17 ]. This activity can be evaluated by FRAP and DPPH assays, the latter of which, due to its rapidity, is often used to screen molecules present in plant extracts [ 18 ]. Our results showed antioxidant activity in the phenolic extract of parsley.…”

Section: Discussionmentioning

confidence: 99%

The Potential of Parsley Polyphenols and Their Antioxidant Capacity to Help in the Treatment of Depression and Anxiety: An In Vivo Subacute Study

et al. 2021

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Depression and anxiety are major mental health problems in all parts of the world. These illnesses are associated with a number of risk factors, including oxidative stress. Psychotropic drugs of a chemical nature have demonstrated several side effects that elevated the impact of those illnesses. Faced with this situation, natural products appear to be a promising alternative. The aim of this study was to evaluate the anxiolytic and antidepressant effects of the Petroselinum sativum polyphenols in vivo, as well as its correlated antioxidant properties in vitro. Anxiolytic activity of the extract (50 and 100 mg/kg) was evaluated using the open field and the light-dark chamber tests, while the antidepressant activity was evaluated using the forced swimming test. The antioxidant activity of the extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical test and the FRAP (iron-reducing capacity) test. The phenolic extract showed very powerful anxiolytic and antidepressant-like effects, especially at a dose of 100 mg/kg, decreasing the depressive behavior in mice (decreased immobility time) and also the anxiolytic behavior (tendency for discovery in the center and illuminated areas) better even than those of paroxetine and bromazepam (classic drugs) concomitant with those results the extract also showed an important antioxidant capacity. These preliminary results suggest that Petroselinum sativum exhibits anxiolytic and antidepressant potential for use as a complement or independent phytomedicine to treat depression and anxiety.

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“…HCAs also showed antidepressant activity. Ferulic acid is the most studied HCA, which was able to raise the monoamine neurotransmitter levels in the brain [ 180 ] and neutralize the reduction in reward-seeking behavior [ 181 ]. Other cinnamic acids (e.g., 3,4,5-trimethoxycinnamic, caffeic and p -coumaric acids) were also investigated for their potential antidepressant effects (all studies are reviewed in a recent paper by Diniz et al [ 181 ]).…”

Section: Biological Activities and Health Benefits Of Hcas And Thementioning

confidence: 99%

Natural Sources, Pharmacokinetics, Biological Activities and Health Benefits of Hydroxycinnamic Acids and Their Metabolites

2020

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Hydroxycinnamic acids (HCAs) are important natural phenolic compounds present in high concentrations in fruits, vegetables, cereals, coffee, tea and wine. Many health beneficial effects have been acknowledged in food products rich in HCAs; however, food processing, dietary intake, bioaccessibility and pharmacokinetics have a high impact on HCAs to reach the target tissue in order to exert their biological activities. In particular, metabolism is of high importance since HCAs’ metabolites could either lose the activity or be even more potent compared to the parent compounds. In this review, natural sources and pharmacokinetic properties of HCAs and their esters are presented and discussed. The main focus is on their metabolism along with biological activities and health benefits. Special emphasis is given on specific effects of HCAs’ metabolites in comparison with their parent compounds.

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Antidepressant Potential of Cinnamic Acids: Mechanisms of Action and Perspectives in Drug Development

Cited by 23 publications

References 55 publications

Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach

Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach

The Potential of Parsley Polyphenols and Their Antioxidant Capacity to Help in the Treatment of Depression and Anxiety: An In Vivo Subacute Study

Natural Sources, Pharmacokinetics, Biological Activities and Health Benefits of Hydroxycinnamic Acids and Their Metabolites

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