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Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phenolic compound present in several plants with claimed beneficial effects in prevention and treatment of disorders linked to oxidative stress and inflammation.IC50 value:Target: 5-HT ReceptorIn vitro: In the present study we have showed that pre-treatment with Ferulic Acid (FA) reduces NO accumulation in the culture medium of LPS-induced macrophage cells. Moreover, real-time experiments have revealed that FA has an inhibitory effect at the transcriptional level on the expression of some inflammatory mediators such as IL-6, TNF-α and iNOS and an activation effect on the expression of some antioxidant molecules such as Metallothioneins (MT-1, MT-2). Importantly, we have found that FA reduced the translocation of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor-κB (NF-κB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibited IL-6 and NF-κB promoter activity in a luciferase assay [1]. FA treatment significantly, although not completely, protected the cells against lead acetate-induced neurite outgrowth inhibition. The effects of FA could be blocked by PD98059, zinc protoporphyrin (Zn-PP), and Nrf2 shRNA. In addition, FA induced heme oxygenase 1 (HO-1) gene expression, enhanced antioxidant response element (ARE) promoter activity, promoted ERK1/2 phosphorylation, and Nrf2 translocation in PC12 cells exposed to lead acetate. ERK1/2 locate upstream of Nrf2 and regulate Nrf2-dependent HO-1 expression in antioxidative effects of FA [2].In vivo: We aimed to verify the possible antidepressant-like effect of acute oral administration of Ferulic acid produced an antidepressant-like effect in the FST and TST (0.01-10 mg/kg, p.o.), without ccompanying changes in ambulation. The pretreatment of mice with WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor ntagonist) or ketanserin (5 mg/kg, i.p., a 5-HT2A receptor ntagonist) was able to reverse the anti-immobility effect of ferulicacid (0.01 mg/kg, p.o.) in the TST. The combination of fluoxetine (5 mg/kg, p.o.), paroxetine (0.1 mg/kg, p.o.) or sertraline (1 mg/kg, p.o.) with a sub-effective dose of ferulic acid (0.001 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing hyperlocomotion in the open-field test. ferulic acid in the forced swimming test (FST) and tail suspension test (TST) in mice [3].

[1]. Ana Lúcia B. Zeni, et al. Ferulic acid exerts antidepressant-like effect in the tail suspension test in mice: Evidence for the involvement of the serotonergic system. European Journal of Pharmacology 679 (2012) 68-74 [2]. Lampiasi N, et al. The molecular events behind ferulic acid mediated modulation of IL-6 expression in LPS-activated Raw 264.7 cells. Immunobiology. 2015 Nov 10. [3]. Yu CL, et al. Ferulic Acid Protects Against Lead Acetate-Induced Inhibition of Neurite Outgrowth by Upregulating HO-1 in PC12 Cells: Involvement of ERK1/2-Nrf2 Pathway. Mol Neurobiol. 2015 Nov 26.

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