Trans-Ferulic acid

Colloids Surf B Biointerfaces. 2013 Sep 1;109:273-9.

Trans-ferulic acid-based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes.[Pubmed: 23668982]

METHODS AND RESULTS:
In this study, stearic acid- and stearyl ferulate-based solid lipid nanoparticles containing Trans-Ferulic acid (SLN-FA and SLN-SF-FA, respectively), were prepared and characterized for loading efficiency, size and shape. In addition, by using rat brain microsomes, we evaluated in vitro the antioxidant activity of these formulations against three well known initiators of lipid peroxidation, such as AAPH, NADPH/ADP-Fe(3+) and SIN-1 which in turn generate the peroxyl and perferryl radicals as well as peroxynitrite, respectively. Commercially available FA and its ethyl ester (FAEE) were used as comparators. Both SLN-FA and SLN-SF-FA dose-dependently reduced lipid peroxidation induced by the three oxidants. Interestingly, SLN-SF-FA displayed greater efficacy (EC50) and potency (maximal activity) against AAPH- and NADPH/ADP-Fe(3+)-induced lipid peroxidation.
CONCLUSIONS:
Our results support the idea that this new formulations could facilitate the uptake of FA by the cells because of their lipophilic structure, thus increasing FA bioavailability. Furthermore, stearyl ferulate-based nanoparticles could prevent the degradation of FA entrapped on their structure, making FA almost entirely available to explicate its antioxidant power once released.

Chem Pharm Bull (Tokyo). 2010 Jan;58(1):103-5.

L-lysine pro-prodrug containing trans-ferulic acid for 5-amino salicylic acid colon delivery: synthesis, characterization and in vitro antioxidant activity evaluation.[Pubmed: 20045975]

In the present work, we report the synthesis of a new 5-amino salicylic acid (5-ASA) pro-prodrug, useful in Crohn disease treatment, and the evaluation of its antioxidant activity.
METHODS AND RESULTS:
Using as pharmacological carrier L-lysine amino acid and taking advantage of its intrinsic chemical reactivity, due to the presence of two amino groups, placed on the chiral center and in epsilon-position, we inserted Trans-Ferulic acid in epsilon-position, through amidation reaction, esterified with methanol the carboxylic group and, finally, submitted the free amino group to diazotation with 5-ASA, principal drug for inflammatory bowel diseases (IBD) care. All intermediates of synthesis and the final product (derivative A) were characterized with usual spectroscopic techniques, as FT-IR, GC/MS and (1)H-MNR. Finally, the derivative A antioxidant activity in inhibiting the lipid peroxidation, in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals, 2,2'-azobis (2-amidinopropane) (AAPH) and tert-butyl hydroperoxide (tert-BOOH), was evaluated.
CONCLUSIONS:
Our pro-prodrug could be successfully applied in pharmaceutical field both as prodrug of 5-ASA than as carrier of Trans-Ferulic acid.

Chin Med . 2016 Oct 1;11:45.

Inhibitory effect of trans-ferulic acid on proliferation and migration of human lung cancer cells accompanied with increased endogenous reactive oxygen species and β-catenin instability[Pubmed: 27733866]

Abstract Background: Trans-ferulic (FA) acid exhibits antioxidant effects in vitro. However, the underlying mechanism of trans-FA activity in cellular physiology, especially cancer physiology, remains largely unknown. This study investigated the cellular physiological effects of trans-FA on the H1299 human lung cancer cell line. Methods: The 2,2-diphenyl-1-picrylhydrazyl assay was used to determine free radical scavenging capability. Assessment of intracellular reactive oxygen species (ROS) was evaluated using oxidized 2',7'-dichlorofluorescin diacetate and dihydroethidium staining. Trypan blue exclusion, colony formation, and anchorage-independent growth assays were used to determine cellular proliferation. Annexin V staining assay was used to assess cellular apoptosis by flow cytometry. Wound healing and Boyden's well assays were used to detect the migration and invasion of cells. Gelatin zymography was used to detect matrix metalloproteinase (MMP-2 and MMP-9) activity. Western blotting was used to detect expression levels of various signaling pathway proteins. Results: DPPH assay results indicated that trans-FA exerted potent antioxidant effects. However, trans-FA increased intracellular ROS levels, including hydrogen peroxide and superoxide anion, in H1299 cells. Trans-FA treatment inhibited cellular proliferation and induced moderate apoptotic cell death at the highest concentration used (0.6 mM). Furthermore, trans-FA moderately inhibited the migration of H1299 cells at the concentrations of 0.3 and 0.6 mM and attenuated MMP-2 and MMP-9 activity. Trans-FA caused the phosphorylation of β-catenin, resulting in proteasomal degradation of β-catenin. Conversely, trans-FA treatment increased the expression of pro-apoptotic factor Bax and decreased the expression of pro-survival factor survivin. Conclusion: Various concentrations (0.06-0.6 mM) of trans-FA exert both anti-proliferation and anti-migration effects in the human lung cancer cell line H1299.

Phytomedicine. 2008 Nov;15(11):951-8.

The effect of trans-ferulic acid and gamma-oryzanol on ethanol-induced liver injury in C57BL mouse[Pubmed: 18424018]

The effects of the oral administration of Trans-Ferulic acid and gamma-oryzanol (mixture of steryl ferulates) with ethanol (5.0 g per kg) for 30 days to c57BL mice on ethanol-induced liver injury were investigated.
METHODS AND RESULTS:
Preventions of ethanol-induced liver injury by Trans-Ferulic acid and gamma-oryzanol were reflected by markedly decreased serum activities of plasma aspartate aminotransferase, alanine aminotransferase and significant decreases in hepatic lipid hydroperoxide and TBARS levels. Furthermore, the Trans-Ferulic acid- and gamma-oryzanol-treated mice recovered ethanol-induced decrease in hepatic glutathione level together with enhancing superoxide dismutase activity.
CONCLUSIONS:
These results demonstrate that both Trans-Ferulic acid and gamma-oryzanol exert a protective action on liver injury induced by chronic ethanol ingestion.

J Funct Biomater. 2014 Jul 24;5(3):99-110.

A new pro-prodrug aminoacid-based for trans-ferulic Acid and silybin intestinal release.[Pubmed: 25062426]

The aim of this work was the preparation and characterization of a pro-prodrug able to simultaneously transport silybin, a drug possessing various pharmacological effects, and Trans-Ferulic acid, a known antioxidant.
METHODS AND RESULTS:
More specifically, l-phenylalanine-N-(4-hydroxy-3-methoxy-phenyl) prop-2-en-O-(2R,3R)-3,5,7-trihydroxy-2-((2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-benzo-(1,4)-dioxin-6-yl)croman-4-one was synthesized by using the aminoacid l-phenylalanine (l-Phe) as carrier. Indeed, l-Phe is characterized by an intrinsic chemical reactivity due to the presence of an amino group, placed on the chiral center, and of a carboxylic group. The synthesis has been characterized first by adding silybin by means of carboxylic group and then, with the aim to confer antioxidant properties to this new carrier, by linking Trans-Ferulic acid to l-Phe via amino group. The so obtained derivative was then characterized by FT-IR, and 1H-NMR spectroscopies. Furthermore, its ability to inhibit lipid peroxidation induced by tert-butyl hydroperoxide in rat liver microsomes, was evaluated. The 1,1-diphenyl-2-picrylhydrazyl radical-scavenging effect, was also assessed. The release of silybin and Trans-Ferulic acid was determined in simulated gastric and intestinal fluids over the time. The results showed that the covalent bond between both (i) silybin; or (ii) Trans-Ferulic acid and the amino acid was degraded by enzymatic reactions. In addition, the pro-prodrug, showed strong antioxidant and scavenger activities.
CONCLUSIONS:
Due to these properties, this new pro-prodrug could be applied for the treatment of intestinal pathologies and it might improve the therapeutic potential of silybin which is strongly limited by its low solubility.