Role Of Ferulic Acid Research Articles

Ferulic Acid reduces amyloid beta mediated neuroinflammation through modulation of Nurr1 expression in microglial cells.

Microglial cells (MGCs) serve as the resident macrophages in the brain and spinal cord, acting as the first line of immune defense against pathological changes. With various phenotypes, they can shift from a homeostatic state to a reactive state or transit from a reactive to a non-inflammatory reactive state (alternative homeostatic). A well-timed transit is crucial in limiting excessive microglial reaction and promoting the healing process. Studies indicate that increased Nurr1 expression promotes anti-neuroinflammatory responses in the brain. In this study, we investigated the possible role of ferulic acid (FA) in facilitating microglia transition due to its anti-inflammatory and Nurr1-inducing effects. MGCs were extracted from the brains of male NMRI mice at postnatal day 2 (P2) and cultured with or without FA and beta-amyloid (Aβ). Real-time qRT-PCR was conducted to measure the expressions of Nurr1, IL-1β, and IL-10 genes. Immunostaining was performed to determine the number of NURR1-positive cells, and the ramification index (RI) of MGCs was calculated using Image J software. Treating MGCs with FA (50 μg/ml) induced Nurr1 and IL-10 expressions, while reducing the level of IL-1β in the absence of Aβ-stress. Further assessments on cells under Aβ-stress showed that FA treatment restored the IL-10 and Nurr1 levels, increased the RI of cells, and the number of NURR1-positive cells. Morphological assessments and measurements of the RI revealed that FA treatment reversed amoeboid and rod-like cells to a ramified state, which is specific morphology for non-inflammatory reactive microglia. To conclude, FA can provide potential alternative homeostatic transition in Aβ-reactive microglia by recruiting the NURR1 dependent anti-inflammatory responses. This makes it a promising therapeutic candidate for suppressing Aβ-induced neuroinflammatory responses in MGCs. Furthermore, given that FA has the ability to increase NURR1 levels in homeostatic microglia, it could be utilized as a preventative medication.

ALDH2C4 regulates cuticle thickness and reduces water loss to promote drought tolerance

In Arabidopsis thaliana, ALDH2C4 encodes coniferaldehyde dehydrogenase, which oxidizes coniferaldehyde to ferulic acid. Drought stress is one of the important abiotic stresses affecting plant growth. However, the role of ferulic acid in drought resistance is unknown. To investigate the contribution of ferulic acid to cuticle composition and drought resistance, we used two Arabidopsis aldh2c4 mutant lines. Compared with wild-type (WT) leaves, ferulic acid contents were significantly lower (by more than 50 %) in mutants. The mutants also had lower amounts of cutin and wax, primarily due to reductions in C18:2 dioic acid and alkanes, respectively. Furthermore, the leaves of the mutant plants exhibited greater rates of water loss and released chlorophyll faster than WT leaves when immersed in 80 % ethanol, indicating a defective cuticle barrier. The growth of aldh2c4 mutants was severely inhibited, and their leaves showed a higher degree of wilting relative to the WT plants under drought conditions. In aldh2c4 complementation lines, the growth inhibition of the mutant plants under drought stress was alleviated. Taken together, our results demonstrate that ferulic acid plays an important role in the composition and structural properties of the cuticle and that a ferulic acid deficiency in the cutin leads to reduced drought tolerance.

Ferulic acid mediates prebiotic responses of cereal-derived arabinoxylans on host health.

Dietary fiber is named as “the 7th nutrient” for humans, which is beneficial to improve intestinal health and prevent metabolic disease of the host. Mechanisms of dietary fiber administration on improved host health are mediated by short chain fatty acids (SCFA), which are reported to activate G protein-coupled receptors (GPR) and suppress activity of histone deacetylase (HDAC) to down-regulate expression of nuclear factor-к-gene binding (NF-кB) signaling. Arabinoxylan is fermented by gut microbiota to produce SCFA and improved microbial community composition, intestinal barrier functions and host health. Interestingly, the latest publications have observed that ferulic acid combined with the arabinose in arabinoxylans from various cereal grains can be released through gut microbial fermentation. Ferulic acid can improve antioxidase activity and decrease reactive oxygen species (ROS) concentration by activating the signaling pathway of Kelch-like ECH-associated protein-1 and nuclear factor E2-related factor-2 (Keap1-Nrf2). However, the role of ferulic acid in cooperation with SCFA produced from microbial fermentation of cereal-derived arabinoxylan to regulate the intestinal health and host metabolisms, has been widely unclear. This review summarizes the potential mechanisms of ferulic acid from microbial fermentation of cereal-derived arabinoxylans on immunological functions and physiological metabolisms of the host. The evidence presented in the review indicates that dietary supplementation with cereal-derived arabinoxylans improves antioxidant capacity of intestinal epithelial cells due to the production of ferulic acid and SCFA from microbial fermentation. Ferulic acid can cooperate with SCFA to regulate intestinal integrity and immunological functions of the host. Peroxisome proliferator activated-receptor γ (PPARγ) may play an important role in integrating ferulic acid and SCFA to regulate host health and metabolism.

Theoretical Study of Radical Inactivation, LOX Inhibition, and Iron Chelation: The Role of Ferulic Acid in Skin Protection against UVA Induced Oxidative Stress.

Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of •OH generation. The resulting FA phenoxyl radical, after the scavenging of a second •OH and keto-enol tautomerization of the intermediate, produces 5-hydroxyferulic acid (5OHFA). Inhibition of the lipoxygenase (LOX) enzyme, one of the enzymes that catalyse free radical production, by FA and 5OHFA were analysed. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with the LOX active site. The exergonicity of chelation reactions of the catalytic Fe2+ ion with FA and 5OHFA indicate the potency of these chelators to prevent the formation of •OH radicals via Fenton-like reactions. The inhibition of the prooxidant LOX enzyme could be more relevant mechanism of skin protection against UVA induced oxidative stress than iron chelation and assumed direct scavenging of ROS.

Naringin inhibits the Zea mays coniferyl aldehyde dehydrogenase: an in silico and in vitro approach

An additional reaction of the plant phenylpropanoid pathway is that catalyzed by coniferyl aldehyde dehydrogenase (HCALDH) to form cytosolic ferulic acid from coniferaldehyde. Because ferulic acid anchors lignin in cell wall polysaccharides and causes cell wall recalcitrance, the HCALDH inhibition could be a prominent target to release fermentable sugars from lignocellulose biomass and improve the saccharification efficiency. Here, we evaluated the role of the flavanone glycoside naringin (NRG), prospected in silico, as a selective inhibitor of the HCALDH of Zea mays (ZmaysHCALDH). A homotetrameric structural model in the absence of ligands was used for evaluations. The stability of the ZmaysHCALDH–NRG complex was checked via molecular dynamics simulation of the apo form (Apo–HCALDH) and that bonded to the inhibitor (NRG–HCALDH), both for the tetrameric form. The conformation bound to NRG varied less in relation to the apo form, and thus could be considered more stable. To obtain kinetic parameters, activities of a partially purified ZmaysHCALDH preparation were determined in vitro using high performance liquid chromatography. In comparison to the NRG-free control, Vmax and Km data suggested a kinetic profile of uncompetitive inhibition with respect to the substrate coniferyl aldehyde. In brief, this combinatorial in silico and in vitro approach suggest that NRG-induced inhibition of ZmaysHCALDH may be an attractive strategy to explore new clues regarding the phenylpropanoid pathway, the role of ferulic acid in the cell wall and, and mainly the digestibility of lignocellulosic biomass for biorefinery purposes.

Effect of Ferulic Acid, a Phenolic Inducer of Fungal Laccase, on 26S Proteasome Activities In Vitro.

The 26S proteasome is an ATP-dependent protease complex (2.5 MDa) that degrades most cellular proteins in Eukaryotes, typically those modified by a polyubiquitin chain. The proteasome-mediated proteolysis regulates a variety of critical cellular processes such as transcriptional control, cell cycle, oncogenesis, apoptosis, protein quality control, and stress response. Previous studies conducted in our laboratory have shown that 26S proteasomes are involved in the regulation of ligninolytic enzymes (such as laccase) in white-rot fungi in response to nutrient starvation, cadmium exposure, and ER stress. Laccases are useful biocatalysts for a wide range of biotechnological applications. The goal of the current study was to determine the effect of ferulic acid (4-hydroxy-3-methoxycinnamic acid), a phenolic compound known to induce some ligninolytic enzymes, on proteasomes isolated from mycelia of the wood-decomposing basidiomycete Trametes versicolor. The peptidase activities of 26S proteasomes were assayed by measuring the hydrolysis of fluorogenic peptide substrates specific for each active site: Suc-LLVY-AMC, Z-GGR-AMC and Z-LLE-AMC for chymotrypsin-like, trypsin-like, and caspase-like site, respectively. Ferulic acid affected all peptidase activities of the 26S fungal proteasomes in a concentration-dependent manner. A possible inhibitory effect of ferulic acid on peptidase activities of the 26S human proteasomes was tested as well. Moreover, the ability of ferulic acid to inhibit (at concentrations known to induce laccase activity in white-rot fungi) the rate of 26S proteasome-catalyzed degradation of a model full-length protein substrate (β-casein) was demonstrated by a fluorescamine assay and by a gel-electrophoretic analysis. Our findings provide new insights into the role of ferulic acid in lignin-degrading fungi. However, the detailed molecular mechanisms involved remain to be elucidated by future studies.

The role of ferulic acid in the amelioration of kidney changes of rats exposed to electromagnetic radiation

The role of ferulic acid in the amelioration of kidney changes of rats exposed to electromagnetic radiation

Ferulic Acid Orchestrates Anti-Oxidative Properties of Danggui Buxue Tang, an Ancient Herbal Decoction: Elucidation by Chemical Knock-Out Approach.

Ferulic acid, a phenolic acid derived mainly from a Chinese herb Angelica Sinensis Radix (ASR), was reported to reduce the formation of free radicals. Danggui Buxue Tang (DBT), a herbal decoction composing of Astragali Radix (AR) and ASR, has been utilized for more than 800 years in China having known anti-oxidative property. Ferulic acid is a major active ingredient in DBT; however, the role of ferulic acid within the herbal mixture has not been resolved. In order to elucidate the function of ferulic acid within this herbal decoction, a ferulic acid-depleted herbal decoction was created and named as DBTΔfa. The anti-oxidative properties of chemically modified DBT decoction were systemically compared in cultured H9C2 rat cardiomyoblast cell line. The application of DBT and DBTΔfa into the cultures showed functions in (i) decreasing the reactive oxygen species (ROS) formation, detected by laser confocal; (ii) increasing of the activation of Akt; (iii) increasing the transcriptional activity of anti-oxidant response element (ARE); and (iv) increasing the expressions of anti-oxidant enzymes, i.e. NQO1 and GCLM. In all scenario, the aforementioned anti-oxidative properties of DBTΔfa in H9C2 cells were significantly reduced, as compared to authentic DBT. Thus, ferulic acid could be an indispensable chemical in DBT to orchestrate multi-components of DBT as to achieve maximal anti-oxidative functions.

The role of ferulic acid and arabinoxylan in inducing premature yeast flocculation

Premature yeast flocculation (PYF) is a universal phenomenon and has caused serious problems in the brewing industry. For brewing quality control, it is of great value to investigate the PYF factors that induce this destructive phenomenon. In the present study, two barley malts (PYF+ and PYF−), made from the same barley cultivar by one maltster in China, were selected for PYF factor investigations. The results showed that considerably higher amounts of the bound ferulic acid (FA), rather than arabinoxylan (AX), existed in the PYF+ wort compared with the PYF− wort. To better understand the role of these polysaccharides in PYF+ and PYF− wort, they were fractional precipitated with graded ethanol concentrations. The AX and FA contents in each fraction, as well as the molecular weight profiles and monosaccharide composition, were determined. Furthermore, the PYF−inducing activities of each fraction were measured using a small-scale fermentation. It was found that the 40% ethanol-precipitated fraction of both the PYF+ and PYF− wort, and the 60% fraction from the PYF+ wort, could induce the severe PYF phenomenon when added to the PYF− wort. These fractions were proposed to contain PYF factors of suitable molecular weight and a sufficient amount of the polysaccharides. In addition, it was found that the bound FA in arabinoxylan behaved as an important PYF factor in barley malt. The results of this work may contribute to the further study of the PYF mechanism. Copyright © 2015 The Institute of Brewing & Distilling

Ferulic Acid Enhances the Chemical and Biological Properties of Astragali Radix: A Stimulator for Danggui Buxue Tang, An Ancient Chinese Herbal Decoction

Danggui buxue tang, an ancient formula composed of astragali radix and Angelicae sinensis radix, has been used for treating menopausal irregularity in women for more than 800 years in China. In danggui buxue tang, the complete functions of astragali radix require the assistance of Angelicae sinensis radix, and both herbs have to work harmoniously in order to achieve the maximal therapeutic purposes. In order to analyze the relationship of the two herbs, the role of ferulic acid, a major chemical within Angelicae sinensis radix, in chemical and biological properties of astragali radix was determined. Using ferulic acid in the extraction of astragali radix, the amounts of astragaloside IV, calycosin, and formononetin were increased in the final extract; however, the astragali radix polysaccharide showed a minor increase. The chemical-enriched astragali radix extract showed robust induction in osteogenic and estrogenic activities in cultured osteosarcoma MG-63 and breast MCF-7 cells. However, ferulic acid itself did not show such biological responses. The current results strongly suggest that Angelicae sinensis radix-derived ferulic acid is a positive regulator for danggui buxue tang, which enhanced the solubilities of active ingredients derived from astragali radix, and which therefore increased the biological efficacies of danggui buxue tang.

Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 mL/kg body weight of 50% glycerol, glycerol + ferulic acid at the dose of 5, 10, 15, 20 and 25 mg/kg body weight. After 24 h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.

What can feruloyl esterases do for us?

The role of feruloyl esterases in plant wall development, in gut health, and in the breakdown of plant biomass for the production of bioactive phytochemicals and biofuel is covered in this review. These enzymes have potential roles in stomatal cell function and the phenolic substitutions and cross-linkages between plant cell wall components. As more plant genomes are sequenced, the role of ferulic acid and feruloyl esterases in planta may be better understood. In human and ruminal digestion, these enzymes are important to de-esterify dietary fibre, releasing hydroxycinnamates and derivatives which have been shown to have positive health effects, such as antioxidant, anti-inflammatory and anti-microbial activities. They are also involved in colonic fermentation where their extracellular and intracellular activities in the microbiota improve the breakdown of polysaccharides and increase microbial production of short chain fatty acids. Their specificity can also be employed to synthesize bioactive compounds for cosmetic and health applications. The enzymatic disassembly of cereal straws is greatly enhanced when feruloyl esterase activity is present, although the substrate specificity of the esterase appears to have some bearing on its optimal application. The involvement of feruloyl esterases in the improved enzymatic and microbial saccharification of cereal-derived material demonstrates a high importance for these enzymes in animal feed preparation and bioalcohol production.

Elaboration of the 6,7,8 Oxygenation Pattern in Simple Coumarins: Biosynthesis of Puberulin in Agathosma puberula Fourc

Abstract Umbelliferone and scopoletin are well utilized as precursors of puberulin, a 7-O-prenyl ether of isofraxidin elaborated by Agathosm a puberula Fourc. (Rutaceae). As ferulic, sinapic, and caffeic acids were all more poorly utilized than 4′-hydroxycinnamic (p-coumaric) acid, the partial biosynthetic route: 4′-hydroxycinnamic acid →→ um belliferone → aesculetin → scopoletin →→ puberulin is suggested as the major pathway. Prenylether formation apparently occurs at or beyond the scopoletin stage. The implication that ferulic acid does not participate in the formation of scopoletin from 4′-hydroxycinnamic acid is at variance with the known role of ferulic acid as a scopoletin precursor in tobacco.