Simultaneous suppression of lignin, tricin and wall-bound phenolic biosynthesis via the expression of monolignol 4-O-methyltransferases in rice.

Grass lignocelluloses feature complex compositions and structures. In addition to the presence of conventional lignin units from monolignols, acylated monolignols and flavonoid tricin also incorporate into lignin polymer; moreover, hydroxycinnamates, particularly ferulate, cross-link arabinoxylan chains with each other and/or with lignin polymers. These structural complexities make grass lignocellulosics difficult to optimize for effective agro-industrial applications. In the present study, we assess the applications of two engineered monolignol 4-O-methyltransferases (MOMTs) in modifying rice lignocellulosic properties. Two MOMTs confer regiospecific para-methylation of monolignols but with different catalytic preferences. The expression of MOMTs in rice resulted in differential but drastic suppression of lignin deposition, showing more than 50% decrease in guaiacyl lignin and up to an 90% reduction in syringyl lignin in transgenic lines. Moreover, the levels of arabinoxylan-bound ferulate were reduced by up to 50%, and the levels of tricin in lignin fraction were also substantially reduced. Concomitantly, up to 11 µmol/g of the methanol-extractable 4-O-methylated ferulic acid and 5-7 µmol/g 4-O-methylated sinapic acid were accumulated in MOMT transgenic lines. Both MOMTs in vitro displayed discernible substrate promiscuity towards a range of phenolics in addition to the dominant substrate monolignols, which partially explains their broad effects on grass phenolic biosynthesis. The cell wall structural and compositional changes resulted in up to 30% increase in saccharification yield of the de-starched rice straw biomass after diluted acid-pretreatment. These results demonstrate an effective strategy to tailor complex grass cell walls to generate improved cellulosic feedstocks for the fermentable sugar-based production of biofuel and bio-chemicals.

Engineering a coenzyme-independent dioxygenase for one-step production of vanillin from ferulic acid.

Vanillin is one of the world's most important flavor and fragrance compounds used in foods and cosmetics. In plants, vanillin is reportedly biosynthesized from ferulic acid via the hydratase/lyase-type enzyme VpVAN. However, in biotechnological and biocatalytic applications, the use of VpVAN limits the production of vanillin. Although microbial enzymes are helpful as substitutes for plant enzymes, synthesizing vanillin from ferulic acid in one step using microbial enzymes remains a challenge. Here, we developed a single enzyme that catalyzes vanillin production from ferulic acid in a coenzyme-independent manner via the rational design of a microbial dioxygenase in the carotenoid cleavage oxygenase family using computational simulations. This enzyme acquired catalytic activity toward ferulic acid by introducing mutations into the active center to increase its affinity for ferulic acid. We found that the single enzyme can catalyze not only the production of vanillin from ferulic acid but also the synthesis of other aldehydes from p-coumaric acid, sinapinic acid, and coniferyl alcohol. These results indicate that the approach used in this study can greatly expand the range of substrates available for the dioxygenase family of enzymes. The engineered enzyme enables efficient production of vanillin and other value-added aldehydes from renewable lignin-derived compounds. IMPORTANCE: The final step of vanillin biosynthesis in plants is reportedly catalyzed by the enzyme VpVAN. Prior to our study, VpVAN was the only reported enzyme that directly converts ferulic acid to vanillin. However, as many characteristics of VpVAN remain unknown, this enzyme is not yet suitable for biocatalytic applications. We show that an enzyme that converts ferulic acid to vanillin in one step could be constructed by modifying a microbial dioxygenase-type enzyme. The engineered enzyme is of biotechnological importance as a tool for the production of vanillin and related compounds via biocatalytic processes and metabolic engineering. The results of this study may also provide useful insights for understanding vanillin biosynthesis in plants.

Ferulic acid ameliorates concanavalin A-induced hepatic fibrosis in mice via suppressing TGF-ß/smad signaling.

BACKGROUND AND AIM: Hepatic fibrosis, one of the main reasons for death globally, is a serious complication of chronic liver disorders. However, the available therapies for liver fibrosis are limited, ineffective, and often associated with adverse events. Hence, seeking for a novel, effective therapy is warranted. Our objective was to investigate the potential efficacy of ferulic acid (FA), a phenolic phytochemical, at different doses in hindering the progress of concanavalin A (Con A)-induced hepatic fibrosis and explore the involved mechanisms. METHODS: Thirty-six mice were assorted into 6 groups (n = 6): Group I (control); group II received FA (20 mg/kg/day orally for 4 weeks); group III received Con A (6 mg/kg/week/i.v.) for 4 weeks; groups IV, V, and VI received Con A and were offered FA at 5, 10, and 20 mg/kg/day, respectively. RESULTS: The data showed the palliative effect of FA against Con A-induced fibrosis in a dose-dependent manner. This was obvious from the recovery of liver markers and hepatic architecture with the regression of fibrosis in FA-treated mice. FA abolished Con A-mediated oxidative insults and promoted the antioxidant enzyme activities, which run through the Nrf2/HO-1 signaling. Additionally, FA suppressed Con A-induced increase in NF-kB and IL-ß levels, and TNF-α immune-expression. The anti-fibrotic effect of FA was evident from the drop in TGF-ß, smad3 levels, α-SMA expression, and hydroxyproline content. CONCLUSION: FA attenuated Con A-induced liver fibrosis through stimulating Nrf2 signaling, suppressing NF-kB, and inhibiting the TGF-ß/smad3 signaling pathway. Thus FA can be considered as a promising therapy for combating liver fibrosis.

Ferulic acid protects against gamma-radiation induced liver injury via regulating JAK/STAT/Nrf2 pathways.

This study aims to evaluate the effect and underlying mechanism of ferulic acid (FA) in alleviating the acute liver injury by ionizing radiation (IR) in vivo. Rats were divided into 4groups (Groups: control, 6Gy irradiated (IRR), FA (50 mg/kg) and FA + IRR). The results showed that FA can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, FA prevented IR-induced liver fibrosis and blocked the JAK/STAT signaling pathway to effectively inhibit the hepatic inflammatory response; and inhibited IR-induced oxidative stress (OS) by upregulating the Nrf2 signaling pathway and promoting the synthesis of several antioxidants. Moreover, FA inhibited ferroptosis in the liver by stimulating the expression of GPX4 and SLC7A11. FA reduced lipid peroxidation by downregulation of the reactive oxygen species (ROS) production and iron aggregation, thus inhibiting ferroptosis and alleviating IR-induced liver injury. In conclusion, the current study suggests the potential complex mechanisms underlying the mitigating impact of FA in IR-induced ferroptotic liver damage.

Sirtuin 1 in osteoarthritis: Perspectives on regulating glucose metabolism.

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments，alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.

Ferulic acid alleviates avermectin induced renal injury in carp by inhibiting inflammation, oxidative stress and apoptosis.

Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 µg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-ß1 and il-10, while significantly down-regulated the gene expression levels of tnf-α, il-6 and il-1ß. These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.

Protective effect of feed additive ferulic acid on respiratory depression and oxidation imbalance of carp induced by pesticide difenoconazole via ROS/NF-κB/NLRP3 axis.

Difenoconazole (DFZ), classified as a "low-toxicity pesticide," has seen widespread application in recent years. Nevertheless, the non-target toxicity of the substance, particularly towards aquatic creatures, has generated considerable apprehension. The anti-inflammatory and antioxidant effects of Ferulic Acid (FA) have attracted considerable study in this particular setting. This study established a chronic exposure model to DFZ and investigated the protective effects of FA on chronic respiratory inhibition leading to gill damage in freshwater carp. Histological analyses via HE staining indicated that FA effectively alleviated gill tissue damage induced by chronic DFZ exposure. The qRT-PCR results showed that the addition of FA reduced the expression of IL-1ß, IL-6 and TNF-α while boosting the expression of IL-10 and TGF-ß1. Biochemical analyses and DHE staining revealed that FA reduced MDA levels and increased CAT and GSH activities, along with T-AOC, decreased ROS accumulation in response to chronic DFZ exposure. The results obtained from Western blotting analysis demonstrated that the addition of FA effectively suppressed the activation of the NF-κB signalling pathway and the NLRP3 inflammasome pathway in the gills subjected to prolonged exposure to DFZ. In summary, FA ameliorated gill tissue inflammation and blocked ROS accumulation in carp exposed to chronic DFZ, mitigating tissue inflammation and restoring redox homeostasis through the NF-κB-NLRP3 signaling pathway. Hence, the application of FA has been found to be efficacious for improving respiratory inhibition and mitigating gill tissue inflammation and oxidative stress resulting from DFZ pollution in aquatic habitats.

Photophysical Properties of Sinapic Acid and Ferulic Acid and Their Binding Mechanism with Caffeine.

Sinapic acid (SA) and ferulic acid (FA) are bioactive compounds used in the food, pharmaceutical, and cosmetic industries due to their antioxidant properties. In this work, we studied the photophysical properties of SA and FA in different solvents and concentrations and their interactions with caffeine (CF), using ultraviolet-visible (UV-Vis), fluorescence spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The findings show that the quantum yield, fluorescence lifetime, radiative decay rates, and non-radiative decay rates of SA and FA are influenced by the concentrations and solvent polarity. The interaction between SA and FA with CF was also studied using UV-Vis and fluorescence spectroscopy. The results indicate that the CF quenched the fluorescence intensity of SA and FA by static quenching due to the formation of a non-fluorescent complex. The van't Hoff equation suggests that the van der Waals forces and hydrogen bonds force were responsible for the interaction between SA and CF, as indicated by a negative change in enthalpy ( Δ H o  < 0) and a negative change in entropy ( Δ S o  < 0). On the other hand, the interaction between FA and CF was primarily controlled by electrostatic force, as indicated by a negative change in enthalpy ( Δ H o < 0) and a positive change in entropy ( Δ S o > 0). The negative change in Gibbs free energy ( Δ G o ) indicates that both compounds underwent a spontaneous binding process.

Diet-gut microbiome interaction and ferulic acid bioavailability: implications on neurodegenerative disorders.

PURPOSE OF THE REVIEW: Ferulic acid (FA), which occurs naturally as the feruloylated sugar ester in grains, fruits, and vegetables, is critical for combating oxidative stress and alleviating neurodegenerative diseases resulting from free radical-generated protein aggregates in brain cells. However, FA cannot be absorbed in conjugated form. Therefore, strategies to improve the bioavailability of FA are gaining more importance. Ferulic acid esterases (FAE) of the gut microbiota are critical enzymes that facilitate FA release from feruloylated sugar ester conjugates and influence systemic health. This review provides insight into a nutrition-based approach to preventing neurodegenerative disorders such as Alzheimer's and Parkinson's by altering the diversity of FAE-producing gut microbiota. RECENT FINDINGS: The human gut is a niche for a highly dense microbial population. Nutrient components and the quality of food shape the gut microbiota. Microbiota-diet-host interaction primarily involves an array of enzymes that hydrolyse complex polysaccharides and release covalently attached moieties, thereby increasing their bio-accessibility. Moreover, genes encoding polysaccharide degrading enzymes are substrate inducible, giving selective microorganisms a competitive advantage in scavenging nutrients. Nutraceutical therapy using specific food components holds promise as a prophylactic agent and as an adjunctive treatment strategy in neurotherapeutics, as it results in upregulation of polysaccharide utilisation loci containing fae genes in the gut microbiota, thereby increasing the release of FA and other antioxidant molecules and combat neurodegenerative processes.

Recovery of green phenolic compounds from lignin-based source: Role of ferulic acid esterase towards waste valorization and bioeconomic perspectives.

The production of chemicals/products so far relies on fossil-based resources with the creation of several environmental problems at the global level. In this situation, a sustainable and circular economy model is necessitated to mitigate global environmental issues. Production of biowaste from various processing industries also creates environmental issues which would be valorized for the production of industrially important reactive and bioactive compounds. Lignin acts as a vital part in biowaste composition which can be converted into a wide range of phenolic compounds. The phenolic compounds have attracted much attention, owing to their influence on diverse not only organoleptic parameters, such as taste or color, but also active agents for active packaging systems. Crop residues of varied groups, which are an affluent source of lignocellulosic biomass could serve as a renewable resource for the biosynthesis of ferulic acid (FA). FA is obtained by the FA esterase enzyme action, and it can be further converted into various tail end phenolic flavor green compounds like vanillin, vanillic acid and hydroxycinnamic acid. Lignin being renewable in nature, processing and management of biowastes towards sustainability is the need as far as the global industrial point is concerned. This review explores all the approaches for conversion of lignin into value-added phenolic compounds that could be included to packaging applications. These valorized products can exhibit the antioxidant, antimicrobial, cardioprotective, anti-inflammatory and anticancer properties, and due to these features can emerge to incorporate them into production of functional foods and be utilization of them at active food packaging application. These approaches would be an important step for utilization of the recovered bioactive compounds at the nutraceutical and food industrial sectors.

Metabolomic analysis of hydroxycinnamic acid inhibition on Saccharomyces cerevisiae.

Ferulic acid (FA) and p-coumaric acid (p-CA) are hydroxycinnamic acid inhibitors that are mainly produced during the pretreatment of lignocellulose. To date, the inhibitory mechanism of hydroxycinnamic acid compounds on Saccharomyces cerevisiae has not been fully elucidated. In this study, liquid chromatography-mass spectrometry (LC-MS) and scanning electron microscopy (SEM) were used to investigate the changes in S. cerevisiae cells treated with FA and p-CA. In this experiment, the control group was denoted as group CK, the FA-treated group was denoted as group F, and the p-CA-treated group was denoted as group P. One hundred different metabolites in group F and group CK and 92 different metabolites in group P and group CK were selected and introduced to metaboanalyst, respectively. A total of 38 metabolic pathways were enriched in S. cerevisiae under FA stress, and 27 metabolic pathways were enriched in S. cerevisiae under p-CA stress as identified through Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis. The differential metabolites involved included S-adenosine methionine, L-arginine, and cysteine, which were significantly downregulated, and acetyl-CoA, L-glutamic acid, and L-threonine, which were significantly upregulated. Analysis of differential metabolic pathways showed that the differentially expressed metabolites were mainly related to amino acid metabolism, nucleotide metabolism, fatty acid degradation, and the tricarboxylic acid cycle (TCA). Under the stress of FA and p-CA, the metabolism of some amino acids was blocked, which disturbed the redox balance in the cells and destroyed the synthesis of most proteins, which was the main reason for the inhibition of yeast cell growth. This study provided a strong scientific reference to improve the durability of S. cerevisiae against hydroxycinnamic acid inhibitors. KEY POINTS: • Morphological changes of S. cerevisiae cells under inhibitors stress were observed. • Changes of the metabolites in S. cerevisiae cells were explored by metabolomics. • One of the inhibitory effects on yeast is due to changes in the metabolic network.

Virulent-MDR-ESBL E. coli and Klebsiella pneumoniae report from North Sinai calves diarrhea and in vitro antimicrobial by Moringa oleifera.

The health of calves has a significant impact on the production of cows and livestock. Some desert plants have pharmacological importance, as they can be used to reduce antibiotic resistance. Our hypothesis is designed to detect Virulent- Multidrug-Resistant and Extended- spectrum Beta- lactamase Enterobacteriaceae (Virulent-MDR-ESBL Enterobacteriaceae and to determine whether Moringa oleifera has antibacterial activity against the detected isolates. A total of 39 Enterobacteriaceae isolates from 28 diarrheic samples were collected from calves aged between 20 days and 20 months from 3 different flocks in North Sinai, Sahl-Eltina region, Egypt. E.coli 46% (18/39), O157 13% (5/39), Klebsiella pneumoniae 41% (16/39). MDR members accounted for 87%, while ESBL isolates accounted for 43%. The antibacterial activity is represented by microdilution. Minimum inhibition concentration (MIC) for the methanol extract of Moringa oleifera ranged from 2.5,5,10, and 25mg/ ml among E.coli isolates, and O157 was susceptible to (2.5mg/ ml), Klebsiella pneumoniae isolates were susceptible to (5-50mg/ ml). Analysis of the methanol extract revealed that ferulic acid was the dominant phenolic compound with a concentration of 29,832 parts per million (ppm). In silico docking study expected the active site of ferulic acid to act on the tyrosine bacterial enzyme through Pi-alkyl, Pi-anion, Carbon hydrogen bonds, and extra ionic attractive interactions with copper ions which can stabilize ferulic acid inside the targeted pocket Diverse virulent gene profiles were observed in E. coli. The Shiga toxin-producing Escherichia coli (STEC) was reported in 83% of the isolated E. coli, while the DNA gyrase (gyrA) was harbored in 100% of Klebsiella pneumoniae isolates. Various profiles of antibiotic resistance genes for both E. coli and Klebsiella pneumoniae isolates were distinguished. blaTEM genes were detected in 99% of E. coli and 100% of Klebsiella pneumoniae. Sequence analysis for E. coli strain DRC-North Sinai-Eg was placed in accession numbers (OP955786) for the Shiga toxin 2 gene (Stx2A), (OP997748) and (OP997749) for the Adhesion to host cell gene (Eae). For the hemolysine gene (hylA), the accession number was (OP946183). Klebsiella pneumoniae strain DRC-North Sinai-Eg was placed in (OP946180) for (gyrA). This study has proven the broad range of Moringa oliefera's antibacterial effects in vitro against the virulent-MDR- ESBL E. coli and Klebsiella pneumoniae isolated from North Sinai calves diarrhea. These are congruent with the disability effect on bacterial tyrosinase enzyme through docking study therefore, we recommend the usage of this desert plant as a prospective feed additive, we endorse this as an antibacterial new insight natural source and for the medication of considered pathogens with zoonotic impacts.

Recycling of deep eutectic solvent in the extraction of ferulic acid from oil palm empty fruit bunch.

The study explored ferulic acid extraction from palm empty fruit bunch (EFB) fiber using deep eutectic solvent (DES) of chlorine chloride-acetic acid as the extraction medium and the way to recover and recycle the DES thereafter. Antisolvent was added to selectively precipitate the ferulic acid, which was recovered by filtration thereafter. Recycling the DES without further purification led to increased ferulic acid yield with each subsequent extraction, likely due to retained ferulic acid. The retained ferulic acid and other impurities could be removed by precipitation brought upon by the addition of a second antisolvent. 1H nuclear magnetic resonance revealed that there was no excess ferulic acid in the recycled DES-treated with two types of antisolvents (ethanol and water). The yield of ferulic acid increased from 0.1367-0.1856 g/g when treated with only one antisolvent to 0.1368-0.2897 g/g with two antisolvent treatments. Oil droplets were also observed in the DES upon the addition of antisolvent 2, with recovered oil ranging from 0.6% to 3%. The study emphasized the significance of using DES as an extraction medium for ferulic acid from oil palm EFB fiber and the method to recycle the DES for subsequent processes.

Effects of apigenin and trans-ferulic acid on microscopic and oxidative stress parameters in the semen of water buffalo bulls during cryopreservation.

Cryopreservation involves exposing sperm to stressful conditions that affect cell viability. The high quality of the Azerbaijani water buffalo's by-products, such as buffalo milk, makes it a species of significant importance. Our focus is on protecting its genetic resources by preserving its sperm, as their numbers will decrease in the coming years and they are at risk of extinction. This study's goal was to ascertain how apigenin (A) and trans-ferulic acid (t-FA) affected the semen quality of Azari water buffalo bulls under cryopreservation. Pooled buffalo sperm (n = 35 ejaculations) were diluted in a Tris-based diluent also containing varying amounts of apigenin (0.2, 0.4, 0.6, and 0.8 mM) and trans-ferulic acid (2.5, 5, 10 and 20 mM). Following a freeze-thaw procedure, samples were assayed for total antioxidant capacity (TAC), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione activity (GSH), glutathione peroxidase (GPx), progressive motility and total motility, motility properties, plasma membrane functionality, and viability. Sixty days after insemination, the rectal examination was performed on 38 buffaloes that had undergone sexual breeding to confirm pregnancy. The results of the study show that the addition of A-0.2, A-0.4, and t-FA-10 to buffalo semen increases the percentage of intact plasma membrane, motility, and sperm viability, as well as the levels of GSH, GPx, CAT. and TAC. In addition, there is a decrease in MDA and DNA damage after cryopreservation. Furthermore, the results show that 0.4 mM apigenin significantly increases conception rates compared to the control group. The base extender of Tris supplemented with A (0.4 and 0.2 mM) and t-FA (10 mM) improves the antioxidant indices of both frozen and thawed buffalo sperm, which in turn improves post-thawing sperm quality and in vivo fertility improves buffalo sperm.

Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms.

Ferulic acid (FA) is a naturally occurring phenolic compound commonly found in the plant Ferula communis. This study aims to investigate the hepatoprotective effect of FA and its derivatives (methyl ferulic acid and trans-ferulic acid) against oxidative stress and inflammation-related hepatotoxicity due to toxicants based on the results of different non-clinical and preclinical tests. For this, data was collected from different reliable electronic databases such as PubMed, Google Scholar, and ScienceDirect, etc. The results of this investigation demonstrated that FA and its derivatives have potent hepatoprotective effects against oxidative stress and inflammation-related damage. The findings also revealed that these protective effects are due to the antioxidant and anti-inflammatory effects of the chemical compound. FA and its analogues significantly inhibit free radical generation and hinder the effects of proinflammatory markers and inflammatory enzymes, resulting in diminished cytotoxic and apoptotic hepatocyte death. The compounds also prevent intracellular lipid accumulation and provide protective effects.

Ferulic Acid Inhibits Arsenic-Induced Colon Injury by Improving Intestinal Barrier Function.

The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic-induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) activation and nuclear factor-kappa B (NF-κB) pathway blocking. Based on the antioxidant and anti-inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic-induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco-2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF-κB and Nrf2/HO-1 pathway in colon and Caco-2 cells were also detected. As shown in our data, FA inhibited arsenic-induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down-regulated expression of tight junction (TJ) proteins (Claudin-1, Occludin, and ZO-1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco-2 cells. In addition to suppressing the activation of NF-κB pathway, FA retrieved the activation of Nrf2/HO-1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic-induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

Ferulic acid grafted into ß-cyclodextrin nanosponges ameliorates Paraquat-induced human MRC-5 fibroblast injury.

Paraquat (PQ) is a commercially important and effective herbicide in the world. Nevertheless, it has higher toxicity causing acute organ damage and different complications, mainly in the lungs and kidneys. Ferulic acid (FA), 4-hydroxy-3-methoxycinnamic acid imposes multiple pharmacological impacts. No protective effect of FA on PQ poisoning-caused human embryonic lung fibroblast damage has not been reported. Despite their many beneficial effects, FA is characterized by poor water solubility, low bioavailability, and phytochemical instability. To solve the problem, ß-cyclodextrin nanosponge (ß-CD NSs) was utilized to increase the solubility of FA so that it was grafted into ß-CD NSs to establish ß-CD@FA NSs. The purpose of this work was to examine for the first time the protective effect of ß-CD@FA NS on MRC-5 human lung cells damages induced by PQ poisoning. MTS assay was performed to investigate the viability of MRC-5 cells at different concentrations of FA/ß-CD@FA NSs when cells were co-cultured with 0.2 µg/mL PQ. The flow cytometry study was carried out to determine apoptosis. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were detected using appropriate biochemistry kits. Compared with the PQ group, the cell activity, CAT, and SOD levels were significantly increased in the FA and chiefly in ß-CD@FA NSs intervention groups, whereas apoptosis and MDA levels were markedly decreased. The inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 22 (IL-22) were detected. The results demonstrate that ß-CD@FA NSs can inhibit PQ-induced cell damage by enhancing antioxidant stress capacity and regulation of inflammatory responses.

Ferulic acid nanoemulsion as a promising anti-ulcer tool: in vitro and in vivo assessment.

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.

Protective effects of ferulic acid on embryonic development by improving antioxidant function in broilers embryo of thermal manipulation.

This study aimed to elucidate the effects of broiler embryos soaked in ferulic acid (FA) solution on alleviating the negative impact of thermal manipulation (TM) on chicken embryo development and to provide a theoretical and experimental basis for applying TM and FA in the poultry feeding industry. A total of 120 broiler fertilized eggs were randomly divided into three groups: control group, TM group, and comprehensive group (TM + FA), with 40 eggs in each group. The TM group and the comprehensive group from the 7th embryonic age to the 16th embryonic age received TM for ten days, treated with a temperature of 39.5 °C and relative humidity of 65% for 18 h a day. In the comprehensive group, broiler embryos were immersed in FA solution at a concentration of 80 mg/L for 6 min at 16:00 every day from the 6th to the 8th embryo age. They were incubated continuously after being soaked until the chicks hatched. The results showed that the rates of dead embryos and weak chicks in the TM group were significantly higher than those in the control group and comprehensive group. Chick body temperatures of the TM group and comprehensive group were significantly lower than those of the control group. The heart weights of the TM group and comprehensive group were significantly lower than those of the control group, and the leg weights of the TM group were significantly decreased compared with those of the control group and comprehensive group. The SOD activity of serum in the comprehensive group was significantly higher than that in the control group and TM group, while the CAT activity of serum in the comprehensive group and control group was significantly higher than that in the TM group; however, there was no difference between the comprehensive group and control group. The activities of SOD and CAT in the liver were significantly higher than those of the TM group; however, the MDA content of the liver in the comprehensive group and control group was significantly lower than that of the TM group. The gene expression of Nrf2 and SOD in the comprehensive group and TM group was significantly higher than that in the control group; however, there was no significant difference between the comprehensive group and TM group. Soaking broiler embryonic eggs in an FA solution can improve the antioxidant capacity of the liver by upregulating Nrf2-Keap1 signal pathway-related gene expression. FA can effectively alleviate the side effects of TM on chicken embryos and does not impact the effects of TM.

Enemies or Allies? Hormetic and Apparent Non-Dose-Dependent Effects of Natural Bioactive Antioxidants in the Treatment of Inflammation.

This review aims to analyze the emerging number of studies on biological media that describe the unexpected effects of different natural bioactive antioxidants. Hormetic effects, with a biphasic response depending on the dose, or activities that are apparently non-dose-dependent, have been described for compounds such as resveratrol, curcumin, ferulic acid or linoleic acid, among others. The analysis of the reported studies confirms the incidence of these types of effects, which should be taken into account by researchers, discarding initial interpretations of imprecise methodologies or measurements. The incidence of these types of effects should enhance research into the different mechanisms of action, particularly those studied in the field of basic research, that will help us understand the causes of these unusual behaviors, depending on the dose, such as the inactivation of the signaling pathways of the immune defense system. Antioxidative and anti-inflammatory activities in biological media should be addressed in ways that go beyond a mere statistical approach. In this work, some of the research pathways that may explain the understanding of these activities are revised, paying special attention to the ability of the selected bioactive compounds (curcumin, resveratrol, ferulic acid and linoleic acid) to form metal complexes and the activity of these complexes in biological media.