Metabolic diseases are abnormal conditions that impair the normal metabolic process, which involves converting food into energy at a cellular level, and cause difficulties like obesity and diabetes. The study aimed to investigate how ferulic acid (FA) and its derivatives could prevent different metabolic diseases and disorders and to understand the specific molecular mechanisms responsible for their therapeutic effects. Information regarding FA associations with metabolic diseases and disorders was compiled from different scientific search engines, including Science Direct, Wiley Online, PubMed, Scopus, Web of Science, Springer Link, and Google Scholar. This review revealed that FA exerts protective effects against metabolic diseases such as diabetes, diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, obesity, and diabetic hypertension, with beneficial effects on pancreatic cancer. Findings also indicated that FA improves insulin secretion by increasing Ca2+ influx through the L-type Ca2+ channel, thus aiding in diabetes management. Furthermore, FA regulates the activity of inflammatory cytokines (TNF-α, IL-18, and IL-1β) and antioxidant enzymes (CAT, SOD, and GSH-Px) and reduces oxidative stress and inflammation, which are common features of metabolic diseases. FA also affects various signaling pathways, including the MAPK/NF-κB pathways, which play an important role in the progression of diabetic neuropathy and other metabolic disorders. Additionally, FA regulates apoptosis markers (Bcl-2, Bax, and caspase-3) and exerts its protective effects on cellular destruction. In conclusion, FA and its derivatives may act as potential medications for the management of metabolic diseases.

Reducing the risk of wound infection is an urgent issue health priority. Antibacterial polysaccharide-based hydrogels have attracted great attention for infectious wounds, attributed to their safe antimicrobial performance and natural non-toxicity and biodegradability advantages. In this study, the \"all-in-one\" self-adaptive and injectable cationic guar gum (CG)-based polysaccharide hydrogels (FA-TOB/CG) loaded with bioactive complexes were developed for infectious wound healing. The constructed antioxidant and antibacterial ferulic acid (FA)-tobramycin (TOB) bioactive complexes (FA-TOB) were used as the cross-linking agent and introduced into the CG matrix to construct the FA-TOB/CG hydrogel with a three-dimensional porous structure. The sterilization rates of FA-TOB/CG hydrogel against S. aureus and E. coli reached 98 % and 80 % respectively. In addition, the FA-TOB/CG also exhibits enhanced antioxidant performances (DPPH: > 40 %; ABTS: > 90 %; ·OH: > 50 %). More importantly, FA-TOB/CG hydrogel also showed the ability to sustain the release of FA and TOB. These superiorities of the FA-TOB/CG hydrogel enabled it to provide a moist wound environment and promote wound healing by eliminating bacteria, modulating the local inflammatory response, and accelerating collagen deposition and vascular regeneration. Thus, this study may enlarge a new sight for developing multifunctional dressings by incorporating bioactive complexes into polysaccharide hydrogels for infected wounds.

Caldimonas thermodepolymerans, a Gram-negative, moderately thermophilic bacterium, exhibits a remarkable biotechnological potential. Given the presence of genes in its genome dedicated to the metabolization of ferulic acid (FA), this study aimed to explore the bacterium\'s capability for biotransforming FA into high-value metabolites. The results unequivocally demonstrate the bacterium\'s proficiency in the efficient and rapid conversion of FA into vanillyl alcohol (VOH) and vanillic acid (VA). By manipulating key cultivation parameters, such as adjusting initial FA doses and varying cultivation periods, the product profile can be tailored. Higher initial doses and shorter cultivation periods favor the production of VOH, while lower FA doses and extended cultivation periods lead to the predominant formation of VA. Furthermore, the process can be operated in a repeated-batch scenario. This underscores the potential of C. thermodepolymerans for industrial biotransformation of FA, presenting a promising avenue for leveraging its capabilities in practical applications.

Vanillin is one of the world\'s most extensively used flavoring agents with high application value. However, the yield of vanillin biosynthesis remains limited due to the low efficiency of substrate uptake and the inhibitory effect on cell growth caused by vanillin. Here, we screened high-efficiency ferulic acid importer TodX and vanillin exporters PP_0178 and PP_0179 by overexpressing genes encoding candidate transporters in a vanillin-producing engineered Escherichia coli strain VA and further constructed an autoregulatory bidirectional transport system by coexpressing TodX and PP_0178/PP_0179 with a vanillin self-inducible promoter ADH7. Compared with strain VA, strain VA-TodX-PP_0179 can efficiently transport ferulic acid across the cell membrane and convert it to vanillin, which significantly increases the substrate utilization rate efficiency (14.86%) and vanillin titer (51.07%). This study demonstrated that the autoregulatory bidirectional transport system significantly enhances the substrate uptake efficiency while alleviating the vanillin toxicity issue, providing a promising viable route for vanillin biosynthesis.

A series of ferulic acid dimers were designed, synthesized, and evaluated for anti-TMV activity. Biological assays demonstrated that compounds A6, E3, and E5 displayed excellent inactivating against tobacco mosaic virus (TMV) with EC50 values of 62.8, 94.4, and 85.2 μg mL-1, respectively, which were superior to that of ningnanmycin (108.1 μg mL-1). Microscale thermophoresis indicated that compounds A6, E3, and E5 showed strong binding capacity to TMV coat protein with binding affinity values of 1.862, 3.439, and 2.926 μM, respectively. Molecular docking and molecular dynamics simulation revealed that compound A6 could firmly bind to the TMV coat protein through hydrogen and hydrophobic bonds. Transmission electron microscopy and self-assembly experiments indicated that compound A6 obviously destroyed the integrity of the TMV particles and blocked the virus from infecting the host. This study revealed that A6 can be used as a promising leading structure for the development of antiviral agents by inhibiting TMV self-assembly.

Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H2O2 evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new \"green\" carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations.

To obtain more sustainable and active food packaging materials, PHBV films containing 5% wt. of phenolic compounds with different molecular structures (ferulic acid, vanillin, and catechin) and proved antioxidant and antimicrobial properties were obtained by melt blending and compression molding. These were characterized by their structural, mechanical, barrier, and optical properties, as well as the polymer crystallization, thermal stability, and component migration in different food simulants. Phenolic compounds were homogenously integrated within the polymer matrix, affecting the film properties differently. Ferulic acid, and mainly catechin, had an anti-plasticizing effect (increasing the polymer glass transition temperature), decreasing the film extensibility and the resistance to breaking, with slight changes in the elastic modulus. In contrast, vanillin provoked a plasticizing effect, decreasing the elastic modulus without notable changes in the film extensibility while increasing the water vapor permeability. All phenolic compounds, mainly catechin, improved the oxygen barrier capacity of PHBV films and interfered with the polymer crystallization, reducing the melting point and crystallinity degree. The thermal stability of the material was little affected by the incorporation of phenols. The migration of passive components of the different PHBV films was lower than the overall migration limit in every simulant. Phenolic compounds were released to a different extent depending on their thermo-sensitivity, which affected their final content in the film, their bonding forces in the polymer matrix, and the simulant polarity. Their effective release in real foods will determine their active action for food preservation. Catechin was the best preserved, while ferulic acid was the most released.

Introduction Periodontitis, a persistent inflammatory condition, impacts the tissues supporting teeth. Beyond mechanically eradicating the biofilm, additional host-modulating agents can aid in the treatment of periodontitis. Among these, gels are a very popular choice for use in the field of dentistry as these systems boast high biocompatibility and bioadhesiveness. These qualities make them easily administered and fabricated. They are typically placed into the periodontal site via wide-port needle syringes. Many investigations have demonstrated that hydrogels possess the ability for controlled drug release and aid in periodontal wound healing. Hence, this study aimed to develop a ferulic acid hydrogel and assess its effectiveness for managing periodontitis. Materials and methods Ferulic acid hydrogel was prepared followed by haemolysis assay and biocompatibility assay. After the in vitro analysis, a clinical trial was conducted: 20 patients were divided into Group A (comprising patients in whom scaling and root planing (SRP) was done) and Group B (comprising patients in whom SRP along with hydrogel application was done). Each patient\'s pocket depth (PD), clinical attachment loss (CAL), gingival index (GI), and plaque index (PI) were recorded at baseline and at three months. Intergroup and intragroup comparisons of the parameters were made. Results Ferulic acid hydrogels exhibit a minimal ratio of red blood cell destruction, indicating their low haemolytic activity. Beyond 94 hours, ferulic acid hydrogel demonstrates minimal toxicity towards human fibroblasts, suggesting it has good biocompatibility. When clinical parameters were compared after three months of treatment with SRP alone, significant reductions were observed in all parameters. However, when hydrogel application was done along with SRP, greater reduction was seen in terms of all clinical parameters indicating the efficacy of the ferulic acid hydrogel as an adjunct.  Conclusion Ferulic acid has distinct haemolytic activity as well as good biocompatibility. Its use also led to a considerable reduction in all clinical parameters, necessitating its role as a local drug delivery agent in the treatment of periodontitis.

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.

Phenolic compounds represent natural compounds endowed with diverse biological functionalities. However, their inherent limitations, characterized by poor water solubility and low oral bioavailability, limit their broader applications. Encapsulation delivery systems are emerging as a remedy, able to ameliorate these limitations by enhancing the stability and solubility of phenolic compounds. In this study, a novel, customized pH-driven approach was developed by determining the optimal deprotonation and protonation points of three different types of polyphenols: ferulic acid, resveratrol, and rhein. The polyphenols were successfully encapsulated in a casein carrier. The solubility, stability, LogD, and LogS curves of the three polyphenols at different pH values were analyzed to identify the optimal deprotonation points for ferulic acid (pH 9), resveratrol (pH 11), and rhein (pH 10). Based on these findings, three different nanoparticles were prepared. The encapsulation efficiencies of the three phenolic compounds were 95.86%, 94.62%, and 94.18%, respectively, and the casein nanoparticles remained stable at room temperature for seven days. FTIR spectroscopy, fluorescence spectroscopy, and molecular docking study substantiated the encapsulation of phenolic compounds within the hydrophobic core of casein-based complexes, facilitated by hydrogen bonding interactions and hydrophobic interactions. Furthermore, the analysis of antioxidant activity elucidated that casein nanoparticles heightened both the water solubility and antioxidant efficacy of the phenolic compounds. This customized encapsulation technique, by establishing a transitional pH value, resolves the challenges of chemical instability and facile degradation of polyphenols under alkaline conditions in the application process of pH-driven methods. It presents novel insights for the application of polyphenols in the domains of food and biomedical fields.