Alzheimer’s disease (AD) is an age-related multifactorial neurodegenerative disorder characterized by severe central cholinergic neuronal loss, gradually contributing to cognitive dysfunction and ...impaired motor activity, resulting in the brain’s cell death at the later stages of AD. Although the etiology of AD is not well understood, however, several factors such as oxidative stress, deposition of amyloid-β (Aβ) peptides to form Aβ plaques, intraneuronal accumulation of hyperphosphorylated tau protein, and low level of acetylcholine are thought to play a major role in the pathogenesis of AD. There is practically no drug for AD treatment that can address the basic factors responsible for the neurodegeneration and slow down the disease progression. The currently available therapies for AD in the market focus on providing only symptomatic relief without addressing the aforesaid basic factors responsible for the neurodegeneration. Ferulic acid (FA) is a phenol derivative from natural sources and serves as a potential pharmacophore that exerts multiple pharmacological properties such as antioxidant, neuroprotection, Aβ aggregation modulation, and anti-inflammatory. Several FA based hybrid analogs are under investigation as a multi-target directed ligand (MTDLs) to develop novel hybrid compounds for the treatment of AD. In the present review article, we are focused on the critical pathogenic factors responsible for the onset of AD followed by the developments of FA pharmacophore-based hybrids compounds as a novel multifunctional therapeutic agent to address the limitations associated with available treatment for AD. The rationale behind the development of these compounds and their pharmacological activities in particular to their ChE inhibition (ChEI), neuroprotection, antioxidant property, Aβ aggregation modulation, and metal chelation ability, are discussed in detail. We have also discussed the discovery of caffeic and cinnamic acids based MTDLs for AD. This review paper provides an in-depth insight into the research progress and current status of these novel therapeutics in AD and prospects for developing a druggable molecule with desired pharmacological affinity and reduced toxicity for the management of AD.
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•This review article summarizes the development of druggable Ferulic acid (FA) and analogs-derivatives to manage Alzheimer’s disease (AD).•The potential impact of the developed compounds on various critical aspects of AD are discussed in detail.•The current research on the development of FA will hopefully add disease-modifying properties to symptomatic treatment for AD.
Nowadays, the synthesis of (semi)aromatic polymers from lignin derivatives is of major interest, as aromatic compounds are key intermediates in the manufacture of polymers and lignin is the main ...source of aromatic biobased substrates. Phenols with a variety of chemical structures can be obtained from lignin deconstruction; among them, vanillin and ferulic acid are the main ones. Depending on the phenol substrates, different chemical modifications and polymerization pathways are developed, leading to (semi)aromatic polymers covering a wide range of thermomechanical properties. This review discusses the synthesis and properties of thermosets (vinyl ester resins, cyanate ester, epoxy, and benzoxazine resins) and thermoplastic polymers (polyesters, polyanhydrides, Schiff base polymers, polyacetals, polyoxalates, polycarbonates, acrylate polymers) prepared from vanillin, ferulic acid, guaiacol, syringaldehyde, or 4‐hydroxybenzoic acid.
This review presents the major interests of lignin derivatives such as vanillin, ferulic acid, guaiacol, syringaldehyde, and 4‐hydroxybenzoic acid as a source of novel semi‐aromatic biobased polymers. The structure–property relationships of these materials are discussed.
•Ferulic acid inhibited α-amylase/α-glucosidase by mixed/non-competitive mechanisms.•Secondary structures of α-amylase/α-glucosidase were changed by binding ferulic acid.•Non-covalent bonding was the ...main force between ferulic acid and α-amylase/α-glucosidase.•Ferulic acid is a potential inhibitor of the activity of α-amylase/α-glucosidase.
The inhibitory mechanisms of ferulic acid against α-amylase and α-glucosidase were investigated by enzyme kinetic analysis, circular dichroism (CD), Fourier-transform infrared (FT-IR) spectroscopy, fluorescence quenching and molecular docking. Results indicated that ferulic acid strongly inhibited α-amylase (IC50: 0.622 mg ml−1) and α-glucosidase (IC50: 0.866 mg ml−1) by mixed and non-competitive mechanisms, respectively. CD spectra and fluorescence intensity measurements confirmed that the secondary structure of α-amylase and α-glucosidase were changed and the microenvironments of certain amino acid residues were modulated by the binding of ferulic acid. FT-IR spectra indicated that the interaction between ferulic acid and α-amylase/α-glucosidase mainly involved in non-covalent bonds. Molecular docking further demonstrated that the interaction forces between ferulic acid and α-amylase/α-glucosidase were hydrogen bonds, with the binding energy of −5.30 to −5.10 and −5.70 kcal mol−1, respectively. This study might provide a theoretical basis for the designing of novel functional foods with ferulic acid.
Lignin is identified as a promising candidate in renewable energy and bioproduct manufacturing due to its high abundance, polymeric structure, and biochemical properties of monomers. Thus, emerging ...opportunities exist in generating high-value small molecules from lignin through depolymerization. This review aims at providing an overview of the major technologies of lignin depolymerization. The feasibility of large-scale implementation of these technologies, including thermal, biological, and chemical depolymerizations, are discussed in relation to potential industrial applications. Lignin as a renewable alternative to petroleum-based chemicals has been well documented. This review attempts to emphasize potential applications of lignin-derived monomers and their derivatives as bioactives in food, natural health product, and pharmaceutical sectors. The critical review of the prospects and challenges of lignin-derived bioproducts reveals that the advancement of research and development is required to explore the applications of depolymerization of lignins to their full potential.
Estimates of the activity of antioxidants in the literature often appear inconsistent. In the specific case of the DPPH∙ test, the diversity of measurements may arise from variations in the protocols ...followed. This paper proposes an unbiased method which models the reduction mechanism. This method is applied to the reduction of DPPH∙ by ferulic acid. A scheme with eight coupled reactions is proposed and has been validated on different solvents and using a wide range of DPPH ̇, ferulic acid, and 5,5′-diferulic acid concentrations, and verified using data from the literature on ferulic acid activity. This modeling approach permits a correction to the bias of the 8th reaction (spontaneous reduction of DPPH ̇), because of its sensitivity to solvent, which in most cases is not taken into account. The best experimental strategy to determine the Efficient Concentration of ferulic acid to reduce 20% (EC20) and 50% (EC50) of DPPH∙ is then detailed in terms of initial DPPH∙ concentrations and the duration of the experiment.
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•We have established a stoichiokinetic model of DPPH∙ reduction by ferulic acid.•Different concentrations, solvents and data have validated the 8-reaction model.•Solvents can impact the spontaneous DPPH∙ reduction more than the ferulic acid action.•The EC50 of ferulic acid is dependent on the low initial concentrations of DPPH ̇.•The DPPH∙ concentration and duration of experiments have been optimized for EC50.
Ferulic acid, a kind of phenolic substance widely existing in plants, is an important active component of many traditional Chinese medicines. So far, it has been proved that ferulic acid has a ...variety of biological activities, especially in oxidative stress, inflammation, vascular endothelial injury, fibrosis, apoptosis and platelet aggregation. Many studies have shown that ferulic acid can inhibit PI3K/AKT pathway, the production of ROS and the activity of aldose reductase. The anti-inflammatory effect of ferulic acid is mainly related to the levels of PPAR γ, CAM and NF-κ B and p38 MAPK signaling pathways. Ferulic acid not only protects vascular endothelium by ERK1/2 and NO/ET-1 signal, but also plays an anti-fibrosis role by TGF-β/Smad and MMPs/TIMPs system. Moreover, ferulic acid has ant-apoptotic and anti-platelet effects. In addition to the pharmacological effects of ferulic acid, its pharmacokinetics and derivatives were also discussed in this paper. This review provides the latest summary of the latest research on ferulic acid.
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•This is a pioneer review of ferulic acid and its derivatives.•Ferulic acid and its derivatives present diverse biological functions.•Ferulic acid is promising molecule to treat vascular disorders.•Ferulic acid and its derivatives have strong antioxidant activity.
Ferulate dehydrodimers and the more recently discovered dehydrotrimers play an important role in the cell wall architecture of plant-based foods and forages. High-performance liquid chromatography ...methods to determine ferulate dimers often lack specificity; methods for trimers did not exist yet. A method for the determination of 11 cell wall-bound ferulate dehydrodimers and -trimers was developed, including the crucial separation of the di/trimers from the often dominating phenolic monomers. Validation parameters for the basic calibration of the dimers and trimers met our acceptance criteria. However, the matrix calibration revealed that lignin-rich matrices lead to problems with precision and accuracy that likely can be addressed by using a more specific detection, that is, mass spectrometric detection, next to improved sample preparation procedures. The method was used to analyze low-lignin fibers from corn, wheat, and rye grains, wild rice, asparagus, and sugar beet. With the exception of wild rice, the 5-5/8-O-4-, 8-O-4/8-O-4-, and 8-8(aryltetralin)/8-O-4-dehydrotrimers were detected in all analyzed samples, however, often in amounts below the limit of quantitation.
Postharvest fruit infection by Alternaria alternata results in significant food waste and economic losses. Methyl ferulate (MF) emerges as a safe and potent plant-derived agent against A. alternata, ...yet its effectiveness is hindered by poor water solubility, limiting its wide application in postharvest preservation. This study aimed to address this issue by utilizing naturally derived grapefruit essential oil (GEO) as the dissolution carrier for MF, followed by the preparation of a nanosystem to stabilize it through ultrasound-assisted methods. At 20 mg/mL MF loading, nanoemulsions (NEs) exhibited the smallest droplet size (15.66 nm), highest centrifugation stability (Ke of 2.32 %), and optimal storage stability (15.44 nm after 30 d at 4 ℃). Importantly, MF in the nanosystem (named MN) acts as an Ostwald ripening inhibitor and reduces the interfacial tension, which in turn benefits the stability of this system. In vitro, MN showed enhanced inhibition of A. alternata hyphal growth (an inhibitory rate in potato dextrose broth medium of 99.07 ± 1.32 %) and a fourfold reduction in MIC compared to free MF. MN damaged A. alternata plasma membranes and induced reactive oxygen species (ROS) oxidative stress. In vivo, MN inhibited black spot disease and toxin production of A. alternata in pears. Additionally, MN incorporated into carboxymethylcellulose sodium (CMC) prolonged the shelf life of Korla pears and cherry tomatoes by delaying weight loss and maintaining their firmness and intrinsic nutrients. Therefore, this study broadened the application of MF, offering a viable approach for postharvest preservation of fruit infected by A. alternata.
●Methyl ferulate (MF) was stabilized in grapefruit essential oil-based nanosystem.●MF served as a ripening inhibitor to enhance the stability of nanoemulsions (NEs).●Stabilized MF in NEs showed a fourfold reduction in MIC against A. alternata.●NE-20 inhibited black spot and A. alternata toxins accumulation in Korla pear.●NE-20 preserved the quality of Korla pears and cherry tomatoes.
Alzheimer's disease (AD) is the most common form of dementia and its prevention and treatment is a worldwide issue. Many natural components considered to be effective against AD have been identified. ...However, almost all clinical trials of these components for AD reported inconclusive results. We thought that multiple factors such as amyloid β (Aβ) and tau progressed the pathology of AD and that a therapeutic effect would be obtained by using multiple active ingredients with different effects. Thus, in this study, we treated ferulic acid (FA), phosphatidylserine (PS) and curcumin (Cur) in combination or alone to APPswe/PS1dE9 transgenic mice and evaluated cognitive function by Y-maze test. Consequently, only the three-ingredient group exhibited a significant improvement in cognitive function compared to the control group. In addition, we determined the amounts of Aβ, brain-derived neurotrophic factor (BDNF), interleukin (IL)-1β, acetylcholine and phosphorylated tau in the mouse brains after the treatment. In the two-ingredient (FA and PS) group, a significant decrease in IL-1β and an increasing trend in acetylcholine were observed. In the Cur group, significant decreases in Aβ and phosphorylated tau and an increasing trend in BDNF were observed. In the three-ingredient group, all of them were observed. These results indicate that the intake of multiple active ingredients with different mechanisms of action for the prevention and treatment of AD.
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