Cinnamic Acid Derivatives: Recent Discoveries and Development Strategies for Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline and memory impairment. It is characterized by the accumulation of Amyloid-beta (Aß) plaques, the abnormal phosphorylation of tau protein forming neurofibrillary tangles, and is often accompanied by neuroinflammation and oxidative stress, which contribute to neuronal loss and brain atrophy. At present, clinical anti-AD drugs are mostly single-target, improving the cognitive ability of AD patients, but failing to effectively slow down the progression of AD. Therefore, research on effective multi-target drugs for AD has become an urgent problem to address. The main derivatives of hydroxycinnamic acid, caffeic acid, and ferulic acid, are widely present in nature and have many pharmacological activities, such as antimicrobial, antioxidant, anti-inflammatory, neuroprotective, anti-Aß deposition, and so on. The occurrence and development of AD are often accompanied by pathologies, such as oxidative stress, neuroinflammation, and Aß deposition, suggesting that caffeic acid and ferulic acid can be used in the research on anti-AD drugs. Therefore, in this article, we have summarized the multi-target anti-AD derivatives based on caffeic acid and ferulic acid in recent years, and discussed the new design direction of cinnamic acid derivatives as backbone compounds. It is hoped that this review will provide some useful strategies for anti-AD drugs based on cinnamic acid derivatives.

Preparation and Antibacterial Properties of Polyelectrolyte Complexed Nanoparticles Aggregated from PHMG and Sodium Caffeate.

In this study, we synthesized polyelectrolyte complexed nanoparticles using an ion exchange reaction between poly(hexamethylene guanidine hydrochloride) and sodium caffeate. The morphology of the obtained antiparticle was observed by scanning electron microscopy, and FT-IR and XPS were employed for the structural characterization. The antimicrobial properties of E. coli and S. aureus were characterized through minimum inhibitory concentration (MIC), growth curve analysis, plate colony counting method, and crystal violet method. Notably, the sample showed a 100% bactericidal rate against E. coli at 0.095 µg/mL and against S. aureus at 0.375 µg/mL within 1 h, demonstrating excellent antimicrobial performance against E. coli and S. aureus. The CA-PHMG-containing acrylic resin coatings exhibited exceptional antimicrobial and antiadhesive properties when examined under an inverted fluorescence microscope, particularly at a 4% weight concentration of the antibacterial agent. This study holds vast potential for development in the field of antimicrobial coatings.

Productions of Th2 cytokines, IL-4 and IL-10, were enhanced via the function of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells treated with caffeic acid phenethyl ester.

OBJECTIVES: Interleukin (IL)-2 production by mouse spleen cells stimulated with an anti-CD3 antibody is significantly enhanced by caffeic acid phenethyl ester (CAPE), a major constituent of Chinese propolis (CP). In this study, we evaluated the functional significance of IL-2 in CAPE-treated activated spleen cells. METHODS: Mouse spleen cells were stimulated with an anti-CD3 monoclonal antibody in the presence of CAPE. Cytokine production was examined using an enzyme-linked immunosorbent assay (ELISA). Messenger RNA level expression was examined via reverse transcription quantitative polymerase chain reaction (RT-PCR). IL-2 function was assessed using IL-2 and a neutralizing antibody. Spleen cell subsets were identified and characterized using flow cytometry. RESULTS: CAPE treatment of anti-CD3 antibody-stimulated spleen cells reduced IFN-γ production, then enhanced IL-2 production, followed by enhancement of IL-4 and IL-10 production. The Th2 cytokine production enhancing effects of CAPE were completely abolished by addition of an anti-IL-2 neutralizing antibody. In the absence of CAPE, exogenously added IL-2 could enhance IL-4 production to a lesser degree, but did not stimulate IL-10 production, in stimulated spleen cells. Interestingly, CAPE significantly reduced the proportions of CD4+ and CD8+ cells, and increased those of CD4-CD8- cells among anti-CD3 stimulated spleen cells, in the presence or absence of anti-IL-2 neutralizing antibody treatment. CONCLUSIONS: CAPE reduced IFN-γ production, then enhanced IL-4 and IL-10 production via the activity of specifically elevated IL-2 in stimulated spleen cells. CAPE exerted these effects in a CD4- CD8- cell specific manner.

Antioxidant activity of Zuccagnia-type propolis: A combined approach based on LC-HRMS analysis of bioanalytical-guided fractions and computational investigation.

This study reports a combined approach to assess the antioxidant activity of Zuccagnia-type propolis. Fractions exhibiting the highest antioxidant activities evidenced by DPPH, a ß-carotene bleaching and superoxide radical scavenging activity-non-enzymatic assays, were processed by LC-HRMS/MS to characterize the relevant chemical compounds. A computational protocol based on the DFT calculations was used to rationalize the main outcomes. Among the 28 identified flavonoids, caffeic acids derivatives were in the fraction exhibiting the highest antioxidant activity, with 1-methyl-3-(4'-hydroxyphenyl)-propyl caffeic acid ester and 1-methyl-3-(3',4'-dihydroxyphenyl)-propyl caffeic acid ester as major components. Results clearly showed roles of specific chemical motifs, which can be supported by the computational analysis. This is the first report ascribing the antioxidant ability of Zuccagnia-type propolis to its content in specific caffeic acid derivatives, a potential source of radical scavenging phytochemicals. The proposed protocol can be extended to the study of other plant-products to address the most interesting bioactive compounds.

Phytochemical Characteristics and Antimicrobial Effects of Nonea rossica (Boraginaceae) Extracts.

Phytochemical characteristics and antimicrobial properties of extracts were studied in Nonea rossica Steven (Boraginaceae), which is widespread in Russia. The aerial part (herb) of N. rossica was harvested from a steppe meadow in the Novosibirsk region during flowering. The qualitative composition of biologically active compounds (BACs) was determined by thin-layer chromatography. Quantitative assays were carried out by spectrophotometry; flavonoids, hydroxycinnamic acids, and coumarin-like compounds were measured with reference to rutin, caffeic acid, and coumarin, respectively. Antimicrobial activity was determined by the serial dilution method. Gram-positive bacterial (Staphylococcus aureus ATCC 6538 FDA 209P and Bacillus cereus ATCC 10702) and fungal (Candida albicans NCTC 885-653) strains were used as test cultures. Phenolic BACs (hydroxycinnamic acids, flavonoids, and coumarins) were detected, and their quantitative contents determined. The highest yield of phenolic BACs was achieved using 40-70% ethanol as an extractant. Antimicrobial activity against S. aureus and B. cereus and antifungal activity against C. albicans were detected in N. rossica herb extracts prepared using 40-70% ethanol. The extracts were tested for the contents of caffeic acid and coumarin. Synergistic interactions of these compounds determined the bactericidal and fungistatic properties of the extracts.

Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1.

BACKGROUND: Ferroptosis of keratinocytes is closely associated with amplification of skin inflammation in psoriasis. This study focuses on unlocking the role of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and understanding the underlying mechanistic basis. METHODS: The interaction between early growth response protein 1 (EGR1) and chac glutathione specific γ­glutamylcyclotransferase 1 (CHAC1) was predicted by bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase reported assays. Their expressions in primary human epidermal keratinocytes were altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer). Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1 in keratinocytes were analyzed by qRT-PCR or Western blot. RESULTS: Increased expressions of EGR1 and CHAC1 were detected in keratinocytes with Erastin treatment. CA (100 µM) antagonized Erastin (10 µM)-induced decrease in viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects. Moreover, EGR1 overexpression and CA mutually counteracted their effects on Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1 knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown and CHAC1 overexpression reversed each other's effects. CONCLUSION: CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1 to dampen inflammation of keratinocytes in psoriasis. This study providing new compounds and candidate targets for the clinical treatment of psoriasis.

Caffeic acid modulates intestinal microbiota, alleviates inflammatory response, and enhances barrier function in a piglet model challenged with lipopolysaccharide.

Young animals are highly susceptible to intestinal damage due to incomplete intestinal development, making them vulnerable to external stimuli. Weaning stress in piglets, for instance, disrupts the balance of intestinal microbiota and metabolism, triggering intestinal inflammation and resulting in gut damage. Caffeic acid (CA), a plant polyphenol, can potentially improve intestinal health. Here, we evaluated the effects of dietary CA on the intestinal barrier and microbiota using a lipopolysaccharide (LPS)-induced intestinal damage model. Eighteen piglets were divided into three groups: control group (CON), LPS group (LPS), and CA + LPS group (CAL). On the 21st and 28th day, six piglets in each group were administered either LPS (80 µg/kg body weight; Escherichia coli O55:B5) or saline. The results showed that dietary CA improved the intestinal morphology and barrier function, and alleviated the inflammatory response. Moreover, dietary CA also improved the diversity and composition of the intestinal microbiota by increasing Lactobacillus and Terrisporobacter while reducing Romboutsia. Furthermore, the LPS challenge resulted in a decreased abundance of 14 different bile acids and acetate, which were restored to normal levels by dietary CA. Lastly, correlation analysis further revealed the potential relationship between intestinal microbiota, metabolites, and barrier function. These findings suggest that dietary CA could enhance intestinal barrier function and positively influence intestinal microbiota and its metabolites to mitigate intestinal damage in piglets. Consuming foods rich in CA may effectively reduce the incidence of intestinal diseases and promote intestinal health in piglets.

Nanoarchitecturing of Mo2C nanospheres on carbon cloth as an electrochemical sensing platform for determination of caffeic acid in tea samples.

In the present paper, carbon cloth (CC) as a flexible substrate was modified by molybdenum carbide nanospheres (Mo2C NSs @CC) by the drop-coating method to develop a sensitive electrochemical platform for detecting caffeic acid. The uniform Mo2C NSs were prepared via an easy route followed by pyrolyzing the precursor of the Mo-polydopamine (Mo-PDA) NSs. The Mo2C NSs were characterized and analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy/energy dispersive X-ray spectroscopy (FE-SEM/EDS), Raman spectroscopy (RS), and electrochemical methods. CC not only gave a flexible feature to the sensor but also provided a larger surface area for Mo2C NSs. Meanwhile, the excellent conductivity and large electroactive specific surface area of Mo2C NSs exhibited excellent electrocatalytic performance for caffeic acid determination. The developed sensor showed high sensitivity and selectivity, good reproducibility, and long-term stability with a limit of detection (LOD) and a wide linear range of 0.001 µM (S/N = 3) and 0.01-50 µM, respectively. In addition, the Mo2C NSs @CC sensor showed a promising application prospect for the detection of caffeic acid in green and black tea samples, indicating its importance in food safety and the food industry.

Effects of the covalent conjugation between caffeic acid and peanut allergen protein Ara h1 on the antigenicity and structure of Ara h1.

Ara h1 was the highest content of peanut allergen protein, identified as a biomarker of peanut allergen. In this study, Ara h1 was covalently complexed with caffeic acid (CA) to research the effects of covalent conjugation on the antigenicity and protein structural properties of Ara h1. After the covalent complexing of Ara h1 and CA, the IgG-binding capacity of Ara h1 was reduced compared with that of control Ara h1. Moreover, the structure of Ara h1 changed from ordered to disordered, the number of intermolecular hydrogen bonds decreased, and some hydrophobic groups were exposed or hydrophobic peptides were released. The carboxyl group in CA reacted with the amino group in Ara h1. The digestibility of Ara h1-CA was increased. The antigenicity of Ara h1-CA was undetectable after 30 min of digestion in vitro. These findings can serve as a reference for further research on hypoallergenic peanut products.

A two-pronged approach to inhibit ferroptosis of MSCs caused by the iron overload in postmenopausal osteoporosis and promote osseointegration of titanium implant.

Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.

Propolis suppresses atopic dermatitis through targeting the MKK4 pathway.

Propolis is a natural resinous substance made by bees through mixing various plant sources. Propolis has been widely recognized as a functional food due to its diverse range of beneficial bioactivities. However, the therapeutic effects of consuming propolis against atopic dermatitis (AD) remain largely unknown. The current study aimed to investigate the potential efficacy of propolis against AD and explore the active compound as well as the direct molecular target. In HaCaT keratinocytes, propolis inhibited TNF-α-induced interleukin (IL)-6 and IL-8 secretion. It also led to a reduction in chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage-derived chemokine (MDC), while restoring the levels of barrier proteins, filaggrin and involucrin. Propolis exhibited similar effects in AD-like human skin, leading to the suppression of AD markers and the restoration of barrier proteins. In DNCB-induced mice, oral administration of propolis attenuated AD symptoms, improved barrier function, and reduced scratching frequency and transepidermal water loss (TEWL). In addition, propolis reversed the mRNA levels of AD-related markers in mouse dorsal skin. These effects were attributed to caffeic acid phenethyl ester (CAPE), the active compound identified by comparing major components of propolis. Mechanistic studies revealed that CAPE as well as propolis could directly and selectively target MKK4. Collectively, these findings demonstrate that propolis may be used as a functional food agent for the treatment of AD.

Coffee and Alzheimer's disease.

Coffee, a universally consumed beverage, is known to contain thousands of bioactive constituents that have garnered interest due to their potential neuroprotective effects against various neurodegenerative disorders, including Alzheimer's disease (AD). Extensive research has been conducted on coffee constituents such as Caffeine, Trigonelline, Chlorogenic acid, and Caffeic acid, focusing on their neuroprotective properties. These compounds have potential to impact key mechanisms in AD development, including amyloidopathy, tauopathy, and neuroinflammation. Furthermore, apart from its neuroprotective effects, coffee consumption has been associated with anticancerogenic and anti-inflammatory effects, thereby enhancing its therapeutic potential. Studies suggest that moderate coffee intake, typically around two to three cups daily, could potentially contribute to mitigating AD progression and lowering the risk of related neurological disorders. This literature underscores the potential neuroprotective properties of coffee compounds, which usually perform their neuronal protective effects via modulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid-derived 2-like 2 (Nrf2), interleukins, tumor necrosis factor-alpha (TNF-α), and many other molecules.

The Influence of Chitosan Derivatives in Combination with Bacillus subtilis Bacteria on the Development of Systemic Resistance in Potato Plants with Viral Infection and Drought.

Viral diseases of potatoes are among the main problems causing deterioration in the quality of tubers and loss of yield. The growth and development of potato plants largely depend on soil moisture. Prevention strategies require comprehensive protection against pathogens and abiotic stresses, including modeling the beneficial microbiome of agroecosystems combining microorganisms and immunostimulants. Chitosan and its derivatives have great potential for use in agricultural engineering due to their ability to induce plant immune responses. The effect of chitosan conjugate with caffeic acid (ChCA) in combination with Bacillus subtilis 47 on the transcriptional activity of PR protein genes and changes in the proteome of potato plants during potato virus Y (PVY) infection and drought was studied. The mechanisms of increasing the resistance of potato plants to PVY and lack of moisture are associated with the activation of transcription of genes encoding PR proteins: the main protective protein (PR-1), chitinase (PR-3), thaumatin-like protein (PR-5), protease inhibitor (PR-6), peroxidase (PR-9), and ribonuclease (PR-10), as well as qualitative and quantitative changes in the plant proteome. The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of combined treatment with B. subtilis and chitosan conjugate indicate that, in potato plants, the formation of resistance to viral infection in drought conditions proceeds synergistically. By two-dimensional electrophoresis of S. tuberosum leaf proteins followed by MALDI-TOF analysis, 10 proteins were identified, the content and composition of which differed depending on the experiment variant. In infected plants treated with ChCA, the synthesis of proteinaceous RNase P 1 and oxygen-evolving enhancer protein 2 was enhanced in conditions of normal humidity, and 20 kDa chaperonin and TMV resistance protein N-like was enhanced in conditions of lack of moisture. The virus coat proteins were detected, which intensively accumulated in the leaves of plants infected with potato Y-virus. ChCA treatment reduced the content of these proteins in the leaves, and in plants treated with ChCA in combination with Bacillus subtilis, viral proteins were not detected at all, both in conditions of normal humidity and lack of moisture, which suggests the promising use of chitosan derivatives in combination with B. subtilis bacteria in the regulation of plant resistance.

A new and highly efficient source of t-resveratrol: Cephalaria Syriaca (L.) Roem. & Schult.

Recently, interest in bioactive plant compounds has increased due to their properties in preventing and treating diseases like cancer and neurodegenerative disorders. In this study, caffeic acid and t-resveratrol were extracted from Cephalaria syriaca seeds using ultrasonic assisted extraction (UAE) and supercritical carbon dioxide (Sc-CO2) extraction methods. Independent variables were temperature (40, 60, 80 °C), pressure (130, 215, and 300 bar), and co-solvent ratio (ethanol v/v (3.0, 6.5, 10.0%)) were selected. While extraction process conditions were optimized using response surface methodology, polyphenols were determined by an HPLC system. As a result of the Sc-CO2 experimental studies, maximum caffeic acid (88.75 ± 1.71 µg/g dw) was obtained at 80 °C, 130 bar, and 10% ethanol conditions and maximum t-resveratrol (2949.45 ± 51.78 µg/g dw) was obtained at 60 °C, 130 bar, and 6.5% ethanol conditions. The results of the UAE method were found to be 76.21 ± 2.40 µg/g dw caffeic acid and 4629 ± 123.2 µg/g dw t-resveratrol.

Caffeic Acid and Cyclen-Based Hydrogel for Synergistic Antibacterial Therapy.

Caffeic acid is a natural product that contains both phenolic and acrylic functional groups and has been widely employed as an alternative drug to combat chronic infections induced by microbes such as bacteria, fungi, and viruses. Several strategies, including derivatization and nanoformulation, have been applied in order to overcome the issues of water insolubility, poor stability, and the bioavailability of caffeic acid. Here, caffeic acid and cyclen-Zn(II) are incorporated into a G4-assembly by using a phenylborate linker to form the mixed supramolecular prodrug GB-CA/Cy-Zn(II) hydrogel. The delivery system is expected to enhance antibacterial and anti-inflammatory properties during the wound healing process through the synergistic effect of caffeic acid and cyclen-Zn(II). The preparation and physicochemical and mechanical properties of the hydrogel were investigated by NMR, CD, TEM, and rheological assays. The typical inflammatory cytokines and in vitro antibacterial experiments indicated that inflammation and infection can be significant suppressed by the hydrogel treatment. An in vivo infected wound model treated by the hydrogel showed rapid wound healing capacity and biosafety. The current work depicts a simple method to prepare a caffeic acid hydrogel carrier, which facilitates synergistic treatment for inflammation and bacterial infections at the wound site.

Boric acid functionalized Fe3O4@CeO2/Tb-MOF as a luminescent nanozyme for fluorescence detection and degradation of caffeic acid.

Caffeic acid (CA) is a natural polyphenol that can have various positive effects on human health. However, its extraction and processing can cause significant ecological issues. Therefore, it is crucial to detect and degrade CA effectively in the environment. In this study, we have developed a multifunctional magnetic luminescent nanozyme, Fe3O4@CeO2/Tb-MOF, which combines peroxidase activity to detect and degrade CA. The fluorescence of the nanozyme was significantly attenuated due to the specific nucleophilic reaction between its boronic acid moiety and the o-diphenol hydroxyl group of CA, energy competition absorption and photo-induced electron transfer (PET) effect. This nanozyme demonstrates a linear detection range from 50 nM to 500 µM and an exceptionally low detection limit of 18.9 nM, along with remarkable selectivity and stability. Moreover, the synergistic catalysis of Fe3O4 and CeO2 within Fe3O4@CeO2/Tb-MOF fosters peroxidase activity, leading to the generation of substantial free radicals catalyzed by H2O2, which ensures the efficient degradation of CA (∼95%). The superparamagnetic property of Fe3O4 further enables the efficient reuse and recycling of the nanozyme. This research provides a novel approach for the concurrent detection and remediation of environmental contaminants.

Caffeic acid ameliorates metabolic dysfunction-associated steatotic liver disease via alleviating oxidative damage and lipid accumulation in hepatocytes through activating Nrf2 via targeting Keap1.

Metabolic-associated steatotic liver disease (MASLD), known as non-alcoholic fatty liver disease (NAFLD) in the past, encompasses a range of liver pathological conditions marked by the excessive lipid accumulation. Consumption of coffee is closely associated with the reduced risk of MASLD. Caffeic acid (CA), a key active ingredient in coffee, exhibits notable hepatoprotective properties. This study aims to investigate the improvement of CA on MASLD and the engaged mechanism. Mice underwent a 12-week high-fat diet (HFD) regimen to induce MASLD, and liver pathology was assessed using hematoxylin-eosin (H&E) and oil red O (ORO) staining. Hepatic inflammation was evaluated by F4/80 and Ly6G immunohistochemistry (IHC) and myeloperoxidase (MPO) measurement. Pathways and transcription factors relevant to MASLD were analyzed by using microarray data from patients' livers. Oxidative damage was evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Co-immunoprecipitation (CoIP), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) were used to validate the binding between CA and its target protein. CA significantly alleviated liver damage, steatosis and inflammatory injury, and reduced the elevated NAFLD activity score (NAS) in HFD-fed mice. Clinical data indicate that fatty acid metabolism and ROS generation are pivotal in MASLD progression. CA increased the expression of fibroblast growth factor 21 (FGF21), FGF receptor 1 (FGFR1) and ß-Klotho (KLB), and promoted fatty acid consumption. Additionally, CA mitigated oxidative stress injury and activated nuclear factor erythroid 2-related factor-2 (Nrf2). In primary hepatocytes isolated from Nrf2 knockout mice, CA's promotion on FGF21 release and inhibition on oxidative stress and lipotoxicity was disappeared. CA could directly bind to kelch-like ECH-associated protein 1 (Keap1) that is an Nrf2 inhibitor protein. This study suggests that CA alleviates MASLD by reducing hepatic lipid accumulation, lipotoxicity and oxidative damage through activating Nrf2 via binding to Keap1.

Inhibition of Cutaneous TRPV3 Channels by Natural Caffeic Acid for the Alleviation of Skin Inflammation.

Natural caffeic acid (CA) and its analogues have been studied for their potential applications in the treatment of various inflammatory and infectious skin diseases. However, the molecular mechanism underlying the effects of the CA remains largely unknown. Here, we report that CA and its two analogues, caffeic acid phenethyl ester (CAPE) and caffeic acid methyl caffeate (CAMC), inhibit TRPV3 currents in their concentration- and structure-dependent manners with IC50 values ranging from 102 to 410 µM. At the single-channel level, CA reduces the channel open probability and open frequency without alteration of unitary conductance. CA selectively inhibits TRPV3 relative to other subtypes of thermo-TRPs, such as TRPA1, TRPV1, TRPV4, and TRPM8. Molecular docking combined with site-specific mutagenesis reveals that a residue T636 in the Pore-loop is critical for CA binding to TRPV3. Further in vivo evaluation shows that CA significantly reverses TRPV3-mediated skin inflammation induced by skin sensitizer carvacrol. Altogether, our findings demonstrate that CA exerts its anti-inflammatory effects by selectively inhibiting TRPV3 through binding to the pocket formed by the Pore-loop and the S6. CA may serve as a lead for further modification and identification of specific TRPV3 channel inhibitors.

Integrated examination of the transcriptome and metabolome of the gene expression response and metabolite accumulation in soybean seeds for seed storability under aging stress.

Soybean quality and production are determined by seed viability. A seed's capacity to sustain germination via dry storage is known as its seed life. Thus, one of the main objectives for breeders is to preserve genetic variety and gather germplasm resources. However, seed quality and germplasm preservation have become significant obstacles. In this study, four artificially simulated aging treatment groups were set for 0, 24, 72, and 120 hours. Following an aging stress treatment, the transcriptome and metabolome data were compared in two soybean lines with notable differences in seed vigor-R31 (aging sensitive) and R80 (aging tolerant). The results showed that 83 (38 upregulated and 45 downregulated), 30 (19 upregulated and 11 downregulated), 90 (52 upregulated and 38 downregulated), and 54 (25 upregulated and 29 downregulated) DEGs were differentially expressed, respectively. A total of 62 (29 upregulated and 33 downregulated), 94 (49 upregulated and 45 downregulated), 91 (53 upregulated and 38 downregulated), and 135 (111 upregulated and 24 downregulated) differential metabolites accumulated. Combining the results of transcriptome and metabolome investigations demonstrated that the difference between R31 and R80 responses to aging stress was caused by genes related to phenylpropanoid metabolism pathway, which is linked to the seed metabolite caffeic acid. According to this study's preliminary findings, the aging-resistant line accumulated more caffeic acid than the aging-sensitive line, which improved its capacity to block lipoxygenase (LOX) activity. An enzyme activity inhibition test was used to demonstrate the effect of caffeic acid. After soaking seeds in 1 mM caffeic acid (a LOX inhibitor) for 6 hours and artificially aging them for 24 hours, the germination rates of the R31 and R80 seeds were enhanced. In conclusion, caffeic acid has been shown to partially mitigate the negative effects of soybean seed aging stress and to improve seed vitality. This finding should serve as a theoretical foundation for future research on the aging mechanism of soybean seeds.

Formulation of Polymeric Micelles to Increase the Solubility and Photostability of Caffeic Acid.

Caffeic acid (CA), a hydrophobic polyphenol with various pharmacological activities, exhibits a low aqueous solubility and sensitivity to light. In order to improve its chemical properties and overcome the limits in its application, the compound was loaded in P123 micelles (MCs) prepared using two polymer concentrations (10 and 20% w/w, MC10 and MC20). The micelles were characterised in terms of the size distribution, zeta potential, drug encapsulation efficiency, rheology, and cumulative drug release. Micellar formulations exhibited sizes in the range of 11.70 and 17.70 nm and a good polydispersion, indicating the formation of relatively small-sized micelles, which is favourable for drug delivery applications. Additionally, the stability and antioxidant profiles of the free CA and the CA loaded in micelles were studied. The results obtained on the free CA showed the formation of photodegradation products endowed with higher DPPH scavenging activity with respect to the pure compound. Instead, it was found that the incorporation of CA into the micelles significantly increased its solubility and decreased the photodegradation rate. Overall, the results indicate the successful formation of P123 micelles loaded with CA, with promising characteristics such as a small size, good encapsulation efficiency, sustained release profile, and improved light stability. These findings suggest the potentiality of these micelles as a delivery system for CA, thus enhancing its bioavailability.