Caffeic acid phenethyl ester attenuates Enterococcus faecalis infection in vivo: antioxidants and NF-κB have a protective role against stomach damage.

The mammalian gastrointestinal tract hosts a significant microbial symbiont community, an intriguing feature of this complex organ system. This study aimed to investigate the anti-inflammatory, antioxidant, and protective effects of caffeic acid phenethyl ester (CAPE) against Enterococcus faecalis infection in the stomach at a dose of 106 CFU in Swiss mice. A total of 30 mice were randomly assigned to three groups of ten mice each. Group I was the negative control, Group II was infected orally with E. faecalis for 18 days, and Group III was infected with E. faecalis and treated with CAPE orally at a daily dose of 4 mg/kg for 18 days. We assessed the antioxidant activities of stomach homogenate and the immunohistochemical expressions of the transcription factor nuclear factor kappa B (NF-κB) and proliferating cell nuclear antigen (PCNA). Histopathological examination was performed on the stomachs of all mice. Group II had decreased levels of antioxidant activity and positive expressions of NF-κB and PCNA. Histological observations revealed an increase in mucosal and glandular thickness compared with Group I. Group III, treated with CAPE, showed a significant increase in antioxidant activities and a significant decrease in NF-κB and PCNA immunoreactivities compared with Group II. In addition, Group III showed restoration of the normal thickness of the non-glandular and glandular parts of the stomach. Our results revealed that E. faecalis infection has damaging effects on the stomach and proved that CAPE has promising protective, anti-inflammatory, and antioxidant effects against E. faecalis. Further studies may investigate the potential therapeutic effects of CAPE against E. faecalis infection.

Antioxidant Scavenging of the Superoxide Radical by Yerba Mate (Ilex paraguariensis) and Black Tea (Camellia sinensis) Plus Caffeic and Chlorogenic Acids, as Shown via DFT and Hydrodynamic Voltammetry.

We describe the antioxidant capability of scavenging the superoxide radical of several tea and yerba mate samples using rotating ring-disk electrochemistry (RRDE). We directly measured superoxide concentrations and detected their decrease upon the addition of an antioxidant to the electrochemical cell. We studied two varieties of yerba mate, two varieties of black tea from Bangladesh, a sample of Pu-erh tea from China, and two components, caffeic acid and chlorogenic acid. All of these plant infusions and components showed strong antioxidant activities, virtually annihilating the available superoxide concentration. Using density functional theory (DFT) calculations, we describe a mechanism of superoxide scavenging via caffeic and chlorogenic acids. Superoxide can initially interact at two sites in these acids: the H4 catechol hydrogen (a) or the acidic proton of the acid (b). For (a), caffeic acid needs an additional π-π superoxide radical, which transfers electron density to the ring and forms a HO2- anion. A second caffeic acid proton and HO2- anion forms H2O2. Chlorogenic acid acts differently, as the initial approach of superoxide to the catechol moiety (a) is enough to form the HO2- anion. After an additional acidic proton of chlorogenic acid is given to HO2-, three well-separated compounds arise: (1) a carboxylate moiety, (2) H2O2, and a (3) chlorogenic acid semiquinone. The latter can capture a second superoxide in a π-π manner, which remains trapped due to the aromatic ring, as for caffeic acid. With enough of both acids and superoxide radicals, the final products are equivalent: H2O2 plus a complex of the type [X-acid-η-O2], X = caffeic, chlorogenic. Chlorogenic acid (b) is described by the following reaction: 2 O2•- + 2 chlorogenic acid → 2 chlorogenic carboxylate + O2 + H2O2, and so, it acts as a non-enzymatic superoxide dismutase (SOD) mimic, as shown via the product formation of O2 plus H2O2, which is limited due to chlorogenic acid consumption. Caffeic acid (b) differs from chlorogenic acid, as there is no acidic proton capture via superoxide. In this case, approaching a second superoxide to the H4 polyphenol moiety forms a HO2- anion and, later, an H2O2 molecule upon the transfer of a second caffeic acid proton.

Salvianolic acid A inhibits pseudorabies virus infection by directly inactivating the virus particle.

BACKGROUND: Pseudorabies virus (PRV), a member of the family Herpesviridae, is responsible for significant economic losses in the pig industry and has recently been associated with human viral encephalitis, leading to severe neurological symptoms post-recovery. Despite the widespread impact of PRV, there are currently no approved effective drugs for treating PRV-related diseases in humans or pigs. Therefore, the exploration and discovery of safe and effective drugs for the prevention and treatment of PRV infection is of paramount importance. PURPOSE: The objective of this study is to screen and identify natural compounds with antiviral activity against PRV. METHODS: First, we used a strain of PRV with green fluorescent protein (PRV-GFP) to screen a natural product chemical library to identify potential antiviral drugs. Next, we assessed the antiviral abilities of salvianolic acid A (SAA) in vitro using virus titer assay, qPCR, and IFA. We investigated the mechanisms of SAA's antiviral activity through viral attachment, internalization, inactivation, and nuclease digestion assay. Finally, we evaluated the efficacy of SAA in inactivating PRV using mice as the experimental subjects. RESULTS: This study screened 206 natural compounds for anti-PRV activity in vitro, resulting in the identification of seven potential antiviral agents. Notably, SAA emerged as a promising candidate with significant anti-PRV activity. The mechanism of action may be that SAA can directly inactivate the virus by disrupting viral envelope. In vivo experiments have shown that pre-incubation of SAA and PRV can effectively inhibit the infectivity and pathogenicity of PRV in mice. CONCLUSION: This study offers valuable insights into the antiviral properties of SAA, potentially informing strategies for controlling PRV epidemics and treating related diseases in both humans and animals.

Potential of kaempferol and caffeic acid to mitigate salinity stress and improving potato growth.

Salinity stress adversely affects plant growth by disrupting water uptake, inducing ion toxicity, initiating osmotic stress, impairing growth, leaf scorching, and reducing crop yield. To mitigate this issue, the application of kaempferol (KP), caffeic acid (CA), and plant growth-promoting rhizobacteria (PGPR) emerges as a promising technology. Kaempferol, a flavonoid, protects plants from oxidative stress, while caffeic acid, a plant-derived compound, promotes growth by regulating physiological processes. PGPR enhances plant health and productivity through growth promotion, nutrient uptake, and stress mitigation, providing a sustainable solution. However, combining these compounds against drought requires further scientific justification. That's why the current study was conducted using 4 treatments, i.e., 0, 20 µM KP, 30 µM CA, and 20 µM KP + 30 µM CA without and with PGPR (Bacillus altitudinis). There were 4 replications following a completely randomized design. Results showed that 20 µM KP + 30 µM CA with PGPR caused significant enhancement in potato stem length (14.32%), shoot root, and leaf dry weight (16.52%, 11.04%, 67.23%), than the control. The enrichment in potato chlorophyll a, b, and total (31.86%, 46.05%, and 35.52%) was observed over the control, validating the potential of 20 µM KP + 30 µM CA + PGPR. Enhancement in shoot N, P, K, and Ca concentration validated the effective functioning of 20 µM KP + 30 µM CA with PGPR evaluated to control. In conclusion, 20 µM KP + 30 µM CA with PGPR is the recommended amendment to alleviate salinity stress in potatoes.

A new strategy of using low-dose caffeic acid carbon nanodots for high resistance to poorly differentiated human papillary thyroid cancer.

Thyroid cancer is one of the most common endocrine malignancies in clinical practice. Traditional surgery and radioactive iodine ablation have poor treatment results for poorly differentiated thyroid cancer, and there is a risk of metastasis and recurrence. In this study, caffeic acid, a natural herbal extract with certain biological activity, has been as precursor to prepare new caffeic acid carbon nanodots via a one-step hydrothermal method. The caffeic acid carbon nanodots retains part of the structure and biological activity of caffeic acid, and have good biocompatibility, water solubility and stability. The construction of the carbon nanodots could effectively improve their bio-absorption rate and the efficacy. In vitro cell experiments showed that low-dose caffeic acid carbon nanodots had a significant inhibitory effect on poorly differentiated papillary thyroid carcinoma BCPAP cells. At low concentrations of 16 µg/mL, the inhibition rate of human thyroid cancer cells BCPAP was ~ 79%. The anti-tumor mechanism was predicted and verified by transcriptome, real-time quantitative PCR and western blot experiments. The caffeic acid carbon nanodots showed to simultaneously downregulate the expression of KRAS, p-BRAF, p-MEK1 and p-ERK1/2, the four continuous key proteins in a MAPK classical signaling pathway. In vivo experiments further confirmed the caffeic acid carbon nanodots could significantly inhibit the tumorigenicity of xenografts in papillary thyroid carcinoma at quite low doses. This piece of work provides a new nanomedicine and therapeutic strategy for highly resistant poorly differentiated papillary thyroid carcinoma.

[Determination of 13 kinds of free and bound phenolic acids in fruits by high-performance liquid chromatography-mass spectrometry].

OBJECTIVE: To establish a high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS) method for detecting 13 kind of free and bound phenolic acids(chlorogenic acid, protocatechuic acid, ferulic acid, p-coumaric acid, gallic acid, gentisic acid, vanillic acid, caffeic acid, syringic acid, sinapic acid, rosmarinic acid, salicylic acid, p-hydroxybenzoic acid) in fruits, and optimize the pre-treatment conditions to meet the detection requirements for phenolic acid content in various types of fruits. METHODS: Free phenolic acids in fruits were extracted using methanol through ultrasonic extraction. Conjugated phenolic acids in the centrifuged residue were released by alkaline hydrolysis and extracted with ethyl acetate. The two extracts were combined, concentrated, and analyzed using HPLC-MS/MS. Separation was achieved using an Agilent ZORBAX SB-C_(18) chromatography column(3.0 mm×100 mm, 3.5 µm), and detection was performed in multiple reaction monitoring(MRM) mode. RESULTS: All 13 standard phenolic acids achieved complete separation within 10 minutes, with linear correlation coefficients greater than 0.998 and detection limits ranging from 0.172 to 3.471 ng/mL. After optimization of the pre-treatment method, the recovery rates of the method for four types of fruits-apples, strawberries, oranges, and peaches-ranged from 80.0% to 119.4%, and the precision were lower than 7.00%(n=6). The result of testing on four categories of twelve types of fruits demonstrated significant variations in the content of phenolic acids among different fruits, and within the same category, the composition of phenolic acids did not exhibit consistency. CONCLUSION: The HPLC-MS/MS method exhibits high sensitivity, precision, and accuracy. It is suitable for the detection of both free and bound phenolic acids in various types of fruits.

Immobilization of laccase on mesoporous metal organic frameworks for efficient cross-coupling of ethyl ferulate.

Laccases act as green catalysts for oxidative cross-coupling of phenolic antioxidnt compounds, but low stability and non-recyclability limit its application. To address that, metal-organic frameworks Cu-BTC and Cr-MOF were synthesized as supports to immobilize the efficient laccase from Cerrena sp. HYB07. The Brunauer-Emmett-Teller surface area of Cu-BTC and Cr-MOF were 1213.2 and 907.1 m2/g, respectively. The two carriers respectively presented pore diameters of 1.2-10 nm and 1.4-12 nm as octahedron, indicating nano-scale mesoporosity. These Cu-BTC and Cr-MOF carriers could adsorb laccase with enzyme loading of 1933.2 and 1564.4 U/g carrier, respectively. The stability and organic solvent tolerance of Cu-BTC-laccase and Cr-MOF-laccase were both obviously improved compared to free laccase. Thermal inactivation kinetics showed that both the two immobilized laccases displayed lower thermal inactivation rate constants. Importantly, the Cu-BTC-laccase and Cr-MOF-laccase both showed much higher activity for cross-coupling of ethyl ferulate than free laccase, which had 2.5-fold higher cross-coupling efficiency than that by free laccase. The ethyl ferulate coupling product was also analyzed by mass spectroscopy and the synthesis pathway of ethyl ferulate dimer was proposed. The cross coupling of ethyl ferulate required the formation of radical intermediates of ethyl ferulate generated by laccase mediated oxidation. This work paved the way for MOFs immobilized laccase for cross coupling of antioxidant phenols.

Blood-responsive mussel-inspired hydrogels for hemostasis, antibacterial action, and wound healing.

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

Coagulopathy-independent injectable catechol-functionalized chitosan shape-memory material to treat non-compressible hemorrhage.

Uncontrolled non-compressible hemorrhage, which is often accompanied by coagulopathy, is a major cause of mortality following traumatic injuries in civilian and military populations. In this study, coagulopathy-independent injectable catechol-modified chitosan (CS-HCA) hemostatic materials featuring rapid shape recovery were fabricated by combining controlled sodium tripolyphosphate-crosslinking with hydrocaffeic acid (HCA) grafting. CS-HCA exhibited robust mechanical strength and rapid blood-triggered shape recovery. Furthermore, CS-HCA demonstrated superior blood-clotting ability, enhanced blood cell adhesion and activation, and greater protein adsorption than commercial hemostatic gauze and Celox. CS-HCA showed enhanced procoagulant and hemostatic capacities in a lethal liver-perforation wound model in rabbits, particularly in heparinized rabbits. CS-HCA is suitable for mass manufacturing and shows promise as a clinically translatable hemostat.

Effect of caffeic acid and cobalt sulfate on potato (Solanum tuberosum L.) plants in the presence and absence of nanoparticles-coated urea.

Potatoes (Solanum tuberosum L.) are a significant food crop cultivated around the world. Caffeic acid (CA) can enhance plant growth by promoting antioxidant activity and stimulating root development, contributing to overall plant health and vigor. Cobalt sulfate (CoSO4) boosts plant growth by promoting nitrogen (N) fixation, healthier root development, and chlorophyll synthesis, enhancing photosynthesis and overall plant health. Nanoparticle-coated urea (NPCU) improves nutrient uptake, promoting plant growth efficiency and reducing environmental impact. This study investigates the effects of combining CA, CoSO4, and NPCU as amendments on potatoes with and without NPCU. Four treatments, control, 20 µM CA, 0.15 mg/L CoSO4, and 20 µM CA + 0.15 mg/L CoSO4 with and without NPCU, were applied in four replications using a completely randomized design. Results demonstrate that the combination of CA + CoSO4 with NPCU led to an increase in potato stem length (~ 6%), shoot dry weight (~ 15%), root dry weight (~ 9%), and leaf dry weight (~ 49%) compared to the control in nutrient stress. There was a significant rise in chlorophyll a (~ 27%), chlorophyll b (~ 37%), and total chlorophyll (~ 28%) over the control under nutrient stress also showed the potential of CA + CoSO4 with NPCU. In conclusion, the findings suggest that applying CA + CoSO4 with NPCU is a strategy for alleviating potato nutrient stress.

Bioaccessible Phenolic Alkyl Esters of Wine Lees Decrease COX-2-Catalyzed Lipid Mediators of Oxidative Stress and Inflammation in a Time-Dependent Manner.

Lipophenols, phenolic compounds esterified with fatty alcohols or fatty acids, provide greater health benefits upon dietary ingestion of plant-based foods than unesterified (poly)phenols. Based on this premise, the present study aimed to demonstrate the role of gastrointestinal enzymes (pepsin, pancreatin, and pancreatic lipase) in releasing alkyl gallates and trans-caffeates from wine lees, providing bioactive compounds with enhanced capacities against oxidative stress (OS) and para-inflammation. The UHPLC-ESI-QqQ-MS/MS-based analysis revealed ethyl gallate and ethyl trans-caffeate as the most prominent compounds (1.675 and 0.872 µg/g dw, respectively), while the bioaccessibility of the derivatives of gallic and caffeic acids was dependent on the alkyl chain properties. The de novo formation of alkyl gallates during gastric and intestinal digestion resulted from intestinal enzyme activity. Moreover, the in vitro capacity of bioaccessible alkyl esters of gallic and trans-caffeic acids to reduce cyclooxygenase-2 concentration and modulate oxilipins related to OS (8-iso-PGF2α) and inflammation (PGF2α and PGE2) was demonstrated in a time-dependent manner. In conclusion, the presence of alkyl esters of gallic and trans-caffeic acids in wine lees and their subsequent formation during digestion of this byproduct emphasize their value as a source of antioxidant and anti-inflammatory compounds, encouraging the consideration of wine lees as a valuable ingredient for health-promoting coproducts.

Dual feedback inhibition of ATP-dependent caffeate activation economizes ATP in caffeate-dependent electron bifurcation.

The acetogen Acetobacterium woodii couples caffeate reduction with ferredoxin reduction and NADH oxidation via electron bifurcation, providing additional reduced ferredoxin for energy conservation and cell synthesis. Caffeate is first activated by an acyl-CoA synthetase (CarB), which ligates CoA to caffeate at the expense of ATP. After caffeoyl-CoA is reduced to hydrocaffeoyl-CoA, the CoA moiety in hydrocaffeoyl-CoA could be recycled for caffeoyl-CoA synthesis by an ATP-independent CoA transferase (CarA) to save energy. However, given that CarA and CarB are co-expressed, it was not well understood how ATP could be saved when both two competitive pathways of caffeate activation are present. Here, we reported a dual feedback inhibition of the CarB-mediated caffeate activation by the intermediate hydrocaffeoyl-CoA and the end-product hydrocaffeate. As the product of CarA, hydrocaffeate inhibited CarB-mediated caffeate activation by serving as another substrate of CarB with hydrocaffeoyl-CoA produced. It effectively competed with caffeate even at a concentration much lower than caffeate. Hydrocaffeoyl-CoA formed in this process can also inhibit CarB-mediated caffeate activation. Thus, the dual feedback inhibition of CarB, together with the faster kinetics of CarA, makes the ATP-independent CarA-mediated CoA loop the major route for caffeoyl-CoA synthesis, further saving ATP in the caffeate-dependent electron-bifurcating pathway. A genetic architecture similar to carABC has been found in other anaerobic bacteria, suggesting that the feedback inhibition of acyl-CoA ligases could be a widely employed strategy for ATP conservation in those pathways requiring substrate activation by CoA. IMPORTANCE: This study reports a dual feedback inhibition of caffeoyl-CoA synthetase by two downstream products, hydrocaffeate and hydrocaffeoyl-CoA. It elucidates how such dual feedback inhibition suppresses ATP-dependent caffeoyl-CoA synthesis, hence making the ATP-independent route the main pathway of caffeate activation. This newly discovered mechanism contributes to our current understanding of ATP conservation during the caffeate-dependent electron-bifurcating pathway in the ecologically important acetogen Acetobacterium woodii. Bioinformatic mining of microbial genomes revealed contiguous genes homologous to carABC within the genomes of other anaerobes from various environments, suggesting this mechanism may be widely used in other CoA-dependent electron-bifurcating pathways.

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.

Caffeic acid derivative MPMCA suppresses osteoclastogenesis and facilitates osteoclast apoptosis: implications for the treatment of bone loss disorders.

Osteoclast activity plays a crucial role in the pathological mechanisms of osteoporosis and bone remodeling. The treatment of these disorders involves the use of pharmacological medicines that work by inhibiting the activity of osteoclasts. Nevertheless, the prevalent and infrequent negative consequences of current antiresorptive and bone anabolic treatments pose significant drawbacks, hence restricting their prolonged administration in patients, particularly those who are elderly and/or suffer from many medical conditions. We are currently in the process of creating a new molecule called N-(4-methoxyphen) methyl caffeamide (MPMCA), which is a derivative of caffeic acid. This compound has shown potential in preventing the production of osteoclasts and causing existing osteoclasts to undergo cell apoptosis. Our investigation discovered that MPMCA hinders osteoclast function via suppressing the MAPK pathways. The expectation is that the findings of this study will stimulate the advancement of a novel approach to treating anti-resorption.

Flow and On-Water Synthesis and Cancer Cell Cytotoxicity of Caffeic Acid Phenethyl Amide (CAPA) Derivatives.

Caffeic acid phenethyl ester (CAPE) is a phenolic natural product with a wide range of biological activities, including anticancer activity; however, the ester group of CAPE is metabolically labile. The corresponding amide, CAPA, has improved metabolic stability but limited anticancer activity relative to CAPE. We report the synthesis using flow and on-water Wittig reaction approaches of five previously reported and five novel CAPA analogues. All of these analogues lack the reactive catechol functionality of CAPA and CAPE. Cytotoxicity studies of CAPE, CAPA, and these CAPA analogues in HeLa and BE(2)-C cells were carried out. Surprisingly, we found that CAPA is cytotoxic against the neuroblastoma BE(2)-C cell line (IC50 = 12 µM), in contrast to the weak activity of CAPA against HeLa cells (IC50 = 112 µM), and the literature reports of the absence of activity for CAPA against a variety of other cancer cell lines. One novel CAPA analogue, 3f, was identified as having cytotoxic activity similar to CAPE in HeLa cells (IC50 = 63 µM for 3f vs. 32 µM for CAPE), albeit with lower activity against BE(2)-C cells (IC50 = 91 µM) than CAPA. A different CAPA analogue, 3g, was found to have similar effects against BE(2)-C cells (IC50 = 92 µM). These results show that CAPA is uniquely active against neuroblastoma cells and that specific CAPA analogues that are predicted to be more metabolically stable than CAPE can reproduce CAPA's activity against neuroblastoma cells and CAPE's activity against HeLa cells.

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.

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.

Targeting post-stroke neuroinflammation with Salvianolic acid A: molecular mechanisms and preclinical evidence.

Salvianolic acid A (SalA), a bioactive compound extracted from Salvia miltiorrhiza, has garnered considerable interest for its potential in ameliorating the post-stroke neuroinflammation. This review delineates the possible molecular underpinnings of anti-inflammatory and neuroprotective roles of SalA, offering a comprehensive analysis of its therapeutic efficacy in preclinical studies of ischemic stroke. We explore the intricate interplay between post-stroke neuroinflammation and the modulatory effects of SalA on pro-inflammatory cytokines, inflammatory signaling pathways, the peripheral immune cell infiltration through blood-brain barrier disruption, and endothelial cell function. The pharmacokinetic profiles of SalA in the context of stroke, characterized by enhanced cerebral penetration post-ischemia, makes it particularly suitable as a therapeutic agent. Preliminary clinical findings have demonstrated that salvianolic acids (SA) has a positive impact on cerebral perfusion and neurological deficits in stroke patients, warranting further investigation. This review emphasizes SalA as a potential anti-inflammatory agent for the advancement of innovative therapeutic approaches in the treatment of ischemic stroke.

Addition of Mucoadhesive Agent to Enzymatically Polymerized Caffeic Acid-Based Nasal Vaccine Formulation Attenuates Antigen-Specific Antibody Responses in Mice.

Mucosal vaccination is a promising strategy for combating infectious diseases caused by pathogenic microbes, as it can generate antigen-specific immune responses in both systemic and mucosal compartments. In our recent study, we developed a nasal vaccine system for Streptococcus pneumoniae infections in mice using enzymatically polymerized polyphenols such as caffeic acid. However, the efficacy of this mucosal vaccine system is approximately 70%, indicating a need for improvement. To address this issue, we hypothesized that incorporating a mucoadhesive agent that enhances mucosal absorption into a polyphenol-based mucosal vaccine system would improve vaccine efficacy. Contrary to our expectations, we found that adding a mucoadhesive agent, hydrophobically modified hydroxypropylmethylcellulose, to the vaccine system reduced the stimulation of antigen-specific antibody responses in both the mucosal (more than 90% reduction; P < 0.05) and systemic compartments (more than 80% reduction; P < 0.05). Although the addition of the mucoadhesive agent may have interfered with the interaction between the mucosal epithelium and the vaccine system, the underlying mechanism remains unclear, and further research is needed to fully understand the mechanisms involved.

Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways.

Propolis is a natural product used in cancer treatment, which is produced by bees via different sources. The chemical composition of Propolis is determined based on the climatic and geographical conditions, as well as harvesting time and method. This compound has been the subject of numerous investigational endeavors due to its expansive therapeutic capacity which includes antibacterial, anti-fungal, anti-inflammatory, anti-oxidant, anti-viral, and anti-cancer effects. The growing incidence rate of different cancers necessitates the need for developing novel preventive and therapeutic strategies. Chemotherapy, radiotherapy, and stem cell therapy have proved effective in cancer treatment, regardless of the adverse events associated with these modalities. Clinical application of natural compounds such as Propolis may confer promise as an adjuvant therapeutic intervention, particularly in certain subpopulations of patients that develop adverse events associated with anticancer regimens. The diverse biologically active compounds of propolis are believed to confer anti-cancer potential by modulation of critical signaling cascades such as caffeic acid phenethyl ester, Galangin, Artepillin C, Chrysin, Quercetin, Caffeic acid, Nymphaeols A and C, Frondoside A, Genistein, p-coumaric acid, and Propolin C. This review article aims to deliver a mechanistic account of anti-cancer effects of propolis and its components. Propolis can prevent angiogenesis by downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB, while counteracting metastatic progression of cancer by inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways. Moreover, propolis or its main components show regulatory effects on cyclin D, CDK2/4/6, and their inhibitors. Additionally, propolis-induced up-regulation of p21 and p27 may result in cell cycle arrest at G2/M or G0/G1. The broad anti-apoptotic effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling pathway. Considering the growing body of evidence regarding different anti-cancers effects of propolis and its active components, this natural compound could be considered an effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy.