RESUMEN

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.

Asunto(s)

Catecoles , Quitosano , Hemorragia , Hemostáticos , Quitosano/química , Quitosano/farmacología , Animales , Conejos , Catecoles/química , Catecoles/farmacología , Hemorragia/tratamiento farmacológico , Hemostáticos/química , Hemostáticos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Masculino , Materiales Inteligentes/química , Inyecciones

RESUMEN

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.

Asunto(s)

Ácidos Cafeicos , Nanopartículas , Solanum tuberosum , Urea , Solanum tuberosum/efectos de los fármacos , Solanum tuberosum/crecimiento & desarrollo , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química , Urea/farmacología , Nanopartículas/química , Cobalto/farmacología , Cobalto/química , Fotosíntesis/efectos de los fármacos , Clorofila/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Hojas de la Planta/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Ácidos Cafeicos , Enzimas Inmovilizadas , Lacasa , Estructuras Metalorgánicas , Lacasa/química , Lacasa/metabolismo , Estructuras Metalorgánicas/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Estabilidad de Enzimas , Cobre/química , Porosidad , Cinética , Cromo/química , Adsorción , Oxidación-Reducción , Antioxidantes/química

RESUMEN

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.

Asunto(s)

Antioxidantes , Ácidos Cafeicos , Camellia sinensis , Ácido Clorogénico , Ilex paraguariensis , Superóxidos , Superóxidos/química , Superóxidos/metabolismo , Ácidos Cafeicos/química , Ácido Clorogénico/química , Ilex paraguariensis/química , Antioxidantes/química , Camellia sinensis/química , Teoría Funcional de la Densidad , Depuradores de Radicales Libres/química , Técnicas Electroquímicas , Extractos Vegetales/química

RESUMEN

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.

Asunto(s)

Antibacterianos , Bivalvos , Hemostasis , Hidrogeles , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Ratones , Bivalvos/química , Antibacterianos/farmacología , Antibacterianos/química , Quitosano/química , Quitosano/farmacología , Porcinos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Celulosa/química , Celulosa/farmacología , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química

RESUMEN

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.

Asunto(s)

Ciclooxigenasa 2 , Ésteres , Estrés Oxidativo , Fenoles , Vino , Estrés Oxidativo/efectos de los fármacos , Vino/análisis , Fenoles/química , Fenoles/metabolismo , Ésteres/química , Ésteres/metabolismo , Ciclooxigenasa 2/metabolismo , Humanos , Inflamación/metabolismo , Vitis/química , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo

RESUMEN

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.

Asunto(s)

Antineoplásicos , Ácidos Cafeicos , Alcohol Feniletílico , Humanos , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química , Ácidos Cafeicos/síntesis química , Células HeLa , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/química , Alcohol Feniletílico/síntesis química , Agua/química , Línea Celular Tumoral , Amidas/farmacología , Amidas/química , Supervivencia Celular/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Técnicas Biosensibles , Ácidos Cafeicos , Cerio , Límite de Detección , Ácidos Cafeicos/química , Ácidos Cafeicos/análisis , Técnicas Biosensibles/métodos , Cerio/química , Estructuras Metalorgánicas/química , Terbio/química , Ácidos Borónicos/química , Espectrometría de Fluorescencia/métodos , Peróxido de Hidrógeno/química , Fluorescencia , Ácidos Bóricos

RESUMEN

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.

Asunto(s)

Antioxidantes , Própolis , Espectrometría de Masas en Tándem , Própolis/química , Antioxidantes/química , Ácidos Cafeicos/química , Ácidos Cafeicos/análisis , Flavonoides/química , Flavonoides/análisis , Estructura Molecular , Cromatografía Liquida/métodos , Cromatografía Líquida de Alta Presión

RESUMEN

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.

Asunto(s)

Ácidos Cafeicos , Carbono , Técnicas Electroquímicas , Molibdeno , Nanosferas , Té , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Té/química , Técnicas Electroquímicas/instrumentación , Nanosferas/química , Carbono/química , Molibdeno/química , Límite de Detección , Contaminación de Alimentos/análisis , Camellia sinensis/química

RESUMEN

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.

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Our study focuses on a major issue affecting young animals. After weaning, piglets are particularly vulnerable to severe intestinal infections due to their immature intestinal systems, leading to damaged barriers and financial losses for the pig industry. We explore the possibility of using caffeic acid (CA), a natural compound found in plants, to promote intestinal health. Our research shows that adding CA to the diet can reduce intestinal inflammation and improve barrier function in weaned piglets challenged by lipopolysaccharide. CA positively affects ileal microbiota by increasing beneficial bacteria like Lactobacillus and Terrisporobacter and decreasing Romboutsia. We also observed differing regulatory effects of CA between the ileum and colon, with opposite changes in primary bile acids. Our findings emphasize the potential of CA as a dietary supplement to improve intestinal barrier function and modulate the inflammatory response by targeting gut microbiota and metabolites. To our knowledge, this is the first to demonstrate the effects of CA on ileal barrier function and microbiota in piglets. Our findings could significantly benefit the pig industry by mitigating financial losses from serious intestinal infections. Additionally, this research may offer key insights into the health of human infants' intestines.

Asunto(s)

Ácidos Cafeicos , Microbioma Gastrointestinal , Lipopolisacáridos , Animales , Lipopolisacáridos/farmacología , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Porcinos , Dieta/veterinaria , Inflamación/veterinaria , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/microbiología , Intestinos/efectos de los fármacos , Intestinos/microbiología , Masculino , Alimentación Animal/análisis

RESUMEN

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.

Asunto(s)

Apoptosis , Ácidos Cafeicos , Osteoclastos , Osteogénesis , Ácidos Cafeicos/farmacología , Osteogénesis/efectos de los fármacos , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Resorción Ósea/terapia , Células RAW 264.7 , Animales , Ratones , Línea Celular , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo

RESUMEN

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.

Asunto(s)

Ácidos Cafeicos , Simulación del Acoplamiento Molecular , Canales Catiónicos TRPV , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/antagonistas & inhibidores , Humanos , Animales , Ratones , Piel/metabolismo , Piel/efectos de los fármacos , Piel/patología , Cimenos/farmacología , Cimenos/química , Células HEK293 , Antiinflamatorios/farmacología , Antiinflamatorios/química , Inflamación/tratamiento farmacológico , Inflamación/metabolismo

RESUMEN

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.

Asunto(s)

Neoplasias , Própolis , Transducción de Señal , Própolis/farmacología , Própolis/química , Própolis/uso terapéutico , Humanos , Transducción de Señal/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/uso terapéutico , Ácidos Cafeicos/química , Alcohol Feniletílico/análogos & derivados , Fenilpropionatos

RESUMEN

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.

Asunto(s)

Administración Intranasal , Ácidos Cafeicos , Animales , Ácidos Cafeicos/administración & dosificación , Ácidos Cafeicos/farmacología , Ratones , Ratones Endogámicos BALB C , Femenino , Inmunidad Mucosa/efectos de los fármacos , Formación de Anticuerpos/efectos de los fármacos , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/inmunología

RESUMEN

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.

Asunto(s)

Antiinflamatorios , Ácidos Cafeicos , Enfermedades Neuroinflamatorias , Accidente Cerebrovascular , Humanos , Animales , Ácidos Cafeicos/uso terapéutico , Ácidos Cafeicos/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/etiología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Lactatos/uso terapéutico , Lactatos/farmacología , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos

RESUMEN

Iron-anchored nitrogen/doped carbon single-atom nanozymes (Fe-N/C), which possess homogeneous active sites and adjustable catalytic environment, represent an exemplary model for investigating the structure-function relationship and catalytic activity. However, the development of pyrolysis-free synthesis technique for Fe-N/C with adjustable enzyme-mimicking activity still presents a significant challenge. Herein, Fe-N/C anchored three carrier morphologies were created via a pyrolysis-free approach by covalent organic polymers. The peroxidase-like activity of these Fe-N/C nanozymes was regulated via the pores of the anchored carrier, resulting in varying electron transfer efficiency due to disparities in contact efficacy between substrates and catalytic sites within diverse microenvironments. Additionally, a colorimetric sensor array for identifying antioxidants was developed: (1) the Fe-N/C catalytically oxidized two substrates TMB and ABTS, respectively; (2) the development of a colorimetric sensor array utilizing oxTMB and oxABTS as sensing channels enabled accurate discrimination of antioxidants such as ascorbic acid (AsA), glutathione (GSH), cysteine (Cys), gallic acid (GA), and caffeic acid (CA). Subsequently, the sensor array underwent rigorous testing to validate its performance, including assessment of antioxidant mixtures and individual antioxidants at varying concentrations, as well as target antioxidants and interfering substances. In general, the present study offered valuable insights into the active origin and rational design of nanozyme materials, and highlighting their potential applications in food analysis.

Asunto(s)

Antioxidantes , Carbono , Colorimetría , Hierro , Nitrógeno , Colorimetría/métodos , Antioxidantes/análisis , Antioxidantes/química , Nitrógeno/química , Hierro/química , Hierro/análisis , Carbono/química , Ácido Gálico/química , Ácido Gálico/análisis , Catálisis , Bencidinas/química , Ácido Ascórbico/análisis , Ácido Ascórbico/química , Nanoestructuras/química , Benzotiazoles/química , Glutatión/análisis , Glutatión/química , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Cisteína/análisis , Cisteína/química , Ácidos Sulfónicos/química , Oxidación-Reducción

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. AIM OF THE STUDY: The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. MATERIALS AND METHODS: This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1ß, TNF-α, IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. RESULTS: A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1ß, TNF-α, IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro. Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. CONCLUSION: The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.

Asunto(s)

Medicamentos Herbarios Chinos , Absorción Intestinal , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratas , Absorción Intestinal/efectos de los fármacos , Administración Oral , Ácidos Cafeicos/farmacocinética , Ácidos Cafeicos/administración & dosificación , Factores de Edad

RESUMEN

Triple-negative breast cancer (TNBC) still one of the most challenging sub-type in breast cancer clinical. Caffeic acid (CA) derived from effective components of traditional Chinese herbal medicine has been show potential against TNBCs. Our research has found that CA can inhibit the proliferation of TNBC cells while also suppressing the size of cancer stem cell spheres. Additionally, it reduces reactive oxygen species (ROS) levels and disruption of mitochondrial membrane potential. Simultaneously, CA influences the stemness of TNBC cells by reducing the expression of the stem cell marker protein CD44. Furthermore, we have observed that CA can modulate the FOXO1/FIS signaling pathway, disrupting mitochondrial function, inducing mitochondrial autophagy, and exerting anti-tumor activity. Additionally, changes in the immune microenvironment were detected using a mass cytometer, we found that CA can induce M1 polarization of macrophages, enhancing anti-tumor immune responses to exert anti-tumor activity. In summary, CA can be considered as a lead compound for further research in targeting TNBC.

Asunto(s)

Ácidos Cafeicos , Proliferación Celular , Transducción de Señal , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Autofagia/efectos de los fármacos , Ácidos Cafeicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proteína Forkhead Box O1/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente Tumoral/efectos de los fármacos

RESUMEN

The histone deacetylase 2 (HDAC2), an enzyme involved in gene regulation, is a potent drug target for the treatment of colon cancer. Phytocompounds having anticancer properties show the ability to interact with HDAC2 enzyme. Among the compounds, docking scores of caffeic acid (CA) and p-coumaric acid (pCA) with HDAC2 showed good binding efficacy of -5.46 kcal/mol and -5.16 kcal/mol, respectively, with small inhibition constants. The higher binding efficacy of CA compared to pCA can be credited to the presence of an extra oxygen atom in the CA molecule, which forms an additional hydrogen bond with Tyr297. The HDAC2 in complex with these molecules was found to be stable by analyzing RMSD, RMSF, Rg, and SASA values obtained through MD simulations. Furthermore, CA and pCA exhibited low MM/GBSA free energies of -16.32 ± 2.62 kcal/mol and -17.01 ± 2.87 kcal/mol, respectively. The HOMO and LUMO energy gaps, dipole moments, global reactivity descriptor values, and MEP surfaces showed the reactivity of the molecules. The favourable physicochemical and pharmacokinetic properties, along with absence of toxicity of the molecules determined using ADMET analysis, suggested both the acids to be regarded as effective drugs in the treatment of colon cancer.

Asunto(s)

Neoplasias del Colon , Histona Desacetilasa 2 , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Humanos , Histona Desacetilasa 2/antagonistas & inhibidores , Histona Desacetilasa 2/metabolismo , Histona Desacetilasa 2/química , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Propionatos/química , Propionatos/farmacología , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacología , Enlace de Hidrógeno , Teoría Funcional de la Densidad