Polyphenols Research Articles

Recent advances in physical/chemical methods as alternatives to SO2 for winemaking: Principles, challenges and perspectives

Sulphur dioxide (SO2) is commonly used in the wine industry to prevent oxidation and maintain microbial stability. However, it can harm consumer health, resulting in a growing demand for chemical-free wine. Therefore, reducing or eliminating the addition of SO2 has become a prevalent trend in the wine industry. In recent years, researchers have made significant progress in finding alternative methods to SO2. This review provides the latest research progress on innovative methods proposed to replace SO2 in winemaking. These include dimethyl dicarbonate, silver nanoparticles, lysozyme, chitosan, phenolic compounds, membrane filtration, ultrasound, ultraviolet irradiation, high pressure, and pulsed electric field. However, these individual antimicrobial methods do not possess the same comprehensive antimicrobial and antioxidant properties as SO2. In the proposed strategy, a promising alternative to SO2 could be to combine physical sterilization technologies with antimicrobial substances. In particular, gentle physical techniques such as pulsed electric field in synergy with natural grape polyphenols can maintain the microbiological stability of wine without the introduction of foreign aid substances, while enhancing the wine's antioxidant properties. In conclusion, while replacing SO2 entirely for wine production remains challenging, the combination of physical sterilization technologies and natural antimicrobial substances shows promise as a viable alternative.

Unveiling the antibacterial potential of anthocyanins - a comprehensive review on this natural plant extract.

With the gradual prohibition of antibiotic fungicides, it is of great significance to develop high-efficient, nontoxic and environmental-friendly antimicrobial agents. Anthocyanin is a natural plant polyphenol pigment which shows antibacterial, anti-inflammatory and antioxidant effects through inhibiting the synthesis of bacterial cell wall, interfering bacterial respiratory metabolism, and inducing bacterial autolysis. As a typical antibacterial agent, anthocyanins have been widely used in various fields, including biological pesticides or feed additives in agricultural production, anti-inflammatory and antibacterial wound dressings in medicine, etc. However, the structure of anthocyanins is unstable, which limits its practical application. In this article, the biological activity, antibacterial mechanism and stabilization strategy of anthocyanins as antibacterial agents were reviewed. The safety, application scope and methods of anthocyanins were discussed. In addition, the challenges and development prospects of anthocyanin extract antibacterial technology were also prospected. This will be the direction for researchers to further explore and better apply anthocyanins to practical production and application.

Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin

AbstractDiabetes mellitus is a chronic metabolic disorder affecting millions of people worldwide and causes serious complications such as diabetic nephropathy. Curcumin, a natural polyphenol derived from turmeric, has demonstrated antidiabetic, anti‐inflammatory, and antioxidant properties. However, the molecular mechanisms underlying curcumin's anti‐diabetic effects remain incompletely understood. This study employed network pharmacology, molecular docking, and simulation techniques to explore the potential targets, and key pathways of curcumin in the treatment of diabetes. Using SwissTarget prediction and Superpred databases, we predicted the molecular targets for curcumin, while diabetes‐associated genes were obtained from DisGeNet. We identified 60 common targets for curcumin in diabetes. Protein‐protein interaction (PPI) analysis revealed three sub‐networks and ten hub genes with AKT1, TNF‐α, EGFR, and STAT3 identified as key hub genes that could serve as potential biomarkers. Gene enrichment analysis indicated that these genes primarily regulate insulin resistance and other metabolic pathways. Quantum‐polarized ligand docking (QPLD) showed that curcumin establishes multiple hydrogen and hydrophobic interactions with the essential amino acids of these hub targets. Molecular simulation results demonstrated stable dynamic behavior, a compact structure, and variations in residue flexibility. Binding free energy calculations using MM/GBSA and MM/PBSA methods validate curcumin's strong binding to the potential targets. Total binding free energy using MM/GBSA ranged from −21.35 to −30.94 kcal/mol while MM/PBSA calculations showed total binding free energy values between −19.80 and −26.66 kcal/mol. Altogether, this study provides valuable insights into the molecular targets of curcumin in diabetes and lays the foundation for future advancements in diabetes treatment.

Extraction, Purification and Characterization of Poly Phenol Oxidase from Potato and Apple and Inhibition of Enzymatic Browning

The purpose of this study was to determine the optimum conditions for the extraction of polyphenol oxidase (PPO) from potato and apple. PPO is found in a variety of fruits and vegetables and is the enzyme that causes browning reactions when handling damaged cells. At 405 nm, the enzyme activity was determined using spectrophotometry. PPO was researched to stop potato and apple from browning, which reduces their marketability. The outcomes showed that using an extraction buffer containing phosphate buffer (0.05 M, pH 6.6) was the optimum condition for the extraction of polyphenol oxidase from potato and apple. In addition, the results showed that as the temperature increased, the (PPO) activity increased, and the activity reached its peak at a temperature of 35 ͦC. The optimum pH value of (PPO) activity was 6.5 and we observed during the research that (PPO) decreased in strong acid condition and alkaline environments. Moreover, the results showed that the highest activity of polyphenol oxidase enzyme extracted from apple and potato was by using (O-dihydroxybenzene) as a substrate. As the concentration of the substrate increased, the (PPO) activity increased, reaching the optimum substrate concentration of 0.8%, and then its activity decreased. Also, we found that when using ascorbic acid, citric acid, and Na2SO3 as inhibitors, the activity of the polyphenol oxidase enzyme decreased with an increase in the concentration of ascorbic acid, citric acid, and Na2SO3. Sodium thiosulfate, 0.01 M ascorbic acid and 0.5% polyethylene glycol were extracted with an extraction ratio of 1:4 (w/v) for three minutes by using a blender. The purpose of study was to determine the optimum conditions for polyphenol oxidase extraction from potato and apple.

A glutathione-activated bismuth-gallic acid metal-organic framework nano-prodrug for enhanced sonodynamic therapy of breast tumor

Sonodynamic therapy is a promising, noninvasive, and precise tumor treatment that leverages sonosensitizers to generate cytotoxic reactive oxygen species during ultrasound stimulation. Gallic acid (GA), a natural polyphenol, possesses certain anti-tumor properties, but exhibits significant toxicity toward normal cells, limiting its application in cancer treatment. To overcome this issue, we synthesized a bismuth-gallic acid (BGA), coordinated metal–organic framework (MOF) nano-prodrug. Upon encountering glutathione (GSH), BGA gradually dissociated and depleted GSH, releasing GA, which had anti-tumor effects. As an MOF with semiconductor properties, BGA primarily produced superoxide anion radical upon ultrasound excitation. After the release of GA, GA generated superoxide anion radical and further produced high toxic singlet oxygen under ultrasound stimulation, while further oxidizing and consuming GSH, enhancing sonocatalytic performance. Additionally, the released GA induced cell cycle arrest, ultimately leading to apoptosis. Our results revealed that BGA, as a GSH-activated, metal-polyphenol MOF nano-prodrug, showed potential for use in breast tumor sonodynamic therapy, providing a novel strategy for precise tumor treatment.

Polyphenol-Based Self-Assembled Nanomedicine for a Three-Pronged Approach to Reversing Tumor Immunosuppression.

The challenges of multi-pathway immune resistance and systemic toxicity caused by the direct injection of immune checkpoint inhibitors are critical factors that compromise the effectiveness of clinical immune checkpoint blockade therapy. In this context, natural polyphenols have been employed as the primary component to construct a targeted and acid-responsive PD-L1 antibody (αPD-L1) delivery nanoplatform. This platform incorporates garcinol, an inhibitor of the Nuclear Factor Kappa-B (NF-κB) signaling pathway, to regulate pro-tumor immune escape cytokines and regulatory T cells. Additionally, the nanoplatform has been verified to induce immunogenic cell death (ICD), which promotes the maturation of dendritic cells and enhances the activity of cytotoxic T lymphocytes. In vivo and in vitro experimental results demonstrated that the nanoplatform can boost the immune response through a PD-L1 and NF-κB blocking/ICD inducing three-pronged strategy, thereby effectively combating tumor growth and metastasis.

The Inhibitory Effects of the Natural Stilbene Piceatannol on Lactate Transport In Vitro Mediated by Monocarboxylate Transporters.

Lactate, a signaling molecule and energy source, crosses membranes through monocarboxylate transporters (MCTs). MCT1 and MCT4 are potential cancer drug targets due to their role in metabolic reprogramming of cancer cells. Stilbenes, plant secondary metabolites found in several food sources, have anticancer effects, though their mechanisms of action are not well understood. This study links the anticancer activity of natural stilbenes to tumor cell lactate metabolism. The impact of resveratrol, pinostilbene, pterostilbene, rhapontigenin, and piceatannol on lactate transport is studied using a fluorescence resonance energy transfer (FRET)-based lactate sensor. The viability and migration of cells expressing MCT1 or MCT4 are also evaluated. Piceatannol inhibits MCT1 effectively at low micromolar concentrations, with less effect on MCT4. All stilbenes significantly reduce cell viability and migration. These findings indicate that both MCTs are stilbene targets, with piceatannol highlighted as a cost-effective, low-toxicity compound for studying MCTs in cancer, providing a new mechanism of action of the therapeutic and nutraceutical effects of natural polyphenols. This enriches the understanding of dietary polyphenols in cancer prevention and therapy.

GSH responsive AuNRs@TFF nanotheranostic for NIR-II photoacoustic imaging-guided CDT/PTT synergistic cancer therapy

Gold nanorods (AuNRs) are important photothermal therapeutic agents; however, a single therapy does not achieve satisfactory outcomes, and the synthesis process often leads to the adsorption of cetyltrimethylammonium bromide on the surface of AuNRs, which reduces its biocompatibility. Natural polyphenols are abundant in natural plants and have good biocompatibility. The metal-polyphenol network is formed by the coordination of metal ions and polyphenols, which has good drug loading, surface adhesion, and biocompatibility. In this study, the metal-polyphenol network structure formed by a transition metal (iron) and natural polyphenol tannic acid was used to modify the surface of gold nanorods (AuNRs@TF). Additionally, the surfaces of AuNRs were modified using the targeted functional molecule mercapto folic acid (AuNRs@TFF). The constructed composite nanomaterials AuNRs@TFF has good biocompatibility and tumor targeting ability. Tannic acid‑iron degrades in the tumor microenvironment and releases iron ions that catalyze the Fenton reaction, thereby facilitating chemodynamic therapy. The good photo-thermal ability of AuNRs generate good photoacoustic signals to facilitate photoacoustic imaging mediation and enhances photothermal and chemodynamic therapy performance. This study expands on the application of AuNRs in the field of nanomedicine. The simple and effective design of AuNRs@TFF provides a strategy for the development of synergistic therapeutic agents for photothermal therapy and chemodynamic therapy.

Reversal of neurodevelopmental impairment and cognitive enhancement by pharmacological intervention with the polyphenol polydatin in a Down syndrome model

Intellectual disability (ID) is the unavoidable hallmark of Down syndrome (DS), a genetic condition due to triplication of chromosome 21. ID in DS is largely attributable to neurogenesis and dendritogenesis alterations taking place in the prenatal/neonatal period, the most critical time window for brain development. There are currently no treatments for ID in DS. Considering the timeline of brain development, treatment aimed at improving the neurological phenotypes of DS should be initiated as early as possible and use safe agents. The goal of this study was to establish whether it is possible to improve DS-linked neurodevelopmental defects through early treatment with polydatin, a natural polyphenol. We used the Ts65Dn mouse model of DS and focused on the hippocampus, a brain region fundamental for long-term memory. We found that in Ts65Dn mice of both sexes treated with polydatin from postnatal (P) day 3 to P15 there was full restoration of neurogenesis, neuron number, and dendritic development. These effects were accompanied by normalization of Cyclin D1 and DSCAM levels, which may account for the rescue of neurogenesis and dendritogenesis, respectively. Importantly, in Ts65Dn mice treated with polydatin from P3 to adolescence (∼P50) there was full restoration of hippocampus-dependent memory, indicating a pro-cognitive outcome of treatment. No adverse effects were observed on the body and brain weight. The efficacy and safety of polydatin in a model of DS prospect the possibility of its use during early life stages for amelioration of DS-linked neurodevelopmental alterations.

Carob pulp flour as an innovative source of bioactive molecules for the preparation of high-value-added jellies

The rising demand for healthier alternatives to traditional sugary products has driven the exploration of natural substitutes for sucrose. This study aimed to investigate carob pulp flour (CPF) as a viable alternative to sucrose in the production of high-value jellies with enhanced health benefits. Carob pulp flour was spectroscopically characterized, revealing the presence of bioactive molecules, such as natural antidiabetic polyols and polyphenols. Colorimetric tests demonstrated a significant concentration of polyphenolic molecules in CPF, with a remarkable scavenging activity against radical species in both organic and aqueous environments. Jellies based on CPF (CGC) were successfully prepared and exhibited strong antioxidant activity against ABTS (IC50 0.158 mg mL−1) and DPPH (IC50 0.175 mg mL−1) radicals, maintaining their properties over 15 days, unlike the sucrose-based control, which showed no antioxidant activity. The CPF-enhanced jellies consistently demonstrated higher G′ values (in the range 20–35 °C) than the sucrose-based jellies, indicating improved consistency, elasticity, and strong gel properties, even at higher temperatures. Sensory analysis revealed significant differences, with CPF-based jellies displaying enhanced chocolate (2.3 ± 1.0), ripe fruit (2.3 ± 1.8), and caramel odors (2.0 ± 0.9), as well as increased bitterness and astringency, reduced sweetness, and improved texture. Additionally, CPF-based jellies exhibited significant hypoglycemic properties, with dose-dependent inhibitory effects on α-amylase (57.7 %) and α-glucosidase (50.3 %), and a moderate lipase inhibitory effect (48.6 %) at the maximum concentrations tested. The findings of this study highlight the potential of CPF as a functional ingredient in the food industry, offering a healthier alternative to sucrose in jelly production. The inclusion of CPF not only enhances the antioxidant and sensory properties of jellies but also contributes to significant hypoglycemic effects, making it a promising candidate for the development of functional foods with added health benefits.

Ultrasound-assisted extraction of polyphenols from Phyllanthi Fructus: Comprehensive insights from extraction optimization and antioxidant activity

Phyllanthi Fructus (PF) is a valuable botanical resource with a long history of traditional use, known for potent antioxidant and anti-inflammatory effects attributed to its rich contents of bioactive compounds, particularly polyphenols. However, current extraction techniques limit the utilization of polyphenols from PF. This study aimed to achieve the maximum polyphenol yield and improve the antioxidant activity of PF extracts to promise PF’s prospects for modern healthcare.Firstly, ultrasonic-assisted extraction (UAE) was employed to extract the polyphenols in PF and a combination of Plackett-Burman designs (PBD) and response surface methodology (RSM) was applied to optimize UAE’s conditions. Next, cellular superoxide dismutase (SOD) and malondialdehyde (MDA) were used to assess the antioxidant activity of extracted polyphenols. Ultra-Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF MS) was utilized to characterize polyphenol components in the PF extracts. Finally, network pharmacology and molecular docking analysis were performed to screen the potential target proteins of polyphenols from PF.As a result, the optimized polyphenol yield was 213.49 mg/g, and the antioxidant activities, measured by ability of DPPH scavenging, ABTS+ scavenging, and FRAP were 76.95 %, 2.24 mmol/g, 2.34 mmol/g, respectively. PF extracts also showed good antioxidant capabilities at cellular level. 26 polyphenol components were identified in the PF extracts. Among these, ellagic acid, myricetin, and eriodictyol may exert antioxidant effects by interacting with AKT serine/threonine kinase 1 (AKT1).In conclusion, our study provides valuable insights into the optimizing PF extraction and underscores its potential applications in enhancing natural polyphenols extraction using UAE with a combination of PBD and RSM. These findings offer a promising avenue for the development and utilization of PF, and could serve as a reference for similar extraction processes in the future.

Osmundacetone ameliorates Alzheimer's-like pathologies by inhibiting β-amyloid fibrillation, oxidative damage and neuroinflammation in APP/PS1 transgenic mice

Backgroundβ-Amyloid (Aβ) fibrillation is critical for Aβ deposition and cytotoxicity during the progression of Alzheimer's disease (AD). Consequently, anti-Aβ monoclonal antibody drugs targeting Aβ oligomers and aggregation are considered potential therapeutic strategies for AD treatment. Similar to the working mechanisms of anti-Aβ monoclonal antibody drugs, our study identified osmundacetone (OAC), a small-molecule compound isolated from the traditional Chinese medicine Rhizoma Osmundae, as exerting anti-AD effects by targeting Aβ. PurposeThis study sought to determine whether OAC influences the Aβ burden in APP/PS1 mice and to identify potential regulatory mechanisms. MethodsFive-month-old APP/PS1 mice were injected intraperitoneally with OAC at a dose of 1 mg/kg for 12 weeks. The cognitive functions of the mice were assessed via the Morris water maze test and the open field test. Osmundacetone was analyzed via molecular docking, an isothermal dose‒response fingerprint-cellular context thermal shift assay, a thioflavine T fluorescence assay, and an atomic force microscopy assay to analyze the effects of OAC on Aβ fibrillation. Immunofluorescence, immunoblotting, and immunohistochemistry were used to assess Aβ clearance, AD pathology, oxidative stress, and inflammatory responses. ResultsThe innovative biochemical and physical data illustrated that the ability of OAC to inhibit Aβ fibrillation was accomplished by binding directly to Aβ, which differed from the majority of previously reported natural polyphenols that modulate the Aβ content and structure in an indirect manner. The inhibition of Aβ fibrosis by OAC subsequently promoted Aβ lysosomal degradation, resulting in a decreased Aβ burden in APP/PS1 mice. Furthermore, OAC treatment inhibited oxidative damage by upregulating glutathione peroxidase expression and attenuated the production of inflammatory factors by downregulating nuclear factor-kB phosphorylation in APP/PS1 mice. ConclusionThese findings demonstrate, for the first time, that OAC could reduce the brain Aβ burden in APP/PS1 mice by inhibiting Aβ fibrillation through direct binding to Aβ and improve cognitive dysfunction by attenuating oxidative damage and neuroinflammation. These findings indicate that OAC may be a promising candidate for the treatment of AD.

Improving the electromechanical deformability of MWCNT/silicone composites via encapsulating MWCNT with polyphenols and multilayered structure regulation

AbstractSilicone rubber (SR) is an ideal dielectric elastomer substrate due to its excellent flexibility and fast response speed. However, the innate low dielectric permittivity (ε) of SR generally requires a rather high driving voltage that restricts its widespread application. Typical attempts to increase ε of SR usually deteriorate either its flexibility or electrical stability. Herein, conductive multi‐walled carbon nanotube (MWCNT) were first surface modified with polyphenols (PNs) (MWCNT@PNs), aiming to facilitate its well dispersion within SR matrix, which may maintain the softness and electrical stability of SR via suppressing concentrated physical crosslinking and local leakage current flow. Then, five‐layered MWCNT@PNs/SR composites were prepared with the outer two insulating layers of SR while middle three dielectric layers of MWCNT@PNs filled SR. The multilayered structure further hindered the formation of conductive pathways through the composites, promising a high breakdown strength of the composites. Therefore, the multilayered MWCNT@PNs/SR composites exhibited increased ε, maintained low Young's modulus and electrical breakdown strength compared with pure SR of the same five‐layered structure. Among them, the composite with uniformly distributed MWCNT@PNs (m‐1: 1: 1) showed a highest actuation strain of 11.9% (at 19.6 kV mm−1), which was 4.1 times higher than that of SR (2.9% at 19.1 kV mm−1).

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles.

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-basedchemotherapy plus Gossypol with pro-apoptotic effects displays asynergisticeffect forkillingtumorcells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. Inthe patient-derived tumor xenograft (PDX)model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

Pterostilbene, a Dimethyl Derivative of Resveratrol, Exerts Cytotoxic Effects on Melanin-Producing Cells through Metabolic Activation by Tyrosinase.

Pterostilbene (PTS), which is abundant in blueberries, is a dimethyl derivative of the natural polyphenol resveratrol (RES). Several plant species, including peanuts and grapes, also produce PTS. Although RES has a wide range of health benefits, including anti-cancer properties, PTS has a robust pharmacological profile that includes a better intestinal absorption and an increased hepatic stability compared to RES. Indeed, PTS has a higher bioavailability and a lower toxicity compared to other stilbenes, making it an attractive drug candidate for the treatment of various diseases, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. We previously reported that RES serves as a substrate for tyrosinase, producing an o-quinone metabolite that is highly cytotoxic to melanocytes. The present study investigated whether PTS may also be metabolized by tyrosinase, similarly to RES. PTS was oxidized as a substrate by tyrosinase to form an o-quinone, which reacted with thiols, such as N-acetyl-L-cysteine, to form di- and tri-adducts. We also confirmed that PTS was taken up and metabolized by human tyrosinase-expressing 293T cells in amounts several times greater than RES. In addition, PTS showed a tyrosinase-dependent cytotoxicity against B16BL6 melanoma cells that was stronger than RES and also inhibited the formation of melanin in B16BL6 melanoma cells and in the culture medium. These results suggest that the two methyl groups of PTS, which are lipophilic, increase its membrane permeability, making it easier to bind to intracellular proteins, and may therefore be more cytotoxic to melanin-producing cells.

Targets and Mechanisms of Resveratrol against Endothelial-Mesenchymal Transition in Atherosclerosis: A Network Pharmacology Analysis Combined with In vivo Experiments

Background: Atherosclerosis (AS) is a chronic inflammatory disease characterized by plaque formation and endothelial dysfunction. Under pro-inflammatory conditions, the endothelial-mesenchymal transition (EndMT) plays an important role in the pathogenesis of AS. Resveratrol (RES) is a natural polyphenol in traditional Chinese medicines, which has been proven to possess anti-AS effects. However, the mechanism of RES treating AS through EndMT is not clear at present. Methods: RES targets were screened using databases such as SwissTargetPrediction and TargetNet, and AS and EndMT targets were searched using databases such as OMIM and DisGeNET. With the help of Venny 2.1, the key targets were selected by intersection. Next, the protein-protein interaction (PPI) network was constructed through the STRING 11.0 platform and Cytoscape software; gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations were performed using DAVID. Further, Cytoscape was used to construct a drug-component-gene target-pathway network diagram to identify the core components and genes. Subsequently, an AS rat model was established. The blood lipid level of rats was detected by an automatic biochemical analyzer, and the expression level of the target protein was measured by western blotting. Results: Through network pharmacology analysis, 37 potential targets for RES treating AS and EndMT were identified, and the core targets for RES treating AS consisted of AKT1, TNF, MIMP9, and PPARG. GO enrichment analysis indicated that the treatment of AS with RES mainly involved the migration and proliferation of epithelial and endothelial cells. The KEGG pathway enrichment analysis revealed that the enrichment of TNF and Rap1 signaling pathways was most significant. Besides, RES effectively reduced the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the serum of AS rats, increased the level of high-density lipoprotein cholesterol (HDL-C), and significantly cut down the atherosclerosis index (AI). Twist1, calponin, α-SMA and VE-cadherin were considered as EndMT indexes. The results of the western blot demonstrated that the protein levels of Twist1, calponin and α-SMA were significantly decreased, while the protein expression level of VE-cadherin was notably increased in rats treated with RES. Moreover, RES could also reduce the expression levels of Rap1 and Epac1 proteins. Conclusion: RES is an effective anti-AS drug. Briefly, RES can effectively improve the blood lipid level of AS patients, regulate the expression of EndMT-related proteins, and alleviate the dysfunction of endothelial cells. Notably, the functions of RES are closely associated with the EPAC1-Rap1 pathway.

Curcumin-Loaded Liposomes in Gel Protect the Skin of Mice against Oxidative Stress from Photodamage Induced by UV Irradiation.

Prolonged exposure to ultraviolet (UV) irradiation can cause oxidative stress in the skin, accompanied by rapid immunosuppressive effects, resulting in a peroxidation reaction throughout the body. Curcumin (Cur), as the bioactive compound of turmeric, is a natural polyphenol with potent antioxidant properties but is often overlooked due to its poor solubility and low bioavailability. In this study, curcumin-loaded liposomes in a sodium alginate gel complex preparation were designed to improve the bioavailability of curcumin and to study its preventive effect on photodamage. Cur-loaded liposomes (Cur-L), Cur-loaded gel (Cur-G) based on an alginate matrix, and curcumin-loaded liposomes in gel (Cur-LG) were prepared, and their antioxidant effects and drug diffusion abilities were evaluated. The antioxidant capacity of Cur, Cur-L, Cur-G, and Cur-LG was also studied in a mouse model of photodamage. Cur had the highest antioxidant activity at about 4 mg/mL. Cur-LG at this concentration showed antioxidant effects during 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and H2O2 experiments. During the UV light damage test, Cur-LG demonstrated the ability to effectively neutralize free radicals generated as a result of lipid peroxidation in the skin, serum, and liver, thereby enhancing the overall activity of superoxide dismutase (SOD). In conclusion, using Cur-LG may protect against epidermal and cellular abnormalities induced by UV irradiation.

Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts.

Pancreatic cancer, a formidable gastrointestinal neoplasm, is characterized by its insidious onset, rapid progression, and resistance to treatment, which often lead to a grim prognosis. While the complex pathogenesis of pancreatic cancer is well recognized, recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts. However, their precise role in pancreatic cancer remains unknown. Resveratrol is a natural polyphenol known for its multifaceted biological actions, including antioxidative and neuroprotective properties, as well as its potential to inhibit tumor proliferation and migration. Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis. To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts. Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression of α-SMA and p16. HP-1 expression was determined using immunohistochemistry. Cells were treated with the senescence-inducing factors known as 3CKs. Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate. Western blotting was conducted to assess the expression levels of p16 and p21. Immunofluorescence was performed to assess LaminB1 expression. Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors, including IL-4, IL-6, IL-8, IL-13, MMP-2, MMP-9, CXCL1, and CXCL12. A scratch assay was used to assess the migratory capacity of the cells, whereas Transwell assays were used to evaluate their invasive potential. Specifically, we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues, linking their abundance to cancer progression. Intriguingly, Resveratrol effectively eradicated these fibroblasts and hindered their senescence, which consequently impeded pancreatic cancer progression. This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.

Chlorogenic Acid Enhances the Intestinal Health of Weaned Piglets by Inhibiting the TLR4/NF-κB Pathway and Activating the Nrf2 Pathway.

Chlorogenic acid (CGA) is a natural polyphenol with potent antioxidant and anti-inflammatory activities. However, the exact role of it in regulating intestinal health under oxidative stress is not fully understood. This study aims to investigate the effects of dietary CGA supplementation on the intestinal health of weaned piglets under oxidative stress, and to explore its regulatory mechanism. Twenty-four piglets were randomly divided into two groups and fed either a basal diet (CON) or a basal diet supplemented with 200 mg/kg CGA (CGA). CGA reduced the diarrhea rate, increased the villus height in the jejunum, and decreased the crypt depth in the duodenum, jejunum, and ileum of the weaned piglets (p < 0.05). Moreover, CGA increased the protein abundance of Claudin-1, Occludin, and zonula occludens (ZO)-1 in the jejunum and ileum (p < 0.05). In addition, CGA increased the mRNA expression of pBD2 in the jejunum, and pBD1 and pBD2 in the ileum (p < 0.05). The results of 16S rRNA sequencing showed that CGA altered the ileal microbiota composition and increased the relative abundance of Lactobacillus reuteri and Lactobacillus pontis (p < 0.05). Consistently, the findings suggested that the enhancement of the intestinal barrier in piglets was associated with increased concentrations of T-AOC, IL-22, and sIgA in the serum and T-AOC, T-SOD, and sIgA in the jejunum, as well as T-AOC and CAT in the ileum caused by CGA (p < 0.05). Meanwhile, CGA decreased the concentrations of MDA, IL-1β, IL-6, and TNF-α in the serum and jejunum and IL-1β and IL-6 in the ileum (p < 0.05). Importantly, this study found that CGA alleviated intestinal inflammation and oxidative stress in the piglets by inhibiting the TLR4/NF-κB signaling pathway and activating the Nrf2 signaling pathway. These findings showed that CGA enhances the intestinal health of weaned piglets by inhibiting the TLR4/NF-κB pathway and activating the Nrf2 pathway.

Mini Review: Antimicrobial Agents Based on Natural Compounds: The Key to Solving the Current Crisis

Context: The rapid development of resistance mechanisms by bacteria has led to the loss of effectiveness of many commonly used antibiotics, posing a serious threat to global public health. Therefore, the objective of this study is to provide further insights into combating antibiotic resistance and addressing the urgent need for additional effective antimicrobial treatments as alternatives. Methods: In this narrative review, natural compounds derived from plants, fungi, and other sources were evaluated for their antimicrobial properties based on clinical trials and in vitro studies. These compounds have gained attention due to their potential to serve as alternative or adjunctive therapies. Results: We briefly reviewed and introduced antibacterial agents derived from natural substances and extracts as an alternative solution to the current crisis. Many natural sources, such as antimicrobial peptides (AMPs), nanoparticles, enzyme disruption of acylhomoserine lactones (AHLs), Mur enzymes, lysocine E, plant-derived natural products, polyphenols, nanozymes, antimicrobial peptidomimetics, and antimicrobials of fungal origin (such as penicillin, griseofulvin, amphotericin B, echinocandins, and statins), produce a wide range of secondary metabolites with the potential to exhibit antibacterial activity. Moreover, natural products often possess complex chemical structures, which can target multiple bacterial pathways, enhancing their ability to inhibit or kill bacteria. Conclusions: This study contributes new knowledge and perspectives on combating antibiotic resistance by exploring alternative treatments and natural products, which represent an important area of research. It may offer new solutions to address the urgent need for effective antimicrobial treatments. Further research is necessary to isolate, identify, and characterize the active compounds, study their mechanisms of action, optimize their efficacy and safety, and evaluate their potential for clinical use.