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The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of Arctium lappa, with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.

[Display omitted] Although photothermal therapy (PTT) is effective at killing tumor cells, it can inadvertently damage healthy tissues surrounding the tumor. Nevertheless, lowering the treatment temperature will reduce the therapeutic effectiveness. In this study, we employed 2,2′-((2Z,2′Z)-((4,4,9,9-Tetrahexyl-4,9-dihydro-s-indaceno[1,2- b :5,6- b ']dithiophene-2,7-diyl)bis(methanylylidene))bis(3-oxo-2,3-dihydro-1H-indene-2,1-diylidene)) dimalononitrile (IDIC), a molecule possessing a conventional acceptor–donor-acceptor (A-D-A) structure, as a photothermal agent (PTA) to facilitate effective mild photothermal therapy (mPTT). IDIC promotes intramolecular charge transfer under laser irradiation, making it a promising candidate for mPTT. To enhance the therapeutic potential of IDIC, we incorporated quercetin (Qu) into IDIC to form IDIC-Qu nanoparticles (NPs), which can inhibit heat shock protein (HSP) activity during the process of mPTT. Moreover, IDIC-Qu NPs exhibited exceptional water dispersibility and passive targeting abilities towards tumor tissues, attributed to its enhanced permeation and retention (EPR) effect. These advantageous properties position IDIC-Qu NPs as a promising candidate for targeted tumor treatment. Importantly, the IDIC-Qu NPs demonstrated controllable photothermal effects, leading to outstanding in vitro cytotoxicity against cancer cells and effective in vivo tumor ablation through mPTT. IDIC-Qu NPs nano-system enriches the family of organic PTAs and holds significant promise for future clinical applications of mPTT. [ABSTRACT FROM AUTHOR]

A wide range of active agents, synthetic and natural agents such as essential oils, chitosan and polyphneols consisting of curcumin, gallic acid, anthocyanins, and catechins have been used in order to develop antimicrobial packaging systems, and among them, natural polyphenolic compounds, specially curcumin (Cur) has great potential due to effective biological activities in developing food packaging material. Quercetin (Quer) is also the mostly studied flavonol as a color‐changing indicator in the food industry and has been already developed as a realistic alternative for smart and active food packaging. The reason for choosing these two polyphenolic compounds is that they simultaneously possess many beneficial properties such as antioxidant, antibacterial, antiviral, antitumoral, and anti‐inflammatory effects. Additionally, the main objective of the study is to combine polypropylene (PP), which is the most preferred and cost‐effective polymer in the packaging industry, with these active ingredients, rather than using more expensive polymer types. In this context, PP‐Quer or PP‐Cur membranes, which are new experiences based on these literatures were chemically characterized by Fourier transform infrared spectroscopy, and the surface morphology of these composite membranes was characterized by scanning electron microscopy. The antibacterial response against gram‐positive (Staphylococcus aureus) and gram‐negative (Escherichia coli) bacteria species was investigated. Furthermore, the reactive oxygen species generation and anticancer activity of these composite membranes using human colorectal adenocarcinoma (HT‐29) were observed. We proposed that PP‐Quer or PP‐Cur composite membranes can be a potential candidate as active packaging material in the food industry. [ABSTRACT FROM AUTHOR]

Chemotherapy-associated side effects significantly contribute to the challenges of cancer treatment, impacting the well-being of patients and complicating existing conditions. Chemotherapy-induced oedema, characterized by abnormal fluid accumulation and swelling, worsens cancer-related issues, such as impaired wound healing. This oedema may result from drug-induced vascular changes and electrolyte imbalances. Addressing such side effects is crucial for improving prognostic outcomes of cancer patients. The rat paw oedema model is a valuable tool for studying inflammatory oedema, testing novel therapies, and understanding their mechanisms. Conventional treatments for cancer chemotherapy-induced oedema have limitations, highlighting the need for alternative or complementary approaches, such as exploring natural products like Syzygium aromaticum (clove), known for its anti-inflammatory properties and potential to alleviate edema. This study examined the effects of Syzygium aromaticum ethanol extract on inflammatory oedema in rats, identified the responsible active compound (s), and explored the possible mechanism involved through computational modeling. Ethanol extract of Syzygium aromaticum (SAEE) was prepared. In vivo anti-inflammatory activities of the extract were evaluated at a specific controlled timeframe in formalin-induced paw oedema in Wistar rats. The binding affinities and interactions of the initially identified chemical constituents of the extract were modeled, through Glide standard precision and quantum polarized ligand docking, against cyclooxygenase-2 for their potential for their possible inhibitory mechanism. SAEE displayed significant time- and dose-dependent amelioration of inflammatory oedema and dose-dependent inhibition of key proinflammatory cytokines in the rat models. In silico modeling of identified SAEE compounds revealed delphinidin, rhamnetin, and quercetin as responsible for the observed in vivo protective effects of SAEE in rat paw oedema models. This study found that Syzygium aromaticum ethanol extract effectively reduced inflammation-induced paw swelling and modulated key inflammatory markers in the rats, with the inhibitory activities of constituting delphinidin, quercetin, and rhamnetin against cyclooxygenase 2 being possibly responsible for the observed in vivo effects. Further experimental validation and dynamic simulations are needed to confirm their potential potency in more advanced preclinical and clinical models, as well as explore the mechanistic pathways involved. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective(s): Liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), pose significant global public health challenges. This study investigates the therapeutic effects of quercetin (QC), Capparis spinosa (CS), a QC and CS combination, and Saroglitazar (SARO) on NASH in a Wistar rat model. Materials and Methods: NASH was induced by a 42-day high-fat diet regimen in male Wistar rats. Post-induction, rats were divided into five groups receiving SARO, QC, CS, and CS+QC combination. We monitored changes in liver and body weights and evaluated the expression of genes associated with fatty acid biosynthesis (e.g., ACC and FAS), β-oxidation (e.g., CPT1, PPAR α), inflammation (e.g., TNF-α and IL-6), and fibrosis (e.g., TGF-β and COL1A), as well as protein expression levels of p-Smad2/3 and p-Smad3. Results: Treatment with QC+CS significantly decreased liver weight, body mass gain, and liver triglyceride (TG) compared to other treatments. The QC and CS combined therapy also resulted in a greater normalization of hepatic enzymatic activities, including decreases in ALT and AST levels, coupled with improvements in lipid profile indicated by decreased LDL-C and increased HDL-C concentrations, as compared to SARO and QC alone. Furthermore, this combined treatment significantly down-regulated the expression of TGF-β, TNF-α, IL-6 genes, and Smad2/3 and Smad3 protein levels. Conclusion: Our study demonstrates that an interactive effect between QC and CS can effectively reduce liver fibrosis and steatosis by inhibiting the TGF-β/Smad3 signaling pathway in a diet-induced model of nonalcoholic steatohepatitis and fibrosis in rats. [ABSTRACT FROM AUTHOR]

This investigation aims at providing a novel approach to producing high-performance antioxidant material. Indeed, quercetin molecules incorporated into collagen/chitosan/SiO2 composite through direct interactions have been reported for the first time. Such internal linking has been found as the primary reason for improving the stability of the entire system and enhancing the permanent existence of strongly active biomaterials. Consequently, in vitro antioxidant tests revealed that the obtained materials (denoted as CS/Col/SiO2/Q) provide outstanding antioxidant activity. Thus the CS/Col/SiO2/Q sample exhibits cytotoxicity to HepG2, MKN7, and MCF-7 cancer cells. These results demonstrate that the obtained composite turns out to be very promising as a bioactive material for biomedical applications. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction was a common symptom of major depressive disorder (MDD). In previous studies, psychological stress leads to activation and proliferation of microglial cells in different brain regions. Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. To demonstrate the role of quercetin in the hippocampal inflammatory response in depress mice. The chronic unpredictable stress (CUS) depressive mice model built is used to explore the protective effects of quercetin on depression. Neurobehavioral test, protein expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and heat shock protein 90 (HSP90), and cytokines (IL-6, IL-1β, MCP-1, and TNF-α) were assessed. Quercetin ameliorated depressive-like behavior and cognitive impairment, and quercetin attenuates neuroinflammation and by targeting HSP90 to inhibit NLRP3 inflammasome activation. Quercetin inhibited the increase of HSP90 levels in the hippocampus and reverses inflammation-induced cognitive impairment. Besides, quercetin inhibited the increased level of cytokines (IL-6, IL-1β, MCP-1, and TNF-α) in the hippocampus of the depressive model mouse and the increased level of cytokines (IL-6, IL-1β, and MCP-1) in microglia. The current study indicated that quercetin mitigated depressive-like behavior and by targeting HSP90 to inhibit NLRP3 inflammasome activation in microglia and depressive mice model, meanwhile ameliorated cognitive impairment in depression. Quercetin has huge potential for the novel pharmacological efficacy of antidepressant therapy. [ABSTRACT FROM AUTHOR]

Critical‐sized bone defects pose a significant challenge in advanced healthcare due to limited bone tissue regenerative capacity. The complex interplay of numerous overlapping variables hinders the development of multifunctional biocomposites. Phytochemicals show promise in promoting bone growth, but their dose‐dependent nature and physicochemical properties halt clinical use. To develop a comprehensive solution, a 3D‐printed (3DP) extrusion‐based tricalcium phosphate‐polycaprolactone (TCP‐PCL) scaffold is augmented with quercetin and potassium chloride (KCl). This composite material demonstrates a compressive strength of 30 MPa showing promising stability for low load‐bearing applications. Quercetin release from the scaffold follows a biphasic pattern that persists for up to 28 days, driven via diffusion‐mediated kinetics. The incorporation of KCl allows for tunable degradation rates of scaffolds and prevents the initial rapid release. Functionalization of scaffolds facilitates the attachment and proliferation of human fetal osteoblasts (hfOB), resulting in a 2.1‐fold increase in cell viability. Treated scaffolds exhibit a 3‐fold reduction in osteosarcoma (MG‐63) cell viability as compared to untreated substrates. Ruptured cell morphology and decreased mitochondrial membrane potential indicate the antitumorigenic potential. Scaffolds loaded with quercetin and quercetin‐KCl (Q‐KCl) demonstrate 76% and 89% reduction in bacterial colonies of Staphylococcus aureus, respectively. This study provides valuable insights as a promising strategy for bone tissue engineering (BTE) in orthopedic repair. [ABSTRACT FROM AUTHOR]

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Radioresistance poses a significant obstacle in cancer treatment. Lotus seedpod extract (LSE) has demonstrated anticancer effects in various cancer cells. However, its potential against radioresistant tumors remains unclear. In this study, we aimed to investigate the effect of LSE on radioresistant breast cancer cells, explore the underlying mechanism, and identify the major constituents responsible for its cytotoxic effect. LSE, extracted using 70% ethanol, exhibited selective cytotoxic effects against radioresistant breast cancer cells compared with their parental cells. Chemical analysis identified quercetin and its derivatives, hyperoside and miquelianin, as the major constituents responsible for these selective effects. Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor‐bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. This study provides compelling evidence to support the use of LSE as a medicinal source for the future adjunctive therapy to combat radioresistance in breast cancers. [ABSTRACT FROM AUTHOR]

A photoelectrochemical (PEC) biosensor with a wide linear detection range was developed for the sensitive detection of neuron-specific enolase (NSE), which was achieved by applying a photocurrent polarity transition strategy mediated by quercetin. The coupling reaction between Cr(VI) and quercetin drives the signal polarity from anodic to cathodic. When only quercetin is present in the test solution, photogenerated electrons are transferred to the electrode to generate anodic photocurrent. However, in the presence of the target, the signal probe released Cr(VI), which interacted with quercetin, and the electron transfer direction was changed to achieve signal polarity conversion. Meanwhile, protoporphyrin-sensitized Bi:SrTiO3 nanocubes were used as matrix photoactive materials to provide basic photocurrent. The doping of Bi element would adjust the bandgap of SrTiO3, and the organic–inorganic composite material exhibits good photostability and chemical stability that can maintain stable photoelectric properties over a long period of time. Such a novel signal polarity transition strategy greatly broadened the sensor detection to the range of 0.00007–170 ng mL−1 and obtained a relatively low detection limit (25 fg mL−1), which greatly improved the detection sensitivity and accuracy of the biosensor. [ABSTRACT FROM AUTHOR]

Although phytochemicals are plant-derived toxins that are primarily produced as a form of defense against insects or microbes, several lines of study have demonstrated that the phytochemical, quercetin, has several beneficial biological actions for human health, including antioxidant and inflammatory effects without side effects. Quercetin is a flavonoid that is widely found in fruits and vegetables. Since recent studies have demonstrated that quercetin can modulate neuronal excitability in the nervous system, including nociceptive sensory transmission via mechanoreceptors and voltage-gated ion channels, and inhibit the cyclooxygenase-2-cascade, it is possible that quercetin could be a complementary alternative medicine candidate; specifically, a therapeutic agent against nociceptive and pathological pain. The focus of this review is to elucidate the neurophysiological mechanisms underlying the modulatory effects of quercetin on nociceptive neuronal activity under nociceptive and pathological conditions, without inducing side effects. Based on the results of our previous research on trigeminal pain, we have confirmed in vivo that the phytochemical, quercetin, demonstrates (i) a local anesthetic effect on nociceptive pain, (ii) a local anesthetic effect on pain related to acute inflammation, and (iii) an anti-inflammatory effect on chronic pain. In addition, we discuss the contribution of quercetin to the relief of nociceptive and inflammatory pain and its potential clinical application. [ABSTRACT FROM AUTHOR]

Simple Summary: The protein oxidation of soybean meal, resulting from storage, can detrimentally impact the intestinal digestive and absorptive functions in animals. Meanwhile, quercetin can regulate protein and lipid metabolism, intestinal transporter numbers, and gut microbiota in animals. The aim of this study was to investigate the effect of quercetin supplementation on the intestinal digestive and absorptive functions and microbiota in rats fed protein-oxidized soybean meal. The results of this study indicated that the protein-oxidized soybean meal decreased the relative weights of the digestive organs and the duodenal villus height, thereby reducing the apparent ileal digestibility of amino acids in the rats. Transcriptomics and microbiomics revealed that quercetin supplementation alleviated these adverse effects primarily by upregulating the pathway of intestinal amino acid transmembrane transporter activity and improving the cecal microbial composition. To clarify the nutritional mechanisms of quercetin mitigation in the digestive and absorptive functions in rats fed protein-oxidized soybean meal, 48 three-week-old male SD rats were randomly allocated into a 2 × 2 factorial design with two soybean meal types (fresh soybean meal or protein-oxidized soybean meal) and two quercetin levels (0 or 400 mg/kg) for a 28-day feeding trial. The protein-oxidized soybean meal treatment decreased (p < 0.05) the relative weights of the pancreas, stomach, and cecum, duodenal villus height, pancreatic and jejunal lipase activities, apparent ileal digestibility of amino acids, and apparent total tract digestibility of dry matter, crude protein, and ether extract. The supplementation of quercetin in the protein-oxidized soybean meal diet reversed (p < 0.05) the decreases in the duodenal length, ileal villus height, lipase activity, apparent ileal digestibility of amino acids, and apparent total tract digestibility of dry matter, crude protein, and ether extract. Transcriptomics revealed that the "alanine transport" and "lipid digestion and absorption" pathways were downregulated by the protein-oxidized soybean meal compared with fresh soybean meal, while the "basic amino acid transmembrane transporter activity" and "lipid digestion and absorption" pathways were upregulated by the quercetin supplementation. Microbiomics revealed that the protein-oxidized soybean meal increased the protein-degrading and inflammation-triggering bacteria in the cecum, while the relative abundances of beneficial bacteria were elevated by the quercetin supplementation. [ABSTRACT FROM AUTHOR]

It is still unclear whether or how quercetin influences the toxic events induced by acetaldehyde in hepatocytes, though quercetin has been reported to mitigate alcohol-induced mouse liver injury. In this study, we evaluated the modulating effect of quercetin on the cytotoxicity induced by acetaldehyde in mouse hepatoma Hepa1c1c7 cells, the frequently used cellular hepatocyte model. The pretreatment with quercetin significantly inhibited the cytotoxicity induced by acetaldehyde. The treatment with quercetin itself had an ability to enhance the total ALDH activity, as well as the ALDH1A1 and ALDH3A1 gene expressions. The acetaldehyde treatment significantly enhanced the intracellular reactive oxygen species (ROS) level, whereas the quercetin pretreatment dose-dependently inhibited it. Accordingly, the treatment with quercetin itself significantly up-regulated the representative intracellular antioxidant-related gene expressions, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase, catalytic subunit (GCLC), and cystine/glutamate exchanger (xCT), that coincided with the enhancement of the total intracellular glutathione (GSH) level. Tin protoporphyrin IX (SNPP), a typical HO-1 inhibitor, restored the quercetin-induced reduction in the intracellular ROS level, whereas buthionine sulphoximine, a representative GSH biosynthesis inhibitor, did not. SNPP also cancelled the quercetin-induced cytoprotection against acetaldehyde. These results suggest that the low-molecular-weight antioxidants produced by the HO-1 enzymatic reaction are mainly attributable to quercetin-induced cytoprotection. [ABSTRACT FROM AUTHOR]

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 μM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin. [ABSTRACT FROM AUTHOR]

Nanotechnology has significantly impacted human life, particularly in overcoming the limitations associated with neurodegenerative diseases (NDs). Various nanostructures and vehicle systems, such as polymer nanoparticles, carbon nanotubes (CNTs), nanoliposomes, nano-micelles, lipid nanoparticles, lactoferrin, polybutylcyanoacrylate, and poly lactic-co-glycolic acid, have been shown to enhance drug efficacy, reduce side effects, and improve pharmacokinetics. NDs affect millions worldwide and are challenging to treat due to the blood-brain barrier (BBB), which hinders drug delivery to the central nervous system (CNS). Research suggests that natural ingredients can be formulated into nanoparticles, offering a promising approach for ND treatment. This review examines the advantages and disadvantages of herbal-based nanoformulations, highlighting their potential effectiveness when used alone or in combination with other medications. Herbal nanoparticles provide benefits over synthetic ones due to their biocompatibility, reduced toxicity, and potential for synergistic effects. The study's findings can be applied to develop more efficient drug delivery systems, improving the treatment of NDs by enhancing drug penetration across the BBB and targeting affected CNS areas more precisely. [ABSTRACT FROM AUTHOR]

To obtain oil from bee brood, which was dried using a tray drying method, this study used the supercritical CO2 extraction method. Extraction occurred at temperatures between 40–60 °C and low pressures of 180–220 bar for 1.5 h, with a high pressure of 600 bar for 1 h. The study investigated both the yield and chemical properties of the extracted bee brood oils. Supercritical CO2 extraction of tray-dried bee brood at 600 bar pressure demonstrated higher oil extraction efficiency compared to lower pressures (180–220 bar). At temperatures of 40–60 °C, total phenolic compounds increased while total flavonoids decreased. The extracted oil exhibited antioxidant activity, primarily due to quercetin. Despite decreased acid, iodine, and saponification values, peroxide value slightly increased but remained below 12 meqO2/kg of oil. The make-up of the fatty acids changed. At 600 bar, palmitic and oleic acids were the most common, while myristic, linoleic, and docosadienoic acids decreased. At 600 bar, eicosadienoic acid was absent. The defatted bee brood retained significant essential and non-essential amino acids, indicating its potential for further development as a protein source. [ABSTRACT FROM AUTHOR]

Background: Patients with endometriosis suffer with chronic pelvic pain and infertility, and from the lack of pharmacologic therapies that consistently halt disease progression. Differences in the endometrium of patients with endometriosis vs. unaffected controls are well-documented. Specifically, shed endometrial tissues (delivered to the pelvic cavity via retrograde menstruation) reveal that a subset of stromal cells exhibiting pro-inflammatory, pro-fibrotic, and pro-senescence-like phenotypes is enhanced in endometriosis patients compared to controls. Additionally, cultured biopsy-derived endometrial stromal cells from endometriosis patients exhibit impaired decidualization, a defined differentiation process required for human embryo implantation and pregnancy. Quercetin, a senolytic agent, shows therapeutic potential for pulmonary fibrosis, a disorder attributed to senescent pulmonary fibroblasts. In rodent models of endometriosis, quercetin shows promise, and quercetin improves decidualization in vitro. However, the exact mechanisms are not completely understood. Therefore, we investigated the effects of quercetin on menstrual effluent-derived endometrial stromal cells from endometriosis patients and unaffected controls to define the signaling pathways underlying quercetin's effects on endometrial stromal cells. Methods: Menstrual effluent-derived endometrial stromal cells were collected and cultured from unaffected controls and endometriosis patients and then, low passage cells were treated with quercetin (25 µM) under basal or standard decidualization conditions. Decidualization responses were analyzed by measuring the production of IGFBP1 and PRL. Also, the effects of quercetin on intracellular cAMP levels and cellular oxidative stress responses were measured. Phosphokinase arrays, western blotting, and flow cytometry methods were performed to define the effects of quercetin on various signaling pathways and the potential mechanistic roles of quercetin. Results: Quercetin significantly promotes decidualization of control- and endometriosis-endometrial stromal cells. Quercetin substantially reduces the phosphorylation of multiple signaling molecules in the AKT and ERK1/2 pathways, while enhancing the phosphorylation of p53 and total p53 levels. Furthermore, p53 inhibition blocks decidualization while p53 activation promotes decidualization. Finally, we provide evidence that quercetin increases apoptosis of endometrial stromal cells with a senescent-like phenotype. Conclusions: These data provide insight into the mechanisms of action of quercetin on endometrial stromal cells and warrant future clinical trials to test quercetin and other senolytics for treating endometriosis. [ABSTRACT FROM AUTHOR]

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug‐controlled delivery system is constructed as a bone‐enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug‐carrying system made up of nanoscale bioglass microspheres and a light‐cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1‐dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy. [ABSTRACT FROM AUTHOR]

Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging. [ABSTRACT FROM AUTHOR]

sEVs-Que promoted the recovery of motor function in rats with spinal cord injury. [Display omitted] • sEVs reduce the degradation of Que and accumulate at the SCI site. • sEVs-Que reduce inflammation via the TLR4/NF-κB pathway. • sEVs-Que reduce the astrocyte scar through the JAK2/STAT3 pathway. • sEVs-Que promote the recovery of motor function in rats with SCI. Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood–brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury. [ABSTRACT FROM AUTHOR]

Natural compounds have been used since the earliest civilizations and remain, to this day, a safer alternative for treating various dental problems. These present antimicrobial, anti-inflammatory, antioxidant, analgesic, and antimutagenic effects, making them useful in the prophylactic and curative treatment of various oral diseases such as infections, gingivitis, periodontitis, and even cancer. Due to the high incidence of unpleasant adverse reactions to synthetic compounds, natural products tend to gradually replace conventional treatment, as they can be just as potent and cause fewer, milder adverse effects. Researchers use several methods to measure the effectiveness and safety profile of these compounds, and employing standard techniques also contributes to progress across all medical disciplines. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus biofilm formation is a pivotal mechanism in the development of drug resistance, conferring resilience against conventional antibiotics. This study investigates the inhibitory effects of Actinostemma lobatum (A. lobatum) Maxim extracts on S. aureus biofilm formation and their antihemolytic activities, with a particular focus on identifying the active antibiofilm and antihemolysis compound, quercetin. Seven solvent extracts and twelve sub-fractions were evaluated against four S. aureus strains. The ethyl acetate fraction (10 to 100 μg/mL) significantly hindered biofilm formation by both methicillin-sensitive and -resistant strains. Bioassay-guided isolation of the ethyl acetate extract identified quercetin as the major antibiofilm compound. The ethyl acetate extract was found to contain 391 μg/mg of quercetin and 30 μg/mg of kaempferol. Additionally, the A. lobatum extract exhibited antihemolytic activity attributable to the presence of quercetin. The findings suggest that quercetin-rich extracts from A. lobatum and other quercetin-rich foods and plants hold promise for inhibiting resilient S. aureus biofilm formation and attenuating its virulence. [ABSTRACT FROM AUTHOR]

Introduction: Traditional Chinese medicinal plant, safflower, shows effective for treating pulmonary arterial hypertension (PAH), yet the underlying mechanisms remain largely unexplored. This study is aimed at exploring the potential molecular mechanisms of safflower in the treatment of PAH. Methods: Network pharmacology approach and molecular docking were applied to identify the core active compounds, therapeutic targets, and potential signaling pathways of safflower against PAH. Meanwhile, high‐performance liquid chromatography (HPLC) assay was performed to determine the core compounds from safflower. Further, the mechanism of action of safflower on PAH was verified by in vivo and in vitro experiments. Results: A total of 15 active compounds and 177 targets were screened from safflower against PAH. Enrichment analysis indicated that these therapeutic targets were mainly involved in multiple key pathways, such as TNF signaling pathway and Th17 cell differentiation. Notably, molecular docking revealed that quercetin (core compound in safflower) displayed highest binding capacity with NLRP3. In vivo, safflower exerted therapeutic effects on PAH by inhibiting right ventricular hypertrophy, inflammatory factor release, and pulmonary vascular remodeling. Mechanistically, it significantly reduced the expression of proangiogenesis‐related factors (MMP‐2, MMP‐9, Collagen 1, and Collagen 3) and NLRP3 inflammasome components (NLRP3, ASC, and Caspase‐1) in PAH model. Similarly, these results were observed in vitro. Besides, we further confirmed that NLRP3 inhibitor had the same therapeutic effect as safflower in vitro. Conclusion: Our findings suggest that safflower mitigates PAH primarily by inhibiting NLRP3 inflammasome activation. This provides novel insights into the potential use of safflower as an alternative therapeutic approach for PAH. [ABSTRACT FROM AUTHOR]

Transmembrane protease/serine (TMPRSS2), a type II transmembrane serine protease, plays a crucial role in different stages of cancer. Recent studies have reported that the triggering epidermal growth factor receptor (EGFR) activation through protease action promotes metastasis. However, there are no reports on the interaction of TMPRSS2 with EGFR, especially in triple‐negative triple negative (TNBC). The current study investigates the unexplored interaction between TMPRSS2 and EGFR, which are key partners mediating metastasis. This interaction is explored for potential targeting using quercetin (QUE) and taxifolin (TAX). TMPRSS2 expression patterns in breast cancer (BC) tissues and subtypes have been predicted, with the prognostic significance assessed using the GENT2.0 database. Validation of TMPRSS2 expression was performed in normal and TNBC tissues, including drug‐resistant cell lines, utilizing GEO datasets. TMPRSS2 was further validated as a predictive biomarker for FDA‐approved chemotherapeutics through transcriptomic data from BC patients. The study demonstrated the association of TMPRSS2 with EGFR through in silico analysis and validates the findings in TNBC cohorts using the TIMER2.0 web server and the TCGA dataset through C‐Bioportal. Molecular docking and molecular dynamic simulation studies identified QUE and TAX as best leads targeting TMPRSS2. They inhibited cell‐free TMPRSS2 activity like clinical inhibitor of TMPRSS2, Camostat mesylate. In cell‐based assays focused on paclitaxel‐resistant TNBC (TNBC/PR), QUE and TAX demonstrated potent inhibitory activity against extracellular and membrane‐bound TMPRSS2, with low IC50 values. Furthermore, ELISA and cell‐based AlphaLISA assays demonstrated that QUE and TAX inhibit the interaction of TMPRSS2 with EGFR. Additionally, QUE and TAX exhibited significant inhibition of proliferation and cell cycle accompanied by notable alterations in the morphology of TNBC/PR cells. This study provides valuable insights into potential of QUE and TAX targeting TMPRSS2 overexpressing TNBC. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive experiment within the interdisciplinary field of chemical biology, closely aligned with the cutting-edge of the discipline, deeply integrating science and education. Utilizing both chemical and biological methods within an in vitro biochemical reaction system, this study investigates effects of the natural antioxidant quercetin on the redox cycle of myeloperoxidase (MPO) within biological organisms. The mechanism of quercetin affecting the chlorination activity of MPO is clarified through molecular docking techiniques and a series of UV-Vis absorption spectroscopy. The implementation of this experiment aids in broadening students’ perspectives, igniting their interest in scientific research, and enhancing their comprehensive experimental abilities. It offers valuable insights and examples for the development of multidisciplinary innovative talents in chemistry-related majors. [ABSTRACT FROM AUTHOR]

Electrochemical alkalization of (Cu–S)n metal–organic framework (MOF) and graphene oxide ((Cu–S)n MOF/GO) composite yields a new CuO/(Cu–S)n MOF/RGO (reduced GO) composite with porous morphology on screen printed carbon electrode (SPCE) which facilitated the electron transfer properties in electrochemical quercetin (QUE) detection. A selective QUE detection ability has been demonstrated by the constructed electrochemical sensor (CuO/(Cu–S)n MOF/RGO/SPCE), which also has a broad dynamic range of 0.5 to 115 µM in pH 3 by differential pulse voltammetry. The detection limit is 0.083 µM (S/N = 3). In this study, it was observed that the real samples contained 0.34 mg mL−1 and 27.7 µg g−1 QUE in wine and onion, respectively. [ABSTRACT FROM AUTHOR]

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2–24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 μM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy. [ABSTRACT FROM AUTHOR]

Chemical signals are crucial in mediating ecological and evolutionary adaptation of plants to their environments. Indeed, invasive plants may produce greater amounts of chemical metabolites in their new ranges. Some of these chemicals can enhance their mutualistic interactions and improve invasive plant performance, but genetic mechanisms of such adaptations are unexplored.We used Triadica sebifera plants as a model to investigate evolutionary changes in chemical signals that enhance arbuscular mycorrhizal (AM) fungal associations. Previous studies found that T. sebifera plants from invasive populations had higher root exudate concentrations of the flavonoid quercetin and elevated AM fungal colonization compared with those from native populations. Here, we explored genetic variation in strigolactone concentrations in root exudates and their contribution to AM fungal colonization with strigolactone analogue GR24 additions. In addition, we studied how gene expression patterns related to flavonoid and strigolactone biosynthesis varied among invasive and native populations using comparative genomics, transcriptomics and fluorescent real‐time quantitative PCR.We found that plants from invasive populations had higher concentrations of the strigolactone 5‐deoxystrigol in root exudates that were correlated with higher AM fungal colonization rates, relative to those from native populations. Exogenous applications of GR24, a synthetic analogue of 5‐deoxystrigol, increased AM fungal colonization. We found higher expression of a single gene in flavonoid (FLS) and strigolactone (DAD1) biosynthesis pathways increased levels of quercetin and 5‐deoxystrigol in plants from invasive populations, respectively.Synthesis. Understanding the role of genetic evolution in enhancing mutualisms of invasive plants provides new insights into the underlying mechanisms of plant invasion. This study suggests that an invasive plant enhanced its mutualisms by upregulating the expression of key genes related to secondary metabolites in root exudates which stimulate symbiotic relationships with AM fungi. Thus, these findings provide insights into genetic mechanisms that underlie higher AM fungal colonization and enhanced invasive plant performance. [ABSTRACT FROM AUTHOR]

Inflammatory responses play a crucial role in the pathophysiology of spinal cord injury (SCI) and developing new approaches to establish an anti-inflammatory environment for the promotion of neuroregeneration holds promise as a potential approach. In this study, our aim was to investigate the potential of combining an acellular spinal cord scaffold (ASCS) with quercetin-loaded bovine serum albumin (Qu/BSA) nanoparticles (NPs) for the treatment of SCI. The ASCS was prepared using physical and chemical methods, while the Qu/BSA NPs were prepared through a desolvation technique. The NPs exhibited favorable characteristics, including a mean size of 203 nm, a zeta potential of –38, and an encapsulation efficiency of 96%. Microscopic evaluation confirmed the successful distribution of NPs on the walls of ASCS. Animal studies revealed that Qu/BSA NPs group exhibited a significant decrease in NLRP3, ASC, and Casp1 gene expression compared to the SCI group (p < 0.0001). The findings indicated a significant decrease in the NLRP3, ASC, and Casp1 protein level between the Qu/BSA/ASCS group and the SCI group (p < 0.0001). Moreover, treatment with ASCS containing either blank BSA (B/BSA) NPs or Qu/BSA NPs effectively promoted functional recovery via increasing the amount of nestin- and glial fibrillary acidic protein (GFAP)-positive cells in the site of injury. Notably, Qu/BSA/ASCS exhibited superior outcomes compared to B/BSA/ASCS. Overall, the combination of ASCS with the Qu delivery system presents a promising therapeutic approach for SCI by inhibiting inflammatory responses and promoting neuroregeneration, leading to the restoration of motor function in animals. This study demonstrates the potential of utilizing biomaterials and NPs to enhance the effectiveness of SCI treatment. Note: Graphic abstract was designed with Biorender (https://biorender.com/). [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION The widespread use of quercetin is limited by its instability, low solubility and poor oral bioavailability. Encapsulation of quercetin using a nanoparticle delivery system is an effective way to overcome these drawbacks.The effect of the molecular weight (Mw) of chitosan (CS) (100, 200, 500 and 1000 kDa) on quercetin‐loaded chitosan nanoparticles (QCNPs) was investigated. The structure, stability, release properties and antioxidant activities of the nanoparticles (QCNP‐10, QCNP‐20, QCNP‐50 and QCNP‐100) were assessed. Particle size of QCNPs decreased and polydispersity index increased with the increasing Mw of CS. The main forces involved in the formation of QCNPs were hydrogen bonding and hydrophobic interaction. X‐ray diffraction verified that quercetin was loaded into CS nanoparticles. The photostability and thermal stability of QCNPs increased with increasing Mw of CS. QCNP‐100 exhibited the lowest release rate in a mixture of water and anhydrous ethanol. The antioxidant activities of QCNPs were enhanced with increasing Mw of CS, and QCNP‐100 possessed the highest antioxidant activities, which might be relevant to its smallest particle size.Overall, these results revealed that the Mw of CS affected the properties of QCNPs, and QCNP‐100 possessed the smallest particle, best stability, lowest release rate and highest antioxidant activities. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC. [ABSTRACT FROM AUTHOR]

1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit −8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated. 2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml. 3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level. 4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes. [ABSTRACT FROM AUTHOR]

In this work, carbon dots with green fluorescence were prepared by one-step hydrothermal reaction using corn stover as a carbon source. The carbon dots prepared under the optimal synthesis conditions had a spherical morphology with an average particle size of 2.07 ± 0.48 nm, and their fluorescence quantum yield reached 37.4%. The effects of various metal ions and organic small molecules on the fluorescence intensity of carbon dots were tested. The results showed that only quercetin caused a strong fluorescence quench of carbon dots, which were constructed as highly selective quercetin fluorescent probes based on the inner filter effect and the static quenching effect. The carbon dots quenched by quercetin exhibited high sensitivity for a fluorescence quench process, the quercetin concentration and the difference in fluorescence intensity of carbon dots (F0/F) showed linear relationship between two variables. For low the quercetin concentration was 10 ∼ 100 µmol·L−1, the standard curve was F0/F = 0.0078X + 1.08 (R2=0.9943); while the quercetin concentration was 100 ∼ 200 µmol·L−1, the standard curve was F0/F = 0.015X + 0.341 (R2=0.9937), and its limit of detection was 6.41 µmol·L−1. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI. [ABSTRACT FROM AUTHOR]