Targeting colorectal cancer using dietary flavonols.

Colorectal cancer is among the well-known forms of cancer and a prominent cause of cancer demises worldwide. In vitro experiments reinforced by animal studies, as well as epidemiological studies of human colorectal cancer propose that the growth of this disease can be moderated by eating aspects. Dietary intake including green vegetables and fruits may result in the reduction of colon cancer chances. The finding suggests that the combinations of dietary nutrients may deliver additive or synergistic effects and might be a powerful method to avoid or eradicate colon cancer beginning and/or development. Flavonols are one of the most widespread dietary nutrients of the polyphenols-flavonoids and major constituent of Allium and Brassicaceae vegetables. Flavonols present in vegetables of Allium and Brassicaceae family are kaempferol, myricetin, quercetin, and isorhamnetin. These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer. The objective of this review is to summarize the role of flavonols obtained from dietary sources in the prevention and treatment of colorectal cancer.

Quercetin may reduce the risk of developing the symptoms of COVID-19.

Objective: Recent evidence reported that some dietary compounds like quercetin and apigenin as the most well-known flavonoids with anti-inflammatory effects may inhibit SARS-CoV-2 main protease. The hypothesis of the promising effects and possible mechanisms of action of quercetin against COVID-19 were assessed in this article. Materials and Methods: Related papers on the inhibitory effects of quercetin against COVID-19 were collected using the following search strategy: "corona or coronavirus or COVID or COVID-19 or viral or virus" AND "nutrient or flavonoid or Quercetin". Results: The findings indicated that quercetin can be considered an effective agent against COVID-19 because of its SARS-CoV-2 main protease and RNA-dependent RNA polymerase inhibitory effects. In addition, quercetin may attenuate angiotensin-converting enzyme-2 (ACE-2) receptors leading to a reduction of SARS-CoV-2 ability to enter host cells. Moreover, the antiviral, anti-inflammatory, and immunomodulatory activities of quercetin have been frequently reported. Conclusion: Quercetin may be an effective agent for managing the complications of COVID-19. Further longitudinal human studies are warranted.

Quercetin as one of the most abundant represented biological valuable plant components with remarkable chemoprotective effects - A review.

As a consequence of environmental quality changes as well as changes in our population's lifestyle, there is rapidly increasing variability and many so-called lifestyle disorders, allergies, and food intolerances (also known as non-allergic food hypersensitivity). Unhealthy eating practices, an inappropriate food composition with an excessive energy intake, a high intake of saturated fats, simple sugars, and salt, as well as an inadequate intake of fibre, vitamins, and substances with preventive effects (such as antioxidants), are some of the factors causing this detrimental phenomenon. Enhanced consumption of plant foods rich in valuable secondary metabolites such as phenolic acids and flavonoids with the benefit on human health, food research focused on these components, and production of foods with declared higher content of biologically active and prophylactic substances are some ways how to change and improve this situation. A unique class of hydroxylated phenolic compounds with an aromatic ring structure are called flavonoids. One unique subclass of flavonoids is quercetin. This phytochemical naturally takes place in fruits, vegetables, herbs, and other plants. Quercetin and its several derivates are considered to be promising substances with significant antidiabetic, antibacterial, anti-inflammatory, and antioxidant effects, which could also act preventively against cardiovascular disease, cancer, or Alzheimer's disease.

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Objective: This study aims to systematically evaluate the protective role of quercetin (QCT), a naturally occurring flavonoid, against oxidative damage in human endometrial stromal cells (HESCs) induced by hydrogen peroxide (H2O2). Oxidative stress, such as that induced by H2O2, is known to contribute significantly to cellular damage and has been implicated in various reproductive health issues. The study is focused on investigating how QCT interacts with specific molecular pathways to mitigate this damage. Special attention was given to the p38 MAPK/NOX4 signaling pathway, which is crucial to the regulation of oxidative stress responses in cellular systems. By elucidating these mechanisms, the study seeks to confirm the potential of QCT not only as a protective agent against oxidative stress but also as a therapeutic agent that could be integrated in treatments of conditions characterized by heightened oxidative stress in endometrial cells. Methods: I n vitro cultures of HESCs were treated with QCT at different concentrations (0, 10, 20, and 40 µmol/L) for 24 h to verify the non-toxic effects of QCT on normal endometrial cells. Subsequently, 250 µmol/L H2O2 was used to incubate the cells for 12 h to establish an H2O2-induced HESCs injury model. HESCs were pretreated with QCT for 24 h, which was followed by stimulation with H2O2. Then, CCK-8 assay was performed to examine the cell viability and to screen for the effective intervention concentration. HESCs were divided into 3 groups, the control group, the H2O2 model group, and the H2O2+QCT group. Intracellular levels of reactive oxygen species (ROS) were precisely quantified using the DCFH-DA fluorescence assay, a method known for its accuracy in detecting and quantifying oxidative changes within the cell. The mitochondrial membrane potential was determined by JC-1 staining. Annexin Ⅴ/PI double staining and flow cytometry were performed to determine the effect of QCT on H2O2-induced apoptosis of HESCs. Furthermore, to delve deeper into the cellular mechanisms underlying the observed effects, Western blot analysis was conducted to measure the expression levels of the critical proteins involved in oxidative stress response, including NADPH oxidase 4 (NOX4), p38 mitogen-activated protein kinase (p38 MAPK), and phosphorylated p38 MAPK (p-p38 MAPK). This analysis helps increase understanding of the specific intracellular signaling pathways affected by QCT treatment, giving special attention to its potential for modulation of the p38 MAPK/NOX4 pathway, which plays a significant role in cellular defense mechanisms against oxidative stress. Results: In this study, we started off by assessing the toxicity of QCT on normal endometrial cells. Our findings revealed that QCT at various concentrations (0, 10, 20, and 40 µmol/L) did not exhibit any cytotoxic effects, which laid the foundation for further investigation into its protective roles. In the H2O2-induced HESCs injury model, a significant reduction in cell viability was observed, which was linked to the generation of ROS and the resultant oxidative damage. However, pretreatment with QCT (10 µmol/L and 20 µmol/L) significantly enhanced cell viability after 24 h (P<0.05), with the 20 µmol/L concentration showing the most substantial effect. This suggests that QCT can effectively reverse the cellular damage caused by H2O2. Furthermore, the apoptosis assays demonstrated a significant increase in the apoptosis rates in the H2O2 model group compared to those in the control group (P<0.01). However, co-treatment with QCT significantly reversed this trend (P<0.05), indicating QCT's potential protective role in mitigating cell apoptosis. ROS assays showed that, compared to that in the control group, the average fluorescence intensity of ROS in the H2O2 model group significantly increased (P<0.01). QCT treatment significantly reduced the ROS fluorescence intensity in the H2O2+QCT group compared to the that in the H2O2 model group, suggesting an effective alleviation of oxidative damage (P<0.05). JC-1 staining for mitochondrial membrane potential changes revealed that compared to that in the control, the proportion of cells with decreased mitochondrial membrane potential significantly increased in the H2O2 model group (P<0.01). However, this proportion was significantly reduced in the QCT-treated group compared to that of the H2O2 model group (P<0.05). Finally, Western blot analysis indicated that the expression levels of NOX4 and p-p38 MAPK proteins were elevated in the H2O2 model group compared to those of the control group (P<0.05). Following QCT treatment, these protein levels significantly decreased compared to those of the H2O2 model group (P<0.05). These results suggest that QCT may exert its protective effects against oxidative stress by modulating the p38 MAPK/NOX4 signaling pathway. Conclusion: QCT has demonstrated significant protective effects against H2O2-induced oxidative damage in HESCs. This protection is primarily achieved through the effective reduction of ROS accumulation and the inhibition of critical signaling pathways involved in the oxidative stress response, notably the p38 MAPK/NOX4 pathway. The results of this study reveal that QCT's ability to modulate these pathways plays a key role in alleviating cellular damage associated with oxidative stress conditions. This indicates not only its potential as a protective agent against cellular oxidative stress, but also highlights its potential for therapeutic applications in treating conditions characterized by increased oxidative stress in the endometrium, thereby offering the prospect of enhancing reproductive health. Future studies should explore the long-term effects of QCT and its clinical efficacy in vivo, thereby providing a clear path toward its integration into therapeutic protocols.

Effect of co-administration of gallic acid and quercetin or gallic acid and rutin on impaired spermatogenesis and oxidative damage in a busulfan-treated rat model.

Gallic acid (GAL), rutin (RUT), and quercetin (QUE) are common antioxidant agents in fruits and vegetables with intriguing pharmacological effects. In the present study, we compared the therapeutic outcomes of GAL + QUE in comparison with GAL + RUT co-treatment in a busulfan (BUS) model of testicular injury in Wistar rats. BUS (4 mg kg-1 body weight (b.w) was injected intraperitoneally daily for 4 days. GAL + RUT or GAL + QUE (20 mg kg-1 b. w) was delivered by oral gavage for 52 days. Examination of the testes of BUS-treated rats both biochemically and under light microscopy revealed an increased level of lipid peroxidation, DNA fragmentation, glutathione-S-transferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and acid phosphatase with a concomitant decrease in the level of antioxidants: glutathione, ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, suggesting testicular injury. Tissue sections confirmed the testicular injury-induced by BUS, including diminished spermatogenesis score index, tubular diameter, gonado-somatic index, testis weight, epithelia thickness and higher percentage of aberrant tubules. GAL + QUE co-administration had better recovery effects than GAL + RUT on the biochemical markers and protected against BUS-induced testicular damage. GAL + QUE treatment regimen has better capacity to maintain the antioxidant capacity of the testes and is more potent at reducing BUS-induced oxidative damage compared to GAL + RUT.

Treatment of bone-cartilage defects with dual-layer tissue-engineered scaffolds loaded with icariin and quercetin.

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

DFT simulated Quercetin imprinted polymer: Selective recovery of Quercetin from onion solid waste.

Onion peels (OP) are byproduct of food processing industries that poses economic and environmental challenges. However, being rich source of bioactive compounds like Quercetin (Qt), a polyphenolic antioxidant with potential health benefits, harnessing value from such waste can imbibe sustainable practices and protect environment. With this view, the present study targets selective recovery of Qt from OP waste using rationally designed molecularly imprinted polymer (MIP). Density Functional Theory (DFT) was used for the theoretical selection of the best conformer of Qt (template), methacrylic acid (MAA) as functional monomer, ratio of Qt-MAA for getting stable pre-polymerization complex, and to avoid hit and trial experiments. The theoretical results were validated experimentally by synthesizing MIP/ control polymer (NIP) using MAA as functional monomer, EGDMA as a cross-linker and AIBN as initiator. Synthesized MIP/NIP were characterized using various characterization techniques to confirm successful imprinting. Prepared MIP and NIP could effectively rebind the Qt molecule with binding capacity of 46.67 and 20.89 mg g-1 respectively. Furthermore, synthesized MIP could selectively recover 62.81 % of Qt from 1 g of dry onion peel powder. This study can be effectually used for sustainable recovery of Qt in large scale for various foods, cosmetic and pharmaceutical applications.

Liposomal quercetin: A promising strategy to combat hepatic insulin resistance and inflammation in type 2 diabetes mellitus.

In type 2 diabetes mellitus, hepatic insulin resistance is intricately associated with oxidative stress and inflammation. Nonetheless, the lack of therapeutic interventions directly targeting hepatic dysfunction represents a notable gap in current treatment options. Flavonoids have been explored due to their potential antidiabetic effects. However, these compounds are associated with low bioavailability and high metabolization. In the present study, four flavonoids, kaempferol, quercetin, kaempferol-7-O-glucoside and quercetin-7-O-glucoside, were studied in a cellular model of hepatic insulin resistance using HepG2 cells. Quercetin was selected as the most promising flavonoid and incorporated into liposomes to enhance its therapeutic effect. Quercetin liposomes had a mean size of 0.12 µm, with an incorporation efficiency of 93 %. Quercetin liposomes exhibited increased efficacy in modulating insulin resistance. This was achieved through the modulation of Akt expression and the attenuation of inflammation, particularly via the NF-κB pathway, as well as the regulation of PGE2 and COX-2 expression. Furthermore, quercetin liposomes displayed a significant advantage over free quercetin in attenuating the production of reactive pro-oxidant species. These findings open new avenues for developing innovative therapeutic strategies to manage diabetes, emphasizing the potential of quercetin liposomes as a promising approach for targeting both hepatic insulin resistance and associated inflammation.

Effects of Micellar Quercetin Supplementation on Growth Performance, Nutrient Digestibility, Fecal Microbiota, Meat Quality, and Physiological Status in Broiler Chickens.

This study investigated the impacts of micellar quercetin (MQ) supplementation on growth performance, meat stability, excreta gas emissions, and physiological status. During a 35-day trial, 640 Ross 308 broilers were utilized. These birds were one day old, with an average initial body weight of 43.34 ± 1.43 g. They were randomly distributed across four experimental diets, each consisting of 10 replicate pens with 16 chicks per pen. The diets included the following: control (CON) with 0% micellar quercetin (MQ), TRT1 with 0.025% MQ, TRT2 with 0.050% MQ, and TRT3 with 0.100% MQ. The results indicate that broilers fed diets with increasing levels of MQ exhibited significantly higher body weight gains (BWGs) compared to the control group (p < 0.05). There was a clear linear increase in the breast muscle percentage with higher levels of quercetin supplementation (p < 0.05), while the breast color remained consistent across all groups (p > 0.05). Both cooking loss and drip loss exhibited a linear decrease as MQ levels in the diet increased (p < 0.05). The level of aspartate aminotransferase (AST) tended to decrease with higher MQ levels. Thyroxine (T4) and lymphocyte levels also showed a linear increase with increasing MQ dosage in the diet (p < 0.05). However, no significant effects were observed on nutrient digestibility, gas emissions, or fecal microbial components (Lactobacillus, E. coli, and Salmonella) with higher levels of MQ supplementation (p > 0.05). In conclusion, augmenting quercetin levels in the diet positively influenced the BWG, breast muscle development, and meat quality parameters such as cooking loss and drip loss, with beneficial effects on blood profiles.

Aspects of quercetin stability and its liposomal enhancement in yellow onion skin extracts.

Quercetin is a flavonoid that occurs in many types of fruit and vegetables and is stable for no longer than 4.5 h in the investigated pH range (6.0-8.0), even at 4 °C in the dark. At higher temperatures, the degradation/oxidation process is much faster. Simple but effective proliposomal encapsulation was used to protect the quercetin from environmental conditions such as pH. With this approach, 65 to 90% of pure quercetin and quercetin-rich onion extract was kept after >60 days under conditions that favoured its oxidation (pH 7.4). In addition, the encapsulated quercetin decreases the lipid peroxidation induced by pulsed UV light by >50%. At a mass ratio of 1:100 quercetin to lipids (w/w), the liposomes remained intact in solutions for six months. Quercetin in lipid bilayers simultaneously protects the unsaturated lipids from peroxidation.

Evaluation of quercetin as a potential cytoprotector against acetaldehyde using the cultured hepatocyte model with aldehyde dehydrogenase isozyme deficiency.

Protective effect of quercetin against acetaldehyde was evaluated using the cultured hepatocyte models with aldehyde dehydrogenase (ALDH) isozyme deficiency (aldh2-kd and aldh1a1-kd). The quercetin-induced cytoprotection against acetaldehyde in the ALDH1A1-deficient mutant (aldh1a1-kd) was weaker than that in wild type. Furthermore, quercetin did not enhance the ALDH activity in aldh1a1-kd cells, suggesting that ALDH1A1 is involved in the quercetin-induced cytoprotection.

Preparation, characterization and antioxidant and anticancerous potential of Quercetin loaded ß-glucan particles derived from mushroom and yeast.

ß-glucans are polysaccharides found in the cell walls of various fungi, bacteria and cereals. ß-glucan have been found to show various kinds of anti-inflammatory, antimicrobial, antidiabetic antioxidant and anticancerous activities. In the present study, we have isolated ß-glucan from the baker's yeast Saccharomyces cerevisiae and white button mushroom Agaricus bisporus and tested their antioxidant potential and anticancerous activity against prostate cancer cell line PC3. Particles were characterized with zeta sizer and further with FTIR that confirmed that the isolated particles are ß-glucan and alginate sealing made slow and sustained release of the Quercetin from the ß-glucan particles. Morphological analysis of the hollow and Quercetin loaded ß-glucan was performed with the SEM analysis and stability was analyzed with TGA and DSC analysis that showed the higher stability of the alginate sealed particles. Assessments of the antioxidant potential showed that Quercetin loaded particles were having higher antioxidant activity than hollow ß-glucan particles. Cell viability of the PC3 cells was examined with MTT assay and it was found that Quercetin loaded alginate sealed Agaricus bisporus derived ß-glucan particles were having lowest IC50. Further ROS generation was found to increase in a dose dependent manner. Apoptosis detection was carried out with Propidium iodide and AO/EtBr staining dye which showed significant death in the cells treated with higher concentration of the particles. Study showed that particles derived from both of the sources were having efficient anticancer activity and showing a dose dependent increase in cell death in PC3 cells upon treatment.

Quercetin in Oncology: A Phytochemical with Immense Therapeutic Potential.

Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers.

Quercetin alleviates inflammation induced by porcine reproductive and respiratory syndrome virus in MARC-145 cells through the regulation of arachidonic acid and glutamine metabolism.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe inflammatory response, respiratory disease and sow reproductive failure. Quercetin is among the widely occurring polypheno found abundantly in nature. Quercetin has anti-inflammatory, anti-oxidative and anti-viral properties. OBJECTIVES: This study aimed to explore the effect and mechanism of quercetin on PRRSV-induced inflammation in MARC-145 cells. METHODS: Observing the cytopathic effect and measurements of inflammatory markers in MARC-145 cells collectively demonstrate that quercetin elicits a curative effect on PRRSV-induced inflammation. Liquid chromatography-mass spectrometry was further used for a non-targeted metabolic analysis of the role of quercetin in the metabolic regulation of PRRSV inflammation in MARC-145 cells. RESULTS: It was shown that quercetin attenuated PRRSV-induced cytopathy in MARC-145 cells. Quercetin treatment inhibited PRRSV replication in MARC-145 cells in a dose-dependent manner. We also found that quercetin inhibited PRRSV-induced mRNA expression and secretion levels of tumour necrosis factor-α, interleukin 1ß and interleukin 6. Metabolomics analysis revealed that quercetin ameliorated PRRSV-induced inflammation. Pathway analysis results revealed that PRRSV-induced pathways including arachidonic acid metabolism, linoleic acid, glycerophospholipid and alanine, aspartate and glutamate metabolism were suppressed by quercetin. Moreover, we confirmed that quercetin inhibited the activation of NF-κB/p65 pathway, probably by attenuating PLA2, ALOX and COX mRNA expression. CONCLUSIONS: These results provide a crucial insight into the molecular mechanism of quercetin in alleviating PRRSV-induced inflammation.

New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Novel role of Quercetin in ameliorating metabolic syndrome via VDR mediated activation of adiponectin/AdipoR2 signaling.

A sedentary lifestyle and physical inactivity leads to metabolic syndrome-associated comorbidities involving abdominal obesity, type 2 diabetes, hyperlipidaemia associated Cardiovascular Diseases (CVDs), and Metabolic dysfunction-associated fatty liver disease (MAFLD). In this study, we evaluated the novel hepato/cardio/adipo-protective role of Quercetin via Vitamin D Receptor, and elucidated its underlying mechanisms in reducing lipotoxicity, inflammation and fibrosis in high calorie diet induced metabolic syndrome. Male Swiss albino mice were fed with western diet and sugar water for multiple time intervals. Anti-lipotoxicity, anti-inflammatory, and anti-fibrotic effect of Quercetin was assessed by Oil Red O, H&E and TMS staining at different time points. The lipid profile, mRNA expression of inflammatory markers (TNF- α, IL-1ß, IL-6 and MCP-1), fibrotic markers (α-SMA, COL1A1, COL1A2), adiponectin, AdipoR2, and VDR expression levels were measured from RNA pools of adipose, liver and heart tissues. Also, lipid-lowering and anti-steatohepatitic effects of Quercetin was assessed using mouse 3T3-L1 adipocytes, rat H9c2 cardiac cells, and human HepG2 hepatocytes. Our results indicate that, western diet fed mice with Quercetin ameliorated lipid profile and lipotoxicity. Histopathological examination and gene expression data revealed that Quercetin reduced hepatic and cardiac inflammation and fibrosis-associated markers. Interestingly, Quercetin treatment increased the serum levels of adiponectin and mRNA expressions of AdipoR2 and VDR. In-vitro experiments revealed the reduction in lipid accumulation of 3T3-L1 and fatty-acid-treated hepatic and cardiac cells following Quercetin treatment. These findings indicate that Quercetin exhibits a protective role on multiple organs through VDR activation and subsequent Adipo/AdipoR2 signaling in metabolic syndrome associated obesity, hepatic injury, and cardiac dysfunction.

The role of quercetin in ameliorating bleomycin-induced pulmonary fibrosis: insights into autophagy and the SIRT1/AMPK signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. METHODS: Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. RESULTS: Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. CONCLUSION: This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.

Quercetin ameliorates atherosclerosis by inhibiting inflammation of vascular endothelial cells via Piezo1 channels.

BACKGROUND: Natural antioxidants, exemplified by quercetin (Qu), have been shown to exert a protective effect against atherosclerosis (AS). However, the precise pharmacological mechanisms of Qu also remain elusive. PURPOSE: Here, we aimed to uncover the anti-atherosclerotic mechanisms of Qu. METHODS/STUDY DESIGNS: The inflammatory cytokine expression, activity of NLRP3 inflammasome and NF-κB, as well as mechanically activated currents and intracellular calcium levels were measured in endothelial cells (ECs). In addition, to explore whether Qu inhibited atherosclerotic plaque formation via Piezo1 channels, Ldlr-/- and Piezo1 endothelial-specific knockout mice (Piezo1△EC) were established. RESULTS: Our findings revealed that Qu significantly inhibited Yoda1-evoked calcium response in human umbilical vein endothelial cells (HUVECs), underscoring its role as a selective modulator of Piezo1 channels. Additionally, Qu effectively reduced mechanically activated currents in HUVECs. Moreover, Qu exhibited a substantial inhibitory effect on inflammatory cytokine expression and reduced the activity of NF-κB/NLRP3 in ECs exposed to ox-LDL or mechanical stretch, and these effects remained unaffected after Piezo1 genetic depletion. Furthermore, our study demonstrated that Qu substantially reduced the formation of atherosclerotic plaques, and this effect remained consistent even after Piezo1 genetic depletion. CONCLUSION: These results collectively provide compelling evidence that Qu ameliorates atherosclerosis by inhibiting the inflammatory response in ECs by targeting Piezo1 channels. In addition, Qu modulated atherosclerosis via inhibiting Piezo1 mediated NFκB/IL-1ß and NLRP3/caspase1/ IL-1ß axis to suppress the inflammation. Overall, this study reveals the potential mechanisms by which natural antioxidants, such as Qu, protect against atherosclerosis.

Quercetin as the primary xanthine oxidase inhibitor compound in Maclura tricuspidata leaf.

Maclura tricuspidata (MT) leaf demonstrated various health benefits, notably the inhibition of xanthine oxidase (XOD) activity, which is crucial in the management of hyperuricaemia and many diseases related to oxidative stress. This study aimed to identify the primary compound responsible for this inhibitory effect. Through a systematic investigation, MT leaf extracts were subjected to solvent-solvent partitioning using ethyl acetate, n-hexane, n-butanol, and dichloromethane. Further purification involved adsorption and desorption using Amberlite XAD-2 resin, followed by column chromatography on Silica Gel and Sephadex LH-20. The purified compounds were analysed using UPLC-QTOF-MS coupled with NMR spectroscopy. Our findings identified quercetin, a phenolic compound, as the most significant inhibitor of XOD activity in MT leaf, with an IC50 value of 212.92 µg/ml. This is the first report of purifying and identifying a single compound responsible for XOD inhibition in MT.

RGD-modified ZIF-8 nanoparticles as a drug carrier for MR imaging and targeted drug delivery in myocardial infarction.

Aim: A multifunctional nanoplatform has been developed to enhance the targeting capability and biosafety of drug/siRNA for better diagnosis and treatment of myocardial infarction (MI). Materials & methods: The nanoplatform's chemical properties, biodistribution, cardiac magnetic resonance imaging (MRI) capabilities, therapeutic effects and biocompatibility were investigated. Results: The nanoplatform exhibited MI-targeting properties and pH-sensitivity, allowing for effective cardiac MRI and delivery of drugs to the infarcted myocardium. The GCD/Qt@ZIF-RGD demonstrated potential as a reliable MRI probe for MI diagnosis. Moreover, the GCD/si-SHP1/Qt@ZIF-RGD effectively suppressed SHP-1 expression, increased pro-angiogenesis gene expression and reduced cell apoptosis in HUVECs exposed to hypoxia/reoxygenation. Conclusion: Our newly developed multifunctional drug delivery system shows promise as a nanoplatform for both the diagnosis and treatment of MI.

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