Quercetin Research Articles

Enhancing osteogenic properties with gelatin/chitosan hydrogel encapsulating lithium-coated titanium oxide hollow sphere particles loaded with quercetin.

Metallic oxides especially lithium and titanium oxides are well known for their osteogenic properties. When combined in the right proportions, metallic oxides can have an even greater impact. However, releasing ions from oxides can lead to oxidative stress, which is harmful to cell growth. By reducing oxidative stress, we can enhance these ions' therapeutic and bone-forming properties. In our study, we have developed a novel combination of titanium oxide coated with lithium oxide to release ions simultaneously. We engineered hollow sphere titanium oxide particles to carry Quercetin (QC), a natural antioxidant. These particles were then incorporated into a gelatin/chitosan-based hydrogel, which was further functionalized with carbon nanotubes (CNTs) which induced conductivity and improved mechanical properties. In drug release experiments, we found that QC was released steadily from the hydrogel, in contrast to a control group where the drug was simply mixed in with hydrogel indicating the significance of asecondary carrier. Additionally, our cytotoxicity tests demonstrated the importance of delivering QC alongside lithium and titanium ions, as this combination reduced toxicity and enhanced bone-forming activity. Finally, our study showed that the hydrogel containing drug-loaded hollow sphere particles was able to promote bone formation, as evidenced by osteogenic differentiation studies. This innovative approach holds promise for improving bone regeneration therapies in the future.&#xD.

Quercetin alleviates endothelial dysfunction in preeclampsia by inhibiting ferroptosis and inflammation through EGFR binding

Preeclampsia (PE) is a pregnancy-specific complication and there remains no effective treatment. Given the limitations on medication use during pregnancy, exploring natural, safe, and effective drugs for PE is worthwhile. We investigate the causal relationship between ferroptosis, inflammation, and PE, and determine the protective effects of quercetin (QCT), a representative compound that is classified as a flavanol, against endothelial dysfunction. Then, the target of QCT is predicted and verified. The prophylactic addition of a low dose of QCT rescues endothelial dysfunction, aiding in endothelial repair. Furthermore, QCT alleviates PE-like maternal manifestations and endothelial dysfunction in the placenta of the selective reduced uteroplacental perfusion (sRUPP) rat model through binding to the epidermal growth factor receptor (EGFR). The potential applications of QCT are expanded, offering the possibility of further development as a safe and effective preventive molecule for PE.

Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies.

Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness.

Modulatory effect of quercetin on aspirin-induced hepatoxicity in Wistar rats

Objectives: Aspirin, also known as acetylsalicylic acid, is a non-steroidal anti-inflammatory drug medication. Aspirin has been shown to have a wide range of pharmacological effects, such as antipyretic, antiplatelet and analgesic effects. Although there is little known about how aspirin causes hepatotoxicity at the cellular level, this does happen and there is a need to look into some hepatoprotective remedies. The aim of this study was to assess how quercetin (QE) affects aspirin-induced hepatotoxicity in Wistar rats. Materials and Methods: Thirty-five male adult Wistar rats divided into seven experimental groups were used in this study. These groups received different treatments: Some were given varying concentrations of QE (30 mg/kg and 60 mg/kg), while others received aspirin (50 mg/kg). In addition, there were control groups that did not receive either aspirin or QE, with normal saline and corn oil being administered instead. The administration of treatments lasted for 30 days, after which the experiment was concluded, and the rats’ livers were removed for histological examination. Simultaneously, blood serum samples were collected for the biochemical analysis of liver enzyme markers. The level of significance was set at 0.05, and the data collected was analysed using the Statistical Package for the Social Sciences version 29. Results: It was found that aspirin increased the level of liver enzyme markers in the serum after 30 days of administration resulting from damage to the liver cells, this effect was most significant at an aspirin concentration of 50 mg/kg and QE at a concentration of 60 mg/kg was most effective in exhibiting hepatoprotective potentials. Conclusion: The results suggest that aspirin 50 mg/kg could be hepatotoxic due to the lessening of antioxidant effects, and QE has a modulating effect on aspirin-induced toxicity.

Quercetin inhibits platelet activation and ER-stress mediated autophagy in response to extracellular histone.

Cellular histones are DNA-binding nuclear proteins involved in chromatin remodelling and regulation of gene expression. However, extracellular histones act as damage-associated molecular patterns (DAMPs) and contribute to multiorgan damage in conditions with sepsis and diseases with acute critical illnesses. Alongside, histones are associated with thrombocytopenia due to dysfunctional platelets that regulate hemostasis and thrombosis. There is no drug available to prevent histone-induced platelet toxicity. Therefore, we for the first time examined quercetin (QUE) as a novel therapeutic to protect histone-induced platelet toxicity. To delineate how histones induce platelet toxicity and investigate the protective efficacy of quercetin (QUE), a natural dietary phytochemical. Histone-treated platelets were evaluated for platelet aggregation/activation markers, various autophagy-related signaling proteins, and cytotoxicity in vitro. For the inhibition study, QUE and other standard inhibitors were pre-treated before stimulation with histones. Further, we injected histones into mice in the presence or absence of QUE and evaluated the tail bleeding, lung toxicity, and circulatory platelet stress markers. Additionally, QUE-treated mice were challenged for histone-primed Collagen-epinephrine-induced pulmonary thromboembolism. Extracellular histones induce platelet activation and aggregation by interacting with sialic acid in TLR1/2 or TLR4. Also, we have demonstrated for the first time that histones induce ER stress-mediated autophagy in platelets. QUE inhibited histone-induced platelet activation, aggregation, and ER-stress-mediated autophagy in response to histone treatment. Ex vivo experiments indicate that oral administration of QUE can safeguard platelets while concurrently mitigating their response to histone stimulation. In addition, quercetin increased the survival rates of histone-primed, collagen-epinephrine-induced acute pulmonary thromboembolism in mice. In summary, this study demonstrated the beneficial effect of QUE in protecting platelets with possible implications for addressing histone-accelerated pathologies.

Effects of Quercetin and Citrulline on Nitric Oxide Metabolites and Antioxidant Biomarkers in Trained Cyclists.

Quercetin (QCT) and citrulline (CIT) have been independently associated with improved antioxidant capacity and nitric oxide (NO) production, potentially enhancing cardiovascular function and exercise performance. This study aimed to evaluate the combined and independent effects of QCT and CIT supplementation on NO metabolites and antioxidant biomarkers in 50 trained cyclists undergoing a 20 km cycling time trial (TT). In a randomized, double-blind, placebo-controlled design, forty-two male and eight female trained cyclists were assigned to QCT + CIT, QCT, CIT, or placebo (PL) groups. Supplements were consumed twice daily for 28 days. Biochemical assessments included NO metabolites (nitrate/nitrite), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD) activity, and antioxidant capacity, measured pre- and post-TT. NO metabolites were significantly elevated post-supplementation (p = 0.03); however, no significant interaction effects were observed for NO metabolites, FRAP, SOD, or antioxidant capacity across the groups (p > 0.05). Post-hoc analyses revealed that QCT significantly reduced FRAP concentrations compared to PL (p = 0.01), while no significant changes in SOD or antioxidant capacity were found across any groups. These findings suggest that combined and independent QCT and CIT supplementation did not significantly improve these biomarkers, suggesting that baseline training adaptations, supplementation timing, and individual variability may influence the efficacy of these compounds in enhancing exercise performance and oxidative stress markers. The ergogenic efficacy of QCT + CIT on antioxidant-related markers remains inconclusive.

Drug in Drug: Quorum Sensing Inhibitor in Star-Shaped Antibacterial Polypeptides for Inhibiting and Eradicating Corneal Bacterial Biofilms.

Biofilm-related bacterial keratitis is a severe ocular infection that can result in drastic vision impairment and even blindness. However, the therapeutic efficiency of clinical antibiotic eyedrops is often compromised because the bacteria in the biofilms resist bactericide via the community genetic regulation, namely, bacterial quorum sensing. Herein, quercetin (QCT)-loaded star-shaped antibacterial peptide polymer (SAPP), QCT@SAPP, is developed based on a "drug" in a "drug" strategy for inhibiting and eradicating Pseudomonas aeruginosa biofilms on the cornea. The natural antibacterial peptide-mimic SAPP with the positively charged amphipathic structure not only enables QCT@SAPP to penetrate the biofilms readily but also selectively adheres to the highly negatively charged P. aeruginosa, releasing the loaded QCT into the bacteria to regulate quorum sensing by inhibiting lasI, lasR, rhlR, and rhlI. Thanks to its robust bactericidal ability from SAPP, QCT@SAPP can eliminate more than 99.99% of biofilms. Additionally, QCT@SAPP displayed outstanding performance in relieving ocular inflammation by significantly downregulating pro-inflammatory cytokines and profiting from scavenging reactive oxygen species by releasing QCT, which finally helps to restore visual function. In conclusion, QCT@SAPP, with good compatibility, exerts excellent therapeutic effects in a bacterial keratitis mice model, making it a promising candidate for controlling bacterial biofilm-induced infections, including bacterial keratitis.

Synergistic Inhibition of Breast Carcinoma Cell Proliferation by Quercetin and Sulforaphane via Activation of the ERK/MAPK Pathway.

In the contemporary era of drug discovery, herbal treatments have demonstrated an unparalleled ability to produce anticancer drugs. An important part of the therapy of cancer is the use of plants and their by-products via analogues, which alter the tumor microenvironment and several signaling pathways. The objective of the current investigation was to conclude the rate at which the herbal medications quercetin (QT) and sulforaphane (SFN) repressed the growth of breast carcinoma cells in MDA-MB-231 by preventing the ERK/MAPK signaling systems. The cells were assessed for several studies after being subjected to different concentrations (0-70 µM) of QT and SFN (QT + SFN) for duration of 24 h. We investigated the combination that QT + SFN generated cytotoxicity using the MTT assay. The DCFH-DA staining technique was utilized to assess ROS. The protein spectra of survival of cells, cell cycle progression, and apoptosis were evaluated employing flow cytometry and western blotting. The consequences illustrated that the relative cytotoxicity of QT and SFN was roughly 28.74 μM and 39.87 μM for MDA-MB-231 cells, respectively. Following the 24-h incubation period, MDA-MB-231 cells exhibit considerable cytotoxicity when QT and SFN are combined, with IC50 values of 19.48 μM. Moreover, MCF-7 and MDA-MB-231 cells treated with QT and SFN concurrently showed substantial production of ROS and increased apoptotic signals. Consequently, because QT + SFN inhibit the production of ERK/MAPK/JNK/p38-based control of proliferation and cell cycle-regulating proteins, it has been considered a chemotherapeutic medication. To determine the extent to which the co-treatment induces apoptosis, more in vivo study will be required before they can be used commercially.

The M1/M2 Macrophage Polarization and Hepatoprotective Activity of Quercetin in Cyclophosphamide-Induced Experimental Liver Toxicity.

Chemotherapy drugs may lead to hepatic injury, which is considered one of the limitations of these drugs. The aim of this study was to evaluate the effect of quercetin (QUE) on M1/M2 macrophage polarization and hepatoprotective effect in cyclophosphamide (CTX)-induced liver toxicity. Twenty-four mice were divided into four groups (Control, QUE, CTX, CTX + QUE). The CTX and CTX + QUE groups received 200mg/kg CTX. The animals in the QUE and CTX + QUE groups received 50mg/kg QUE. All animals were sacrificed, and serum and liver samples were used for laboratory analyses. Examinations indicated that CTX exposure led to disruption of liver functions and morphological degenerations. Tissue pro-apoptotic Bax and caspase 3, pro-inflammatory TNF-α and IL-1β, transcription factor NF-κB, and M1 macrophage polarization marker CD86 were upregulated significant (p<0.05) in this group. In addition, CTX exposure led to significantly (p<0.05) upregulation of the Bax/Bcl-2 mRNA ratio and DNA fragmentations. The PCNA-positive hepatic cell ratio and anti-apoptotic Bcl-2 expression are remarkably suppressed (p<0.05). Immunohistochemical analyses are also indicated that M2 macrophage polarization marker CD163 is slightly but remarkably (p<0.05) downregulated in the CTX group compared to the Control and QUE groups. The morphological and biochemical disruptions were alleviated in QUE-treated animals in the CTX + QUE group. Liver function test results, apoptosis, inflammatory, transcription factor NF-κB, regeneration/proliferation, and apoptotic index results in this group were similar (p>0.05) to the control and QUE groups. The M1 cell surface marker expression of CD86 is significantly (p<0.05) downregulated, and M2 macrophage polarization marker expression of CD163 is upregulated significantly (p<0.05) compared to the CTX group. This study indicates that QUE has the potential to downregulate CTX-induced hepatic injury and regulate M1/M2 macrophage polarization to the M2 side, which indirectly demonstrates activation of anti-inflammatory signalling and tissue repair.

Enhanced efficacy of quercetin and taxifolin encapsulated with pH-responsive injectable BSA hydrogel for targeting triple-negative breast cancer cells.

Quercetin (QUE) and Taxifolin (TAX) are natural flavonoids with diverse biological activities, holding promise for cancer treatment. However, their clinical application is limited by their poor solubility and bioavailability. Self-assembled bovine serum albumin (BSA) hydrogels have demonstrated biocompatibility and proteolytic stability, making them suitable platforms for drug delivery. The present study validated the anticancer efficacy of QUE, TAX, and DOX encapsulated in BSA hydrogel (QUE@ BSA hydrogel, TAX@ BSA hydrogel, and DOX@ BSA hydrogel), which exhibited 93.5, 90 and 91.2%% entrapment efficiency, respectively, and controlled release profiles with 90.8,95.8 and 90.8% drug release, respectively, at lower pH using MDA-MB 231 and MDA-MB 468 TNBC cell lines. Characterization by SEM, XRD, FT-IR and DLS revealed distinctive features of QUE@ BSA hydrogel, TAX@ BSA hydrogel, and DOX@BSA hydrogels, suggesting potential for targeted drug delivery. Further, investigations showed that separate treatment with QUE@BSA hydrogel, TAX@BSA hydrogel, and DOX@BSA hydrogel disrupted cell membrane integrity, akin to inducing cytotoxicity with IC50 of 12.90, 15.52 and 6.9μM, respectively, in MDA-MB 231 cells and 16.67, 19.16 and 5.2μM, respectively, in MDA-MB 468 cells. Moreover, they reduced mammosphere formation and cell migration. Additionally, they induced cell cycle arrest, reduced cell proliferation, and induced apoptosis in TNBC cells. They also induced ROS generation and ER stress, highlighting their potential to suppress TNBC progression. Overall, this study underscores the promise of QUE@ BSA hydrogel and TAX@BSA hydrogel as effective anticancer agents against TNBC cell lines in line with DOX@BSA hydrogel, offering controlled drug release and enhanced therapeutic outcomes.

Optimizing etodolac and quercetin loaded MSNs using taguchi design: an approach for enhancing drug loading efficiency.

The application of mesoporous silica nanoparticles (MSN) as a drug carrier system got immense attention in the past few years due to their exceptional high drug loading efficiency. However, the process of drug loading is quite challenging compared to other lipid-based drug delivery systems. Hence, the MSNs using different catalysts were synthesized, and their mesoporous material characteristic was confirmed by the type IV adsorption-desorption isotherm using BET analyzer. The effect of solvent selection and other process parameters (drug to MSNs ratio, period of loading, and stirring speed) on the loading of BCS class II and IV model drugs etodolac(ETD) and quercetin(QUR) respectively were investigated with the help of Taguchi DOE. The predicted value for the highest % drug loading was close to the experimental value(19.04 ± 0.50 % and 11.40 ± 0.18 % for ETD and QUR respectively). It was interesting to note, that the solvent selection had the highest impact on the drug loading of ETD into the MSNs, whereas for QUR this parameter was insignificant. Hence reflecting that a generalized procedure for the drug loading into the MSNs cannot be followed and had to be critically studied. Also, the loading of ETD and QUR into the MSNs improved the aqueous solubility (3.08 and 2.5 folds respectively). Further the in-vitro drug release properties were evaluated for ETD and QUR from MSNs in various drug release mediums to explore their release mechanism from MSNs using in vitro drug release kinetic modelling.

Impact of various vacuum degrees during grinding and on the quality characteristics of the onion: Color, antioxidant activities, quercetin, and quercetin glucoside compounds

Impact of various vacuum degrees during grinding and on the quality characteristics of the onion: Color, antioxidant activities, quercetin, and quercetin glucoside compounds

Antioxidant and cytotoxic activities of 2-oxo-1,2,3,4-tetrahydropyrimidines

Oxidative stress (OS) is an imbalance between ROS and antioxidants which is caused by increased synthesis and buildup of reactive oxygen species as well as a reduced ability to detoxify them. It contributes to the onset and progression of chronic inflammation, cancers, diabetes mellitus, atherosclerosis, Alzheimer’s disease, ocular disease, nephropathy, and premature aging. The molecules known as antioxidants contribute significantly to both the prevention and exaggeration of ailments. In the present study, heterocyclic ethyl esters of 2-oxo-1,2,3,4-tetrahydropyrimidines 1–25 were assessed for their antioxidant activity by employing two robust in vitro bioassays; superoxide anion, and DPPH radical scavenging assays. Cytotoxicity was also performed to evaluate the cytotoxicity on PC3 cells. Out of twenty-five, twenty-two compounds exhibited IC50 values in the range of 3.32 ± 0.08 – 167 ± 0.7 µM in superoxide anion assay. Compound 2 (IC50 = 3.32 ± 0.08 µM) remained the most potent as compared to quercetin dihydrate (IC50 = 94.1 ± 1.1 µM). Whereas, compound 10, possessing a catechol moiety was identified as an excellent dual radical scavenger. Hence, this study identified 2-oxo-1,2,3,4-tetrahydropyrimidines ethyl esters as non-cytotoxic, potent ROS scavengers that can be studied further to treat oxidative stress and related pathologies.

Spectrophotometric determination of quercetin using micelles of cetyltrimethylammonium bromide in a low ratio methanol–water mixture

A simple and achievable UV-Vis spectrophotometric method for the micro-quantitative determination of quercetin has been developed and validated. This method relies on the formation of supramolecular assemblies of quercetin (QR) and the cationic surfactant cetyltrimethylammonium bromide (CTAB) in a 5 % methanolic aqueous solution. In this solvent medium, CTAB in the presence of QR has a critical micelle concentration of 1.2·10-3 mol l-1 at 24 °C, determined through conductometry. Important analytical parameters such as wavelength, composition of methanol-water mixture, CTAB concentration (cCTAB), and pH were optimized. Under the optimum experimental conditions (l = 397 nm, 5 % methanol as solvent, cCTAB = 2.0·10-3 mol l-1, and pH = 6.0), Beer's law was valid for QR concentrations up to 16.9 mg ml-1. The Ringbom optimum QR concentration range was 1.0 - 16.9 mg ml-1. The method sensitivity was 2.03·104 l mol-1 cm-1 (the molar absorptivity) and 0.13 mg ml-1 (limit of detection). The applicability of the proposed method for quantifying QR in pharmaceutical formulations was demonstrated. Furthermore, the proposed UV-Vis spectrophotometric method was successfully applied to the reliably assay of QR, even in the presence of vitamin C.

Quercetin attenuates the symptoms of osteoarthritis in vitro and in vivo by suppressing ferroptosis via activation of AMPK/Nrf2/Gpx4 signaling.

Osteoarthritis (OA) is a common joint disorder involving the cartilage and other joint tissues. Quercetin (QCT) serves a protective role in the development of OA. However, to the best of our knowledge, the regulatory mechanisms of QCT in the progression of OA have not yet been fully elucidated. In order to mimic a model of OA in vitro, IL‑1β was used to stimulate chondrocytes. Furthermore, an in vivo animal model of OA was induced by anterior cruciate ligament transection (ACLT). 5‑Ethynyl‑2'‑deoxyuridine assays, TUNEL assays, ELISAs, western blotting and immunohistochemical assays were conducted to assess the chondroprotective properties of QCT in the development of OA. The results revealed that 100 µM QCT significantly promoted the proliferation, reduced the apoptosis and inflammation, and inhibited the extracellular matrix (ECM) degradation in IL‑1β‑stimulated chondrocytes. Additionally, QCT attenuated the IL‑1β‑induced ferroptosis of chondrocytes, as demonstrated by the reduced lipid reactive oxygen species and Fe2+ levels. Conversely, the inhibitory effects of QCT on the apoptosis and inflammatory responses were reversed by the activation of ferroptosis by erastin in IL‑1β‑stimulated chondrocytes. Furthermore, QCT significantly elevated the level of phosphorylated (p‑)5' AMP‑activated protein kinase (AMPK) and the levels of two negative regulators of ferroptosis [nuclear factor erythroid 2‑related factor 2 (Nrf2) and glutathione peroxidase 4 (Gpx4)] in IL‑1β‑stimulated chondrocytes. The AMPK inhibitor compound C notably reversed the promoting effects of QCT on phosphorylated‑AMPK, Nrf2 and Gpx4 expression in IL‑1β‑stimulated chondrocytes. Additionally, QCT markedly ameliorated the destruction and degradation of articular cartilage, and elevated the p‑AMPK, Nrf2 and Gpx4 levels in the mouse model of ACLT‑induced OA. Overall, the present study demonstrated that QCT inhibited the development of OA by suppressing ferroptosis via the activation of the AMPK/Nrf2/Gpx4 signaling pathway. These findings provide novel insights into the regulatory mechanisms of QCT for the treatment of patients with OA.

Molecular Signaling Pathways of Quercetin in Alzheimer's Disease: A Promising Arena.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and memory deficit. Even with extensive research and studies, presently, there is no effective treatment for the management of AD. Besides, most of drugs used in the treatment of AD did not avert the AD neuropathology, and the disease still in a progressive status. For example, acetyl cholinesterase inhibitors are associated with many adverse effects, such as insomnia and nightmares. As well, acetylcholinesterase inhibitors augment cholinergic neurotransmission leading to the development of adverse effects related to high acetylcholine level, such as salivation, rhinorrhea, vomiting, loss of appetite, and seizure. Furthermore, tacrine has poor bioavailability and causes hepatotoxicity. These commonly used drugs do not manage the original causes of AD. For those reasons, natural products were repurposed for the treatment of AD and neurodegenerative diseases. It has been shown that phytochemicals produce neuroprotective effects against the development and progression of neurodegenerative diseases by different mechanisms, including antioxidant and anti-inflammatory effects. Quercetin (QCN) has been reported to exert an effective neuroprotective effect against AD and other neurodegenerative diseases by lessening oxidative stress. In this review, electronic databases such as PubMed, Scopus, and Web of Science were searched for possible relevant studies and article linking the effect of QCN on AD. Findings from this review highlighted that many studies highlighted different mechanistic signaling pathways regarding the neuroprotective effect of QCN in AD. Nevertheless, the precise molecular mechanism of QCN in AD was not completely clarified. Consequently, this review aims to discuss the molecular mechanism of QCN in AD.

Quercetin Enhances 5-Fluorouracil-Driven Cytotoxicity Dose-Dependently in A375 Human Melanoma Cells.

Cutaneous melanoma (CM) represents a severe skin cancer with a rising incidence at present and limited treatment options. 5-Fluorouracil (5-FU) is widely used, including for CM; however, the innate resistance of this cancer to conventional therapy remains problematic. Quercetin (QUE) is a flavonoid that can sensitize cancer cells to antitumor agents such as 5-FU. However, the potential sensitization capability of CM cells to 5-FU has scarcely been determined, and is investigated herein. Therefore, A375 CM cells were tested in terms of their cell viability, cell confluence, and morphological changes. Their nuclear and cytoskeletal aspects, clonogenic potential, and in ovo properties were also followed. The results showed that the 50% inhibitory concentrations (IC50s) of 5-FU and QUE determined by a cell proliferation assay were 11.56 and 11.08 µM, respectively. The addition of QUE (10 µM) to 5-FU (5-50 µM) increased the cytotoxic potential. A significant decline in cell viability (up to 43.51%), the loss of cell confluence, chromatin condensation and nuclear dysmorphology, tubulin and F-actin constriction, and a suppressed clonogenic ability were noted. The QUE + 5-FU association was non-irritating to the chorioallantoic membrane and showed an antiangiogenic effect in ovo. Thus, our results highlight that combining QUE with 5-FU can enhance the cytotoxic effect of 5-FU in A375 melanoma cells and present a safe profile in ovo.

Sericin stabilized emulgel for improving therapeutic efficacy of quercetin in treatment of diabetic wound healing

Emulsion stability is vital for effectiveness, ensuring uniform distribution of droplets and preventing phase separation. Instability can lead to inconsistent performance and reduced therapeutic benefits. Thus, our research endeavors were directed toward the design and characterization of a sericin (SN) stabilized quercetin (QRN) emulgel (EG), specifically tailored for diabetic wound healing. Employing a two-factor, 3-level factorial design SN-stabilized QRN emulgel (QSEG) was prepared and the influence of varying percentages of olive oil and SN on zeta potential, globule size, and entrapment efficiency (%) was scrutinized. The optimized QRN emulgel (QSEG), composed of 10% oil and 5% SN (QSE-6), showcased a diminutive globule size of 809.2 ± 21.3 nm alongside an elevated zeta potential of −42.9 ± 3.79 mV. Submicron-sized spherical globules were observed without any signs of coalescence, confirmed by surface morphology analysis. FTIR showed compatibility, while DSC and XRD confirmed that QRN was amorphized and evenly dispersed within the emulgel. In-vitro scratch assays manifested reduced intercellular distances and wound closure, indicative of potent wound healing attributes of QSEG. QSEG demonstrated notable antibacterial efficacy against Escherichia coli (E. coli), with minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 3.125 ± 0.4 and 6.25 ± 1.2 μg/mL, respectively, surpassing that against Staphylococcus aureus (S. aureus). Cytotoxicity assays evidenced diminished toxicity toward fibroblast cells. Furthermore, in-vivo wound healing studies unveiled significant (p ˂ 0.001) enhancements with QSEG compared to QRN-treated and control groups. Our findings underscore SN’s role as a natural stabilizer, synergistically enhancing QSEG’s diabetic wound healing potential. Conclusively, QSEG emerges as a promising alternative to conventional diabetic wound healing treatments, offering inherent medicinal benefits.

Effects of Tithonia diversifolia Extract as a Feed Additive on Digestibility and Performance of Hair Lambs.

Animal production requires efficiency, safety and environmental sustainability. Bioactive compounds from tropical plants could modulate ruminal fermentation, providing an alternative method to antibiotic treatment and addressing concerns about antibiotic resistance. In this study, the aim was to determine the effects of Tithonia diversifolia extract (TDE) on performance, intake, digestibility and blood parameters [i.e., glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT)] in crossbreed sheep. The main biocompounds of the TDE include caffeic acid (CA), quercetin (QCT), luteolin (LT) and apigenin (AP). Experiment 1: An in vitro dry matter digestibility (IVDMD) study was conducted to determine the optimal inclusion levels. The IVDM values were 73.09a, 82.03b, 81.01b, 73.20a and 74.51a for the control, 5, 10, 15 and 20 g/kg for the DM treatments, respectively (R-Sq adj = 0.857). The levels of 5 and 10 g were selected for the in vivo experiment. Experiment 2: Twenty-eight male crossbred hair lambs were assigned to four treatments (n = 7): control, 20 mg monensin/day, 5 g TDE/day and 10 g TDE/day groups. No differences in animal performance were observed, including body weight and feed conversion (p > 0.05). The TDE at 10 g/day improved NDF digestibility) (61.32%) and reduced the ruminal acetate to propionate ratio. The total digestible nutrients (TDN) were higher in 10 g TDE treatment with 66.41% and the lowest acetate production (67.82%) (p = 0.042), and propionate production (21.07%) were observed. The TDE were safe at 5 g and 10 g/day for liver function and exhibited lower BUN levels suggesting an improvement in protein metabolism. TDE extract at 10 g/day (TDE10), showed improvements in total tract digestibility of NDF and reduced the ruminal acetate to propionate ratio. However, due to TDE10 reducing the DM intake, the improvements in digestibility and ruminal fermentation were not reflected in growth performance improvements.

Quercetin Alleviates Cardiac Fibrosis via Regulating the SIRT3 Signaling Pathway.

Cardiovascular diseases, exacerbated by cardiac fibrosis, are the leading causes of mortality. We aimed to determine the role of quercetin (QU) in cardiac fibrosis and the underlying mechanism. In this study, 8-week-old mice were subjected to either transverse aortic constriction (TAC) or sham surgery, then they were administered QU or saline. Thereafter, cardiac function and cardiac hypertrophy were accessed. In vitro, cardiac fibroblasts (CFs) were treated with angiotensin II (Ang II) with or without QU. Western blot, qPCR, EdU incorporation assay, and immunofluorescence staining analysis were used to investigate the molecular and cellular features. For the TAC mouse model, cardiac fibrosis was alleviated by QU. The study revealed that the trans-differentiation and proliferation of CFs promoted by Ang II would be reversed by QU in vitro. Mechanistically, QU exerted the anti-fibrotic effect by regulating the SIRT3/TGF-β/Smad3 signaling pathway. Quercetin protects against cardiac fibrosis by mediating the SIRT3 signaling pathway.