[Protective effect and mechanism of quercetin on acute liver injury induced by diquat poisoning in mice].

OBJECTIVE: To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. METHODS: Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. RESULTS: Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (µmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/ß-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/ß-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/ß-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/ß-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). CONCLUSIONS: QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

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 Modulates Ferroptosis via the SIRT1/Nrf-2/HO-1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model.

Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1ß-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1ß, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.

[Liposome co-delivery of quercetin and doxorubicin in inhibiting retinoblastoma by regulating epithelial-mesenchymal transition process].

Regulating the process of epithelial-mesenchymal transition(EMT) is an essential strategy to inhibit tumor growth and metastasis. This study is based on the EMT process of retinoblastoma and constructs quercetin(QUE) and doxorubicin(DOX) co-loaded liposome(QD Lipo) to investigate the therapeutic effect and mechanisms of combined QUE and DOX treatment on retinoblastoma. Single-factor experiments were conducted to optimize the prescription process of QD Lipo. Eventually, spherical particles with a diameter of(108.87±1.93) nm, a PDI of 0.13±0.02, and a Zeta potential of(-34.83±1.92) mV were obtained. The encapsulation rates of QUE and DOX were 96.20%±4.40% and 91.17%±4.41%, respectively. Y79 human retinoblastoma cells were used as an in vitro cellular model, and confocal microscopy demonstrated that QD Lipo could enhance Y79 uptake efficiency. The CCK-8 assay confirmed that the optimal combination therapy effect of QUE and DOX occurred at a mass ratio of 1∶1 to 1∶2. Flow cytometry showed that QD Lipo enhanced the induction of apoptosis in Y79 cells. Western blot analysis revealed that QD Lipo significantly reduced the expression of EMT pathway-related proteins vimentin and α-SMA. Fluorescence assays detected a significant decrease in ROS levels in Y79 cells after treatment with QD. These results indicated that liposomal co-delivery of QUE and DOX can enhance drug delivery efficiency to retinoblastoma cells, inhibit the EMT process in retinoblastoma by downregulating ROS levels, and enhance the cytotoxicity of DOX against retinoblastoma.

The Role of Quercetin as a Plant-Derived Bioactive Agent in Preventive Medicine and Treatment in Skin Disorders.

Quercetin, a bioactive plant flavonoid, is an antioxidant, and as such it exhibits numerous beneficial properties including anti-inflammatory, antiallergic, antibacterial and antiviral activity. It occurs naturally in fruit and vegetables such as apples, blueberries, cranberries, lettuce, and is present in plant waste such as onion peel or grape pomace which constitute good sources of quercetin for technological or pharmaceutical purposes. The presented study focuses on the role of quercetin in prevention and treatment of dermatological diseases analyzing its effect at a molecular level, its signal transduction and metabolism. Presented aspects of quercetin potential for skin treatment include protection against aging and UV radiation, stimulation of wound healing, reduction in melanogenesis, and prevention of skin oxidation. The article discusses quercetin sources (plant waste products included), methods of its medical administration, and perspectives for its further use in dermatology and diet therapy.

Docking analysis of phenolic acid and flavonoids with selected TAS2R receptors and in vitro experiment.

Cornelian cherry fruits contain a wide range of phenolic acids, flavonoids, and other secondary metabolites. Selected flavonoids may inhibit the perceiving of bitterness, however, the full mechanism with all TAS2R bitter taste receptors is not known. The aim of the study was to determine the inhibitory effect of Cornus mas phenolics against the bitterness receptors TAS2R13 and TAS2R3 through functional in vitro assays and coupling studies. The overall effect was validated by analysing the inhibition of the receptors activity in cells treated with tested cornelian cherry extracts. The strength of interaction with both TAS2R receptors varied between studied compounds with different binding affinity. Most compounds bonded with the TAS2R3 receptor through a long-distant hydrophobic interaction with Trp89A and π-π orbital overlapping-between phenolic and tryptophane aromatic rings. For TAS2R13 observed were various mechanisms of interaction with the compounds. Nonetheless, naringin and quercetin had most similar binding affinity to chloroquine and denatonium-the model agonists for the receptor.

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 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.

Fast screening of α-glucosidase inhibitors from Ginkgo biloba leaf by using α-glucosidase immobilized on magnetic metal-organic framework.

In this study, a ligand fishing method for the screening of α-glucosidase inhibitors from Ginkgo biloba leaf was established for the first time using α-glucosidase immobilized on the magnetic metal-organic framework. The immobilized α-glucosidase exhibited enhanced resistance to temperature and pH, as well as good thermal stability and reusability. Two ligands, namely quercitrin and quercetin, were screened from Ginkgo biloba leaf and identified by ultra-high performance liquid chromatography-tandem mass spectrometry. The half-maximal inhibitory concentration values for quercitrin and quercetin were determined to be 105.69 ± 0.39 and 83.49 ± 0.79 µM, respectively. Molecular docking further confirmed the strong inhibitory effect of these two ligands. The proposed approach in this study demonstrates exceptional efficiency in the screening of α-glucosidase inhibitors from complex natural medicinal plants, thus exhibiting significant potential for the discovery of antidiabetic compounds.

A chemical analysis of the Pelargonium species: P. odoratissimum, P. graveolens, and P. zonale identifies secondary metabolites with activity against gram-positive bacteria with multidrug-resistance.

The Pelargonium genus encompasses around 280 species, most of which are used for medicinal purposes. While P. graveolens, P. odoratissimum, and P. zonale are known to exhibit antimicrobial activity, there is an evident absence of studies evaluating all three species to understand their chemical differences and biological effects. Through the analysis of the hydroalcoholic extracts of P. graveolens, P. odoratissimum, and P. zonale, using HPLC-DAD-MS/MS, quercetin and kaempferol derivatives were identified in these three species. Conversely, gallotannins and anthocyanins were uniquely detected in P. zonale. P. graveolens stood out due to the various types of myricetin derivatives that were not detected in P. odoratissimum and P. zonale extracts. Evaluation of their biological activities revealed that P. zonale displayed superior antibacterial and antibiofilm activities in comparison to the other two species. The antibacterial efficacy of P. zonale was observed towards the clinically relevant strains of Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus (MRSA) 333, Enterococcus faecalis ATCC 29212, and the Vancomycin-resistant E. faecalis INSPI 032. Fractionation analysis of P. zonale suggested that the antibacterial activity attributed to this plant is due to the presence of quercetin derivatives and kaempferol and its derivatives, alongside their synergistic interaction with gallotannins and anthocyanins. Lastly, the three Pelargonium species exhibited notable antioxidant activity, which may be attributed to their high content of total phenolic compounds.

Quercetin inhibits the epithelial-mesenchymal transition and reverses CDK4/6 inhibitor resistance in breast cancer by regulating circHIAT1/miR-19a-3p/CADM2 axis.

Breast cancer (BC) cells have a high risk of metastasis due to epithelial-mesenchymal transition (EMT). Palbociclib (CDK4/6 inhibitor) is an approved drug for BC treatment. However, the drug resistance and metastasis can impair the treatment outcome of Palbociclib. Understanding the mechanisms of EMT and Palbociclib drug resistance in BC is conducive to the formulation of novel therapeutic strategy. Here, we investigated the role of circHIAT1/miR-19a-3p/CADM2 axis in modulating EMT and Palbociclib resistance in BC. circHIAT1 and CADM2 were down-regulated in BC tissues and cell lines, and miR-19a-3p showed an up-regulation. circHIAT1 could interact with miR-19a-3p and suppress its activity, while miR-19a-3p functioned to negatively regulate CADM2. Forced over-expression of circHIAT1 could impaired the EMT status and migratory ability of BC cells, and this effect was inhibited by miR-19a-3p mimic. In addition, we also generated Palbociclib resistant BC cells, and showed that circHIAT1 and CADM2 were down-regulated in the resistant BC cells while miR-19a-3p showed an up-regulation. Forced circHIAT1 over-expression re-sensitized BC cells to Palbociclib treatment. Quercetin, a bioactive flavonoid, could suppressed the migration and invasion of BC cells, and re-sensitized BC cells to Palbociclib. The anti-cancer effect of quercetin could be attributed to its regulatory effect on circHIAT1/miR-19a-3p/CADM2 axis. In vivo tumorigenesis experiment further revealed that quercetin administration enhanced the anti-cancer effect of Palbociclib, an effect was dependent on the up-regulation of circHIAT1 by quercetin. In summary, this study identified quercetin as a potential anti-cancer compound to reverse Palbociclib resistance and impair EMT in BC cells by targeting circHIAT1/miR-19a-3p/CADM2 axis.

[Quercetin Alleviates H2O2-Induced Oxidative Stress Damage to Human Endometrial Stromal Cells by Inhibiting the p38 MAPK/NOX4 Signaling Pathway]. / æ§²çš®ç´ é€šè¿‡æŠ‘åˆ¶p38 MAPK/NOX4信号通路减轻H2O2è¯±å¯¼çš„äººå­å®«å† è†œåŸºè´¨ç»†èƒžæ°§åŒ–åº”æ¿€æŸä¼¤.

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.

The experimental significance of isorhamnetin as an effective therapeutic option for cancer: A comprehensive analysis.

Isorhamnetin (C16H12O7), a 3'-O-methylated derivative of quercetin from the class of flavonoids, is predominantly present in the leaves and fruits of several plants, many of which have traditionally been employed as remedies due to its diverse therapeutic activities. The objective of this in-depth analysis is to concentrate on Isorhamnetin by addressing its molecular insights as an effective anticancer compound and its synergistic activity with other anticancer drugs. The main contributors to Isorhamnetin's anti-malignant activities at the molecular level have been identified as alterations of a variety of signal transduction processes and transcriptional agents. These include ROS-mediated cell cycle arrest and apoptosis, inhibition of mTOR and P13K pathway, suppression of MEK1, PI3K, NF-κB, and Akt/ERK pathways, and inhibition of Hypoxia Inducible Factor (HIF)-1α expression. A significant number of in vitro and in vivo research studies have confirmed that it destroys cancerous cells by arresting cell cycle at the G2/M phase and S-phase, down-regulating COX-2 protein expression, PI3K, Akt, mTOR, MEK1, ERKs, and PI3K signaling pathways, and up-regulating apoptosis-induced genes (Casp3, Casp9, and Apaf1), Bax, Caspase-3, P53 gene expression and mitochondrial-dependent apoptosis pathway. Its ability to suppress malignant cells, evidence of synergistic effects, and design of drugs based on nanomedicine are also well supported to treat cancer patients effectively. Together, our findings establish a crucial foundation for understanding Isorhamnetin's underlying anti-cancer mechanism in cancer cells and reinforce the case for the requirement to assess more exact molecular signaling pathways relating to specific cancer and in vivo anti-cancer activities.

Controlled Quercetin Release by Fluorescent Mesoporous Nanocarriers for Effective Anti-Adipogenesis.

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis. Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated. Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 µM QUER concentrations, respectively. Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy.

Unravelling effects of phytochemicals from buckwheat on cholesterol metabolism and lipid accumulation in HepG2 cells and its validation through gene expression analysis.

BACKGROUND: The objective of this research was to elucidate the hypocholesterolemic effects of a bioactive compound extracted from buckwheat, and to delineate its influence on the regulatory mechanisms of cholesterol metabolism. The compound under investigation was identified as quercetin. MATERIAL AND RESULTS: In vitro experiments conducted on HepG2 cells treated with quercetin revealed a significant reduction in intracellular cholesterol accumulation. This phenomenon was rigorously quantified by assessing the transcriptional activity of key genes involved in the biosynthesis and metabolism of cholesterol. A statistically significant reduction in the expression of HMG-CoA reductase (HMGCR) was observed, indicating a decrease in endogenous cholesterol synthesis. Conversely, an upregulation in the expression of cholesterol 7 alpha-hydroxylase (CYP7A1) was also observed, suggesting an enhanced catabolism of cholesterol to bile acids. Furthermore, the study explored the combinatory effects of quercetin and simvastatin, a clinically utilized statin, revealing a synergistic action in modulating cholesterol levels at various dosages. CONCLUSIONS: The findings from this research provide a comprehensive insight into the mechanistic pathways through which quercetin, a phytochemical derived from buckwheat, exerts its hypocholesterolemic effects. Additionally, the observed synergistic interaction between quercetin and simvastatin opens up new avenues for the development of combined therapeutic strategies to manage hyperlipidemia.

Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota.

Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Amomum villosum Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR.

From Ethnobotany to Biotechnology: Wound Healing and Anti-Inflammatory Properties of Sedum telephium L. In Vitro Cultures.

Sedum telephium is a succulent plant used in traditional medicine, particularly in Italy, for its efficacy in treating localized inflammation such as burns, warts, and wounds. Fresh leaves or freshly obtained derivatives are directly applied to the injuries for these purposes. However, challenges such as the lack of microbiologically controlled materials and product standardization prompted the exploration of more controlled biotechnological alternatives, utilizing in vitro plant cell cultures of S. telephium. In the present study, we used HPLC-DAD analysis to reveal a characteristic flavonol profile in juices from in vivo leaves and in vitro materials mainly characterized by several kaempferol and quercetin derivatives. The leaf juice exhibited the highest content in total flavonol and kaempferol derivatives, whereas juice from callus grown in medium with hormones and callus suspensions showed elevated levels of quercetin derivatives. The in vitro anti-inflammatory and wound-healing assays evidenced the great potential of callus and suspension cultures in dampening inflammation and fostering wound closure, suggesting quercetin may have a pivotal role in biological activities.

Poly(2-(dimethylamino)ethyl methacrylate)-Grafted Amphiphilic Block Copolymer Micelles Co-Loaded with Quercetin and DNA.

The synergistic effect of drug and gene delivery is expected to significantly improve cancer therapy. However, it is still challenging to design suitable nanocarriers that are able to load simultaneously anticancer drugs and nucleic acids due to their different physico-chemical properties. In the present work, an amphiphilic block copolymer comprising a biocompatible poly(ethylene glycol) (PEG) block and a multi-alkyne-functional biodegradable polycarbonate (PC) block was modified with a number of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) side chains applying the highly efficient azide-alkyne "click" chemistry reaction. The resulting cationic amphiphilic copolymer with block and graft architecture (MPEG-b-(PC-g-PDMAEMA)) self-associated in aqueous media into nanosized micelles which were loaded with the antioxidant, anti-inflammatory, and anticancer drug quercetin. The drug-loaded nanoparticles were further used to form micelleplexes in aqueous media through electrostatic interactions with DNA. The obtained nanoaggregates-empty and drug-loaded micelles as well as the micelleplexes intended for simultaneous DNA and drug codelivery-were physico-chemically characterized. Additionally, initial in vitro evaluations were performed, indicating the potential application of the novel polymer nanocarriers as drug delivery systems.