Narrow Results

The development of nanomaterials using green synthesis methods is gaining attention due to their potential to reduce environmental pollution and health risks associated with traditional chemical synthesis methods. Among the various transition metals, zirconia has gained significant interest as filling materials and implants in dentistry due to its excellent mechanical and chemical properties. In this study, we developed ecofriendly zirconium oxide nanoparticles using Biancaea sappan extract as a capping agent and then functionalized them with Quercetin. Further, their anti-inflammatory property and hemocompatibility were evaluated to target their application as filling materials. The biogenic zirconium oxide nanoparticles (B-ZrO₂NPs) and quercetin functionalized biogenic zirconium oxide nanoparticles (BQZN) were characterized by UV–Vis Spectroscopy (UV–Vis), Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy X-ray analysis (EDX). B-ZrO₂NPs showed maximum absorbance at 267nm and 383nm. FTIR showed characteristic stretching at 3381cm${-1}^{}$, confirming the O–H group in the extract and Quercetin used for BQZN formation. The FTIR spectra of BQZN displayed the presence of the characteristic peaks observed in the spectra of B-ZrO₂NPs and Quercetin. The broad XRD pattern confirmed the amorphous nature of the zirconia. SEM revealed the spherical morphology of B-ZrO₂NPs and BQZN with a size range of around 90nm and 120nm, respectively. EDAX of BQZN revealed the presence of 45.7wt.% Zr, 32.9% oxygen and 21.4% of carbon. In vitro bioactivity studies revealed that BQZN exhibited significant anti-inflammatory activity, as evidenced by the inhibition of protein denaturation. The nanoparticles were also demonstrated for their hemocompatibility with erythrocytes. These findings highlight the potential of BQZN as a promising hemocompatible dental filling with significant anti-inflammatory properties. Further in-depth in vivo studies are required to fully understand their efficacy and toxicity.

The oxidative damage initiated by reactive oxygen species (ROS) is a major contributor to the functional decline and disability that characterizes aging. The anti-oxidant flavonoid, quercetin, is a plant polyphenol that may be beneficial for retarding the aging process. We examined the restoring properties of quercetin on human dermal fibroblasts (HDFs). Quercetin directly reduced either intracellular or extracellular ROS levels in aged HDFs. To find the aging-related target genes by quercetin, microarray analysis was performed and two up-regulated genes LPL and KCNE2 were identified. Silencing LPL increased the expression levels of senescence proteins such as p16^INK4A and p53 and silencing KCNE2 reversed gene expressions of EGR1 and p-ERK in quercetin-treated aged HDFs. Silencing of LPL and KCNE2 decreased the expression levels of anti-oxidant enzymes such as superoxide dismutase and catalase. Also, the mitochondrial dysfunction in aged HDFs was ameliorated by quercetin treatment. Taken together, these results suggest that quercetin has restoring effect on the cellular senescence by down-regulation of senescence activities and up-regulation of the gene expressions of anti-oxidant enzymes in aged HDFs.

Yang-Yin-Qing-Fei-Tang (YYQFT) is a well-known traditional Chinese medicine used in the treatment of chronic obstructive pulmonary emphysema, bronchitis, cytomegaloviral pneumonia, but the mechanisms of the medicine are not clear. This study aimed to identify the active components of YYQFT and elucidate the underlying mechanism on non-small cell lung cancer. First, YYQFT was extracted with different solvents, and then the most effective extract was determined by assessing their effects on non-small cell lung cancer cell growth. Second, several active compounds from YYQFT were identified, and quercetin was the one of the important active ingredients. Subsequently, the in vivo antitumor activity of quercetin was confirmed in a lung cancer xenograft model in mice. 200$\mu$g/mL quercetin significantly reduced tumor volume without affecting body weight of the mice. Furthermore, induction of apoptosis by quercetin was detected in tumor tissues treated with quercetin. Multiple apoptosis related genes including p53, Bax and Fas were upregulated by quercetin in tumor tissue and the ratio of Bax/Bcl-2 was increased accordingly. Our results demonstrated that quercetin, as the main effective component of the YYQFT, has potent inhibitory activity on non-small cell lung cancer by regulating the ratio of Bax/Bcl-2.

Gliomas are the mostly observed form of primary brain tumor, and glioblastoma multiforme (GBM) shows the highest incidence. The survival rate of GBM is fairly poor; thus, discovery of effective treatment options is required. Among several suggested targets for therapy, the Axl/IL-6/STAT3 signaling pathway has gained recent interest because of its important role within cancer microenvironment. Quercetin, a plant flavonoid, is well known for its anticancer action. However, the effect of quercetin on Axl has never been reported. Quercetin treatment significantly reduced cell viability in two GBM cell lines of U87MG and U373MG while keeping 85% of normal astrocytes alive. Further western blot assays suggested that quercetin induces apoptosis but does not affect Akt or mitogen-activated protein kinases, factors related to cell proliferation. Quercetin also decreased IL-6 release and phosphorylation of STAT3 in GBM cells. In addition, gene expression, protein expression, and half-life of synthesized Axl protein were all suppressed by quercetin. By applying shRNA for knockdown of Axl, we could confirm that the role of Axl was crucial in the apoptotic effect of quercetin on GBM cells. In conclusion, we suggest quercetin as a potential anticancer agent, which may improve cancer microenvironment of GBM via the Axl/IL-6/STAT3 pathway.

Cisplatin is massively used to treat solid tumors. However, several severe adverse effects, such as cardiotoxicity, are obstacles to its clinical application. Cardiotoxicity may lead to congestive heart failure and even sudden cardiac death in patients receiving cisplatin. Therefore, finding a novel therapeutic strategy for the prevention of cisplatin-induced cardiotoxicity is urgent. Quercetin is a flavonol compound that can be found in dietary fruits and vegetables. The antioxidant function and anti-inflammatory capacity of quercetin have been reported. However, whether quercetin could protect against cisplatin-caused apoptosis and cellular damage in cardiomyocytes is still unclear. H9c2 cardiomyocytes were treated with cisplatin (40 μM) for 24 h to induce cellular damage with or without quercetin pretreatment. We found that quercetin activates Nrf2 and HO-1 expression, thereby mitigating cisplatin-caused cytotoxicity in H9c2 cells. Quercetin also increases SOD levels, maintains mitochondrial function, and reduces oxidative stress under cisplatin stimulation. Quercetin attenuates cisplatin-induced apoptosis and inflammation in H9c2 cardiomyocytes; however, these cytoprotective effects were diminished by silencing Nrf2 and HO-1. In conclusion, this study reports that quercetin has the potential to antagonize cisplatin-caused cardiotoxicity by reducing ROS-mediated mitochondrial damage and inflammation via the Nrf2/HO-1 and p38MAPK/NF-$\kappa$Bp65/IL-8 signaling pathway. This study provided the theoretical basis and experimental proof for the clinical application of quercetin as a new effective strategy to relieve chemotherapy-induced cardiotoxicity.

The variable dosage forms of most traditional Chinese medicines (TCMs) could be disadvantaged by low selectivity, poor biological distribution, limited bioavailability with low efficacy, and some adverse effects. These issues limit the control of clinical pharmacodynamics of the antitumor active components. With the progress of science and technology, many new polymer materials and new technologies have emerged, such as nanotechnology, cyclodextrin inclusion, solid dispersion, microcapsule and microsphere technologies. These new technologies provide a good basis for exploring novel TCM dosage forms for overcoming the shortcomings. The increased numbers of new technologies have been used to study TCM dosage forms with remarkable achievements. In this review paper, we will provide a systematic overview of the new dosage forms of nano-formulations and co-medications in relation to nano-delivery systems in an attempt to provide useful references for practical application of active antitumor ingredients from the TCMs.

Intrahepatic cholangiocarcinoma (ICC) is a rare, highly fatal hepatobiliary malignancy, with very limited treatment options and, consequently, a poor prognosis. Recently, emerging evidence has suggested the potential of quercetin (QE) for use in cancer therapy. The purpose of this study is to investigate whether QE could inhibit ICC. The effects of QE on the proliferation, apoptosis, and invasion of ICC were analyzed in vitro. The inhibitory effect of QE on ICC was also verified in vivo. The RNA sequence was applied to explore the mechanism of QE. Functional verification was also performed after RNA sequencing using activators and inhibitors of nuclear factor-kappa-B (NF-$\kappa$B) and ferroptosis. The results showed that QE could inhibit the proliferation and survival of ICC cells, induce the arrest of ICC cells in the G1 phase, promote the apoptosis of ICC cells, and inhibit the invasion of ICC cells. Furthermore, QE could promote ferroptosis in ICC cells by inhibiting the NF-$\kappa$B pathway. In conclusion, QE is a new ferroptosis inducer and NF-$\kappa$B inhibitor that can not only induce ferroptosis, but also inhibit the invasion of ICC cells, providing a prospective strategy for the treatment of ICC.

The imbalance of bone homeostasis has become a major public medical problem amid the background of an aging population, which is closely related to the occurrence of osteoporosis, osteoarthritis, and fractures. Presently, most drugs used in the clinical treatment of bone homeostasis imbalance are bisphosphonates, calcitonin, estrogen receptor modulators, and biological agents that inhibit bone resorption or parathyroid hormone analogs that promote bone formation. However, there are many adverse reactions. Therefore, it is necessary to explore potential drugs. Quercetin, as a flavonol compound with various biological activities, is widely distributed in plants. Studies have found that quercetin can regulate bone homeostasis through multiple pathways and targets. An in-depth exploration of the pharmacological mechanism of quercetin is of great significance for the development of new drugs. This review discusses the therapeutic mechanisms of quercetin on bone homeostasis, such as regulating the expression of long non-coding RNA, signaling pathways of bone metabolism, various types of programmed cell death, bone nutrients supply pathways, anti-oxidative stress, anti-inflammation, and activation of Sirtuins. We also summarize recent progress in improving quercetin bioavailability and propose some issues worth paying attention to, which may help guide future research efforts.

Quercetin (3,3${}^{\prime }$,4${}^{\prime }$,5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8${}^{+}$ T lymphocytes, and CD4${}^{+}$ T lymphocytes and promoting the secretion of IL-2 and IFN-$\gamma$ from CD8${}^{+}$ T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8${}^{+}$ T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8${}^{+}$ T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH₂-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective $\mathrm{\text{factor}}>2$). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

A nonlinear modeling of the protective effect of Quercetin (QCT) against various Mycotoxins (MTXs) has a high complexity and is conducted using artificial neural networks (ANNs). QCT is known to possess strong anti-oxidant, anti-inflammatory activity that can prevent many diseases. MTXs are highly toxic secondary metabolites that are capable of causing disease and death in humans and animals. The protective model of QCT against various MTXs (Citrinin, Patulin and Zearalenol) on HeLa cell is built accurately via learning of sparsely measured experimental data by the ANNs. It has shown that the neuro-model can predict the nonlinear protective effect of QCT against MTX-induced cytotoxicity for the measurement of percentage of inhibition of MTXs.

Over the years, the (multi)fractal nature of signals describing the activity of ion channels has been observed both at the level of single-channel currents and the temporal scaling of the corresponding sojourns in conducting and non-conducting states. The recognized nonlinear and self-similar properties were interpreted regarding the underlying channel gating machinery. Nevertheless, the literature lacks in (multi)fractal description of the biochemical stimulation of ion channels. Therefore, in this work, we provide a multifractal description of the effects exerted by two different flavonoids — naringenin (Nar) and quercetin (Que) — being the regulators of the large-conductance voltage- and Ca${}^{2+}$-activated K${}^{+}$ channels from the inner mitochondrial membrane (mitoBK). Toward this aim, the focus-based multifractal detrended fluctuation analysis (MFDFA) was applied to the patch-clamp data obtained in the presence of Nar and Que in micromolar concentrations and the corresponding controls. Our results show that mitoBK channel activity has well-pronounced multifractal characteristics and long-range memory (measured by the generalized Hurst exponent) under biochemical stimulation by Nar and Que and in the absence of these substances. The spectral properties significantly change after the randomization of the analyzed series. Therefore, multifractality is an inherent feature of the mitoBK channel currents, which stems from their statistical distribution and temporal organization. Both flavonoids have similar structures and exert channel-activating effects, but they differently affect the parameters of the multifractal spectra of the corresponding patch-clamp signals. Coordination of Que leads to more prominent changes in signal complexity than Nar at membrane hyper- and depolarization. It suggests that this flavonoid has a stronger impact on the conformational dynamics of the mitoBK channels in comparison with naringenin.

Quercetin is a naturally occurring cytotoxic compound where clinical use has been limited by its low water solubility. Therefore, liposomes were explored for solubilizing quercetin. Liposomes composed of DPPC (1,2 dipalmitoyl-sn-glycerol-3-phosphocholine)/DSPE-PEG₂₀₀₀ (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)₂₀₀₀])/quercetin (90:5:5 mole ratio) incorporated quercetin efficiently at 100.9 ± 4.6% and increased quercetin concentration in water 11.2-fold. Stability studies at storage temperature of 4°C showed that the liposomes were stable for up to 16 weeks, without any significant changes in diameters. Liposomal quercetin showed a delayed release profile and reduced quercetin degradation. In vitro cytotoxicity tests also showed that the ED₅₀ of liposomal quercetin was 17.6 times lower than free quercetin in MDA-MB-231 breast cancer cells. In conclusion, the DPPC/DSPE-PEG-based liposomes were stable and were capable of solubilizing quercetin, preventing quercetin degradation, and increasing quercetin in vitro cytotoxicity. Hence, liposomes are a suitable nanocarrier for quercetin.

Momordica charantia, known as “São Caetano Melon”, is a medicinal plant popularly used for its antitumor, anticarcinogenic, hypoglycemic, and other properties. Studies in mice have demonstrated its activity in vivo against breast, prostate, and ovarian cancers. In vitro studies have also indicated potential efficacy against cervical solid tumors, and breast cancer. In these studies, we sought to evaluate these putative activities. Our methods included use of in silico tools to assess predicted biological activities, pharmacodynamics, and toxicity. We also performed docking and pharmacophore modeling studies. We found phenolic compounds, flavonoids, alkaloids, and triterpenes. Four flavonoids possess predicted anticarcinogenic activity, and affinity for estrogen receptors. Quercetin was selected for the study because it is the most prevalent representative of its class.

The biodegradability of inorganic nanocarriers is one of the most critical issues in their further clinical translations. In this work, a manganese-doped approach was developed to endow inorganic mesoporous silica (SiO₂) nanospheres with pH-sensitive biodegradation. Manganese-doped mesoporous silica nanospheres (MMS) were prepared by in-situ doping method, with a particle diameter of 160–175 nm and pore diameter of 3–5nm by characterization of N₂ adsorption method, powder X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectrum, field emission scanning electron microscope and transmission electron microscope techniques. Quercetin was used as the model drug to load, and MMS loaded with quercetin (MMS–QUE) was surface-modified using a carboxymethyl chitosan (MMS–QUE–CMCS) to prevent quercetin leakage. Based on the dissolution characteristics of manganese ions and the swelling behavior of carboxymethyl chitosan, the MMS–QUE–CMCS could be degraded in response to acid. The MMS–QUE–CMCS delivery system exhibited a good pH-responsive release. The cytotoxicity test showed that the MMS–QUE–CMCS had a significant biocompatibility and an enhanced cytotoxicity, thus revealing that the MMS–QUE–CMCS was a promising delivery system.

Silver nanoparticles (AgNPs) occupy a major part in biomedicine due to their unique physicochemical and biological properties including anti-microbial and anti-cancer activity. Evolvulus alsinoides (EA), commonly known as “Dwarf morning glory”, is a flowering plant with unique medicinal properties. This plant is reported for its therapeutic significance in chronic bronchitis, asthma and even possesses higher pharmacological properties. In this study, we have reported the synthesis and biological properties of quercetin functionalized biogenic silver nanoparticles (Qur-EA-AgNPs). AgNPs were synthesized using EA Leaf extract and functionalized with Quercetin. Qur-EA-AgNPs were characterized using various techniques and their biocompatibility was investigated. The UV-Visible spectrum of EA-AgNPs revealed a maximum absorbance at 428nm and quercetin functionalization results in a shift towards 390nm. The intense peak in the Fourier-transform infrared spectroscopy (FTIR) spectra revealed the quercetin functionalization on EA-AgNPs. Scanning electron microscope (SEM) results confirmed the spherical morphology of quercetin-functionalized AgNPs with a size range around 20nm which was further confirmed by High resolution transmission electron microscope (HRTEM). Energy Dispersive X-ray (EDX) spectrum evidenced the presence of Ag, C and O. Hemocompatibility of Qur-EA-AgNPs was confirmed from hemolytic assay showing $<$5% hemolysis. Moreover, Annexin V PI assay on Qur-EA-AgNPs treated peripheral blood mononuclear cells (PBMCs) showed 78.58 % viability significantly which is comparable with the control cells and its biocompatible nature was proved.

Despite the emergence of numerous carbon dots (CDs)-based sensors, most of them are fluorescent probes. To improve the reliability of the results, using ratiometric fluorescence/UV-vis absorption dual-signal probes is an effective method. Herein, nitrogen and chlorine co-doped carbon dots (N, Cl-CDs) with yellow-green fluorescence were prepared and used as a dual-function probe for ratiometric fluorescence/UV-vis. The detection range of the fluorescence method was 0.05–78$\mu$M, and the limit of detection (LOD) was 1.2nM (3$\sigma$/s). For the colorimetric method, the linear range was 0.05–186$\mu$M with LOD of 10.7nM. Importantly, the N, Cl-CDs were successfully used to detect Quercetin (QT) in actual water samples. Besides, due to their good biocompatibility, the N, Cl-CDs were applied to in vivo biological imaging of oocysts and shown the potential for environmental survey and biological assay.

Objectives: In this study, we assess the possible influence of soybean isoflavone (genistein) and other flavonoids (quercetin and catechin) on breast cancer chemoprevention. We design in-vitro and in-vivo experiments to analyze the effect of genistein, quercetin and catechin on cell proliferation, cell migration, and angiogenesis of breast cancer cells.

Methods: In cell proliferation experiment, MCF-7 cells, SKBR-3 cells, and HUVEC cells were treated with genistein and other flavonoids (catechin and/or quercetin) for 48h to assess the influence on cell growth of normal and breast cancer cells. In cell motility test, we analyze the effect of isoflavone and flavonoids on migration ability of MCF-7 cells by 16h and SKBR-3 cells by 24h in two different concentrations (1.25$\mu$g/ml and 2.5$\mu$g/ml). In the in-vivo experiment, SKBR-3 cells mixed with PBS and catechin, respectively, were injected subcutaneously into nude mice, then we investigated the effect of catechin on cell growth by observing subcutaneous tumor size changes after 15 days.

Results: The results suggest that genistein and quercetin can significantly inhibit proliferation of breast cancer cells, and their inhibitory effects are independent of estrogen receptor. In cell motility tests, all of the three phytochemicals were effective in the inhibition of cell migration on two breast cancer cell lines, except for quercetin on cell migration of SKBR-3 cell line. In the in-vitro experiment, catechin showed stimulatory effect on cell proliferation of HUVEC cell line, which may consider positive effect on angiogenesis, rather than inhibitory effect. However, in the in-vivo experiment, it showed no significant change in tumor size between the groups of with and without catechin treatment.

Conclusions: According to our study, the results suggest that isoflavone and flavonoids tend to inhibit cell growth and metastasis of breast cancer cells. Our in-vivo experiment does not reach a significant result, and it may be due to lower catechin concentration. Under in-vivo environment, we should also consider the possible metabolic forms of catechin that cause different result from the in-vitro study.