Network pharmacology and molecular docking analysis based on mechanism of Huangqin Tang in treatment of colorectal cancer / 吉林大学学报(医学版)

Objective:To analyze the potential therapeutic targets of Huangqin Tang in treatment of colorectal cancer(CRC)by network pharmacology and molecular docking techniques,and to clarify the related molecular mechanism.Methods:The active component and target dataset for Huangqin Tang were constructed based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);the CRC-disease related target dataset was built by Databases such as GeneCards,Online Mendelian Inheritance in Man(OMIM),and pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB).Drug-disease target intersect,Huangqin Tang herbal formula network,and protein-protein interaction(PPI)networks were built by R software,Cytoscape software,and STRING Database;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted by R software and Metascape platform;molecular docking validation was performed with AutoDock and PyMOL software to assess the ligand-receptor binding.Results:A total of 136 effective active components of Huangqin Tang were screened,and 242 potential targets were identified for treatment of CRC,including 18 core targets.Five core key targets closely related to CRC,identified through signaling pathway analysis,were protein kinase B1(AKT1),mitogen-activated protein kinase 3(MAPK3),proto-oncogene FOS,tumor protein p53(TP53),and proto-oncogene MYC.The GO functional enrichment analysis results mainly involved various biological processes related to cellular stress responses.The KEGG signaling pathway enrichment analysis results showed that potential targets were highly enriched in the cancer pathway;further analysis on CRC core targets via KEGG signaling pathway revealed involvement primarily in pathways related to endocrine resistance,apoptosis,and epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)resistance.The molecular docking results showed that the active components of Huangqin Tang,including quercetin,kaempferol,baicalein,7-methoxy-2-methyl isoflavone,and naringenin,were stably docked with AKT1,MAPK3,FOS,TP53,and MYC,and quercetin exhibited the best binding with AKT1.Conclusion:The active components of Huangqin Tang can treat CRC through multi-target and multi-pathway.The core ligand quercetin and AKT1 may exert the therapeutic effect in CRC by regulating the phosphatidylinositol 3-kinase(PI3K)/AKT and mammalian target of rapamycin(mTOR)signaling pathways to influence the cell proliferation,differentiation,and apoptosis processes.

Mechanism of quercetin alleviating postherpetic neuralgia in rats by inhibiting MIP-1α/CCR1/CCR5 signaling pathway / 天津医药

Objective To investigate the impact of quercetin(Que)on postherpetic neuralgia(PHN)and chemokine ligand 3(CCL3,namely MIP-1α)/C-C chemokine receptor 1(CCR1)/C-C chemokine receptor 5(CCR5)signaling pathway in rats.Methods Sixty rats were divided into the control group(Con),the PHN group(model group),the L-Que(30 mg/kg)group,the M-Que(60 mg/kg)group,the H-Que(120 mg/kg)group and the H-Que+pathway activator MIP-1α(120 mg/kg Que+0.4 mg/kg recombinant MIP-1α)group.The mechanical paw withdrawal threshold(PWT)and thermal pain threshold(TWL)of rats were detected in each group.The kit was used to detect adenosine,Adenine ribonucleotide(AMP),adenosine diphosphate(ADP)and tumor necrosis factor in spinal dorsal horn samples-α(TNF-α),and interleukin-1 β(IL-1 β)levels in spinal dorsal horn samples.HE staining was applied to observe the pathological sections of spinal dorsal horn.Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn.Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression.Results In the PHN group,the dorsal horn of the spinal cord was ruptured,the arrangement of nerve bundles was disordered,and inflammatory cell infiltration,edema,and slight atrophy of neurons appeared.Compared with the Con group,the PWT value,adenosine,AMP and ADP levels were obviously decreased in the PHN group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1-positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).After treatment with Que,the disordered arrangement of nerve bundles was improved,the infiltration of inflammatory cells was reduced,and the phenomenon of neuronal atrophy disappeared.Compared with the PHN group,the PWT value,adenosine,AMP and ADP levels were obviously increased in the L-Que group,the M-Que group and the H-Que group(P＜0.05).TWL value,TNF-αand IL-1β levels,the number of Iba1-positive microglia,and MIP-1α,CCR1 and CCR5 protein levels were obviously decreased(P＜0.05).The effect of Que was dose dependent.Compared with the H-Que group,PWT value,adenosine,AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1 positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway,thereby reducing PHN.

Quercetin targets CCR1 and CXCR4 to promote migration of human bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells,but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE:To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments,and to explore the regulatory role of CCR1 and CXCR4. METHODS:Human bone marrow mesenchymal stem cells were selected as experimental subjects.CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells.Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment,respectively.The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology.Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION:(1)5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells,and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency.(2)To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells,5 and 10 μmol/L quercetin were selected for the subsequent experiments,and ligustrazine was used as the positive control drug,and the experiments were divided into blank control group,5 μmol/L quercetin group,10 μmol/L quercetin group,and 100 μmol/L ligustrazine group.(3)In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment,and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group.(4)The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4.(5)Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA.(6)This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4.

Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome / 中国药房

OBJECTIVE To investigate the protective effect and mechanism of quercetin on the cardiac and renal functions of rats with cardiorenal syndrome （CRS） based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa- B （NF-κB） signaling pathway. METHODS CRS model of SD rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion. Model rats were randomly separated into model group， quercetin low-dose group （35 mg/kg）， quercetin high-dose group （70 mg/kg）， high-dose of quercetin+740Y-P group （70 mg/kg quercetin+3.5 mg/kg PI3K/Akt/ NF-κB signaling pathway activator 740Y-P）， with 12 rats in each group. Another 12 normal rats were selected as sham operation group. They were given relevant drugs， once a day， for 14 consecutive days. After administration， the cardiac function indexes [left ventricular ejection fraction （LVEF）， end-diastolic volume （EDV）， isovolumic relaxation time （IVRT）] and renal function indicators [blood urea nitrogen （BUN）， 24-hour urine protein， and serum creatinine （Scr）] were detected， and fibrosis in the cardiac and renal tissues was observed； the levels of inflammatory indexes [interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）] in the serum and cardiac and renal tissues as well as the expression of PI3K/Akt/NF-κB pathway-related proteins in the cardiac and renal tissues were detected. RESULTS Compared with sham operation group， the levels of BUN， 24-hour urine protein and Scr， collagen volume fraction of cardiac and renal tissues， the levels of IL-1β and TNF-α in serum and cardiac and renal tissues， and the phosphorylation of PI3K， Akt and NF-κB p65 protein in cardiac and renal tissues were increased significantly in model group （P＜0.05）； the levels of LVEF， IVRT and EDV were reduced significantly （P＜0.05）. Compared with the model group， the above indexes were reversed significantly in quercetin low-dose and high-dose groups （P＜0.05）， and the reversal effect was better in the high-dose group （P＜0.05）. 740Y-P restored the reverse effect of high-dose quercetin on the indexes （P＜0.05）. CONCLUSIONS Quercetin can alleviate cardiac and renal fibrosis and function injury， the mechanism of which may be 20232016） associated with inhibiting the activation of the PI3K/Akt/NF-κB signaling pathway.

Mechanism of Active Ingredients of Astragalus Membranacus in Treating Heart Failure： A Review / 中国实验方剂学杂志

Heart failure is one of the main cardiovascular system diseases at present， and it is a clinical syndrome caused by changes in cardiac structure and function， resulting in impaired ejection function or ventricular filling. Therefore， heart failure has become the most important cardiovascular disease in the 21st century. In recent years， the incidence of heart failure is increasing， and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine， more and more attention has been paid to the research， development， and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus， a traditional Chinese medicine， is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics， protecting myocardial muscle， and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure， yielding remarkable results. In recent years， it has been found that astragaloside， Astragalus polysaccharide， quercetin， calyx isoflavones， and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response， myocardial apoptosis， and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature， with a view to providing a reference for its further research， development， and application in the prevention and treatment of heart failure.

Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity / 中国药理学通报

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Quercetin plays a neuroprotective role in inhibiting mitochondrial apoptosis by mediating JNK signaling pathway / 中国药理学通报

Aim To study the mechanism of quereetin (Que) inhibiting mitochondrial damage induced by Aβ

Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

Effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia / 中国药房

OBJECTIVE To investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia. METHODS H9c2 cells were divided into blank group， model group， quercetin high-dose， medium-dose and low-dose groups （40， 20， 10 μmol/L）， and positive control group （cyclosporine A， 1 μmol/L）. Reactive oxygen species （ROS）， mitochondrial membrane potential （MMP）， openness of mitochondrial permeability transition pore （MPTP）， adenosine triphosphate （ATP）， malondialdehyde （MDA）， lactate dehydrogenase （LDH） and creatine kinase （CK） were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group， model group， quercetin high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg）， and positive control group （trimetazidine， 6.3 mg/kg）， with 8 rats in each group. They were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last medication， myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH， MDA， creatine kinase isoenzyme-MB （CK-MB）， superoxide dismutase （SOD）， complex Ⅰ， complex Ⅳ and ATP in serum were all determined. RESULTS Compared with the model group， ROS fluorescence intensity， openness of MPTP， the contents of CK， LDH and MDA were significantly decreased in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of MMP and ATP were all increased significantly （P＜0.01）； the contents of CK-MB， LDH and MDA in serum were all decreased significantly in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of SOD， complex Ⅰ， complex Ⅳ and ATP （except for positive control group） were increased significantly （P＜ 0.05 or P＜0.01）. CONCLUSIONS Quercetin can effectively reduce myocardial hypoxic injury， promote endogenous energy production and improve mitochondrial function after myocardial ischemia.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Study on the potential molecular mechanism of Ziyabiti tablets on type 2 diabetes based on network pharmacology / 中国药师

Objective To study the molecular mechanism of Ziyabiti tablets in the treatment of type 2 diabetes(T2DM)by network pharmacology.Methods The chemical components and related targets of Ziyabiti tablets were obtained from TCMSP,ETCM and CNKI,and the targets of T2DM were screened by OMIM and GeneCards databases.The"drug-component-target"network was built by Cytoscape 3.6.1 to screen out the core components and the core targets were screened by protein-protein interaction network.GO functional analysis and KEGG pathway enrichment analysis were performed by DAVID database.Results A total of 144 active components of Ziyabiti tablets were collected in this study,and quercetin,kaempferol,isorhamnetin and so on with higher degree values.There were 823 related targets,of which 700 were related to T2DM,including SRC,MAPK1,MAPK3,etc.GO function analysis suggested that it was related to molecular functions such as signal transduction,protein phosphorylation and protein binding.The main signaling pathways involved in KEGG pathway enrichment analysis were AGE-RAGE signaling pathways in lipid and atherosclerosis,prostate cancer,and diabetic complications.Conclusion Ziyabiti tablets have the characteristics of multi-component,multi-target,and multi-pathway synergistic intervention in the treatment of T2DM,which is mainly composed of quercetin,kaempferol,isorhamnetin and other components to regulate AGE-RAGE signaling pathways through SRC,MAPK1,MAPK3 targets.

Folic Acid-Modified Liposome Quercetin Induces Apoptosis of Triple-Negative Breast Cancer Cells via Mitochondrial Apoptosis Mediated by JAK2/STAT3 Signaling Pathway / 肿瘤防治研究

Objective To investigate the effect of folic acid–modified liposome quercetin (FLQ) on the proliferation and apoptosis of triple negative breast cancer (TNBC) cells and explore its underlying mechanism. Methods CCK-8 was used to detect the effect of FLQ on TNBC cell viability. Colony formation assay was conducted to detect the effect of FLQ on TNBC cell proliferation. Flow cytometry was performed to detect the effect of FLQ on TNBC cell apoptosis, the levels of intracellular ROS, and mitochondrial membrane potential. Western blot analysis was conducted to detect the expression levels of JAK2/STAT3 signaling pathway-related and apoptosis-related proteins. Results FLQ inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells (P=0.023, P<0.001). It promoted mitochondrial membrane potential collapse and increased the intracellular ROS levels of MDA-MB-231 cells (P=0.003, P=0.034); inhibited the phosphorylation levels of JAK2 and STAT3; upregulated the expression levels of the proapoptotic proteins Bax, Bak, cytochrome C, and Cleaved-Caspase-3 (P<0.001, P<0.001); and downregulated the expression levels of the antiapoptotic proteins Bcl2 and Bcl-xL (P=0.037, 0.028). Conclusion FLQ inhibits the proliferation and induces the apoptosis of MDA-MB-231 cells. These effects may be related to the activation of the mitochondrial apoptosis pathway through the inhibition of the JAK2/STAT3 signaling pathway.

Comparación potencial de las actividades antiinflamatorias de las formulaciones de enjuague bucal de quercetina y diclofenaco / Potential Comparison of Anti-inflammatory Activities of Quercetin and Diclofenac Mouthwash Formulations

Introduction: Periodontitis is a pandemic, with about 14 percent of people worldwide already suffering from severe periodontitis. Early intervention in the disease could probably reduce its progression and eliminate the need for the extraction of affected teeth. Quercetin is a probable candidate as it has exemplary anti-inflammatory properties. The presence of phenolic hydroxyl groups in them greatly contributes to their antioxidant and anti-inflammatory activities. Objectives: The study introduces the formulation of Quercetin mouthwash and assesses its anti-inflammatory properties in comparison to Diclofenac sodium. Methods: Quercetin mouthwash was prepared using a commercially procured bioactive agent. One standard nonsteroidal anti-inflammatory drug, Diclofenac was used as a reference drug. The percentage inhibition of protein denaturation was calculated and its anti-inflammatory properties were evaluated through Bovine Serum Albumin Assay and Egg Albumin Assay. Results: Quercetin mouthwash showed parallel anti-inflammatory properties and showed a proportionate increase in anti-inflammatory properties with the increase in the concentration of the mouthwash. Comparable inhibition of protein denaturation at 10µl and 50µl concentrations with a proportionate variation of 1 percent (p>0.05) to the control in Egg Albumin Assay and 47 percent and 83 percent denaturation at 10µl and 50µl of Bovine Serum Albumin Assay were observed. Conclusion: Quercetin mouthwash has shown significant anti-inflammatory activity and hence is considered a potent anti-inflammatory agent comparable to Diclofenac sodium. It is found to be a suitable agent as an oral formulation for reducing the progression of inflammatory conditions(AU)

Introducción: La periodontitis es una pandemia, ya que alrededor del 14 por ciento de las personas en todo el mundo padecen periodontitis grave. Una intervención precoz en la enfermedad podría, probablemente, reducir su progresión y eliminar la necesidad de extraer los dientes afectados. La quercetina es un candidato probable, ya que tiene propiedades antiinflamatorias ejemplares. Su presencia de grupos hidroxilos fenólicos contribuye en gran medida a sus actividades antioxidantes y antiinflamatorias. Objetivos: El estudio presenta la formulación del colutorio de quercetina y evalúa sus propiedades antiinflamatorias en comparación con el diclofenaco sódico. Métodos: Se preparó un colutorio de quercetina, utilizando un agente bioactivo obtenido comercialmente. Se utilizó como fármaco de referencia un antiinflamatorio no esteroideo estándar, el diclofenaco. Se calculó el porcentaje de inhibición de la desnaturalización de proteínas y se evaluaron sus propiedades antiinflamatorias mediante ensayo con albúmina de suero bovino y con albúmina de huevo. Resultados: El colutorio de quercetina mostró propiedades antiinflamatorias paralelas y mostró un aumento proporcional de las propiedades antiinflamatorias con el aumento de la concentración del colutorio. Se observó una inhibición comparable de la desnaturalización de proteínas a concentraciones de 10µl y 50µl con una variación proporcional del 1 por ciento (p > 0,05), respecto al control en el ensayo de albúmina de huevo y una desnaturalización del 47 por ciento y 83 por ciento a 10µl y 50µl del ensayo de albúmina de suero bovino. Conclusiones: El enjuague bucal de quercetina ha mostrado una actividad antiinflamatoria significativa, por lo que se considera un potente agente antiinflamatorio comparable al diclofenaco sódico. Se considera un agente adecuado como formulación oral para reducir la progresión de las afecciones inflamatorias(AU)

Valorization of Campomanesia xanthocarpa leaves: chemical composition and antioxidant activity of crude extract and fractions / Valorización de hojas de Campomanesia xanthocarpa: composición química y actividad antioxidante de extracto crudo y fracciones

Campomanesia xanthocarpa leaves are a byproduct of fruit production without studies on antioxidant activity. Thus, this study aimed to identify the antioxidant compounds of C. xanthocarpaleaves by ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-ESI/qTOF) and by different in vitro antioxidant methods. The crude extract of C. xanthocarpa leaves had a yield of 15.2% and only five out of 37 fractions of the crude extract had antioxidant activity. The crude extract presented greater antioxidant activity than the isolated fractions. The identified antioxidant compounds were phenolic acids (gallic acid and chlorogenic acid), flavonoids (quercetin and naringenin 7,4'-dimethoxy) and an organic acid (quinic acid). Leaves of C. xanthocarpa have high concentration of antioxidant compounds and it is a promising plant for the development of applications in the food, cosmetic, and pharmaceutical fields. The extraction of antioxidant compounds can add value to the productive chain of this plant.

Las hojas de Campomanesia xanthocarpa son un subproducto de la producción de frutos sin estudios sobre la actividad antioxidante. Así, este estudio tuvo como objetivo identificar los compuestos antioxidantes de las hojas de C. xanthocarpa mediante cromatografía líquida de ultra alta resolución acoplada con espectrometría de ionización-cuadrupolo-tiempo de vuelo-masa por electropulverización (UHPLC-ESI / qTOF) y mediante diferentes métodos antioxidantes in vitro. El extracto crudo de hojas de C. xanthocarpa tuvo un rendimiento del 15,2% y solo cinco de las 37 fracciones del extracto crudo tuvieron actividad antioxidante. El extracto crudo presentó mayor actividad antioxidante que las fracciones aisladas. Los compuestos antioxidantes identificados fueron ácidos fenólicos (ácido gálico y ácido clorogénico), flavonoides (quercetina y naringenina 7,4'-dimetoxi) y un ácido orgánico (ácido quínico). Las hojas de C. xanthocarpa tienen una alta concentración de compuestos antioxidantes y es una planta prometedora para el desarrollo de aplicaciones en los campos alimentario, cosmético y farmacéutico. La extracción de compuestos antioxidantes puede agregar valor a la cadena productiva de esta planta.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Bioinformatics analysis and validation of key genes in transformation of idiopathic membranous nephropathy to end-stage renal disease and traditional Chinese medicines for prevention and treatment / 中国中药杂志

This study used bioinformatics analysis to screen out key genes involved in the transformation of idiopathic membranous nephropathy to end-stage renal disease and to predict targeted Chinese herbs and medicines and active ingredients with preventive and curative effects. The GSE108113 microarray of idiopathic membranous nephropathy and GSE37171 microarray of were downloaded from the comprehensive gene expression database, and 8 homozygous differentially expressed genes for the transformation of idiopathic membranous nephropathy into end-stage renal disease of were screened out by R software. GraphPad Prism was used to verify the expression of homozygous differentially expressed genes in GSE115857 microarray of idiopathic membranous nephropathy and GSE66494 microarray of chronic kidney disease, and 7 key genes(FOS, OGT, CLK1, TIA1, TTC14, CHORDC1, and ANKRD36B) were finally obtained. The Gene Ontology(GO) analysis was performed. There were 209 functions of encoded proteins, mainly involved in regulation of RNA splicing, cytoplasmic stress granule, poly(A) binding, etc. Thirteen traditional Chinese medicines with the effect of preventing the transformation of idiopathic membranous nephropathy to end-stage renal disease were screened out from Coremine Medical database, including Ginseng Radix et Rhizoma, Lycopi Herba, and Gardeniae Fructus, which were included in the Chinese Pharmacopoeia(2020 edition). The active ingredient quercetin mined from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) had ability to dock with the key gene FOS-encoded protein molecule, which provided targets and research ideas for the development of new traditional Chinese medicines.

Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin.@*METHODS@#A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43.@*RESULTS@#The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43.@*CONCLUSIONS@#The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Mechanisms mediating the inhibitory effects of quercetin against phthalates-induced testicular oxidative damage in rats / 南方医科大学学报

OBJECTIVE@#To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats.@*METHODS@#Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting.@*RESULTS@#Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05).@*CONCLUSION@#Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.