Protective effect of quercetin on lipopolysaccharide­induced miscarriage based on animal experiments and network pharmacology.

Spontaneous abortion (SA) occurs in woman of child­bearing age, jeopardizing their physical and mental health. Quercetin is a natural flavonoid, which exhibits a variety of pharmacological activities. However, the role and mechanisms of quercetin in SA still need to be further explored. Animal experiments were performed to examine the effect of quercetin in treating SA. Institute of Cancer Research mice were injected with lipopolysaccharide into the tail vein on the 7th day of gestation to establish a SA model. Gavage was performed during days 3­8 of gestation with high­, medium­ and low­dose of quercetin. Then the effect of quercetin on embryos was evaluated. Animal experiment showed that quercetin could remarkably reduce the embryo loss rate and increase the mean weight of surviving embryos to some degree. Furthermore, network pharmacology was employed to explore the underlying mechanisms of quercetin in the treatment of SA. Several databases were used to collect the targets of SA and quercetin. Protein­protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to elucidate the interactions between SA and quercetin. The relative mRNA expressions of several targets in uterine were detected by quantitative reverse transcriptase polymerase chain reaction (RT­qPCR). Network pharmacology indicated that the effects of quercetin in treating SA were mainly related to hormone response and the modulation of defense response and inflammatory response, involving signaling pathways such as PI3K­Akt, VEGF, MAPK and core targets such as AKT1, albumin, caspase­3. RT­qPCR showed that quercetin could up­regulate AKT1, MAPK1, PGR, SGK1 and down­regulate ESR1, MAPK3. The results showed that quercetin may modulate multiple signaling pathways by targeting core targets to prevent and treat SA.

Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis.

OBJECTIVES: The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. The antibacterial and antioxidant activities were determined in vitro. METHODS: The chemical constituents of GYS were detected by ultra-high-performance liquid chromatography Q-extractive mass spectrometry (UHPLC-QE-MS). Related compounds were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/) databases; genes associated with mastitis were identified in DisGENT. A protein-protein interaction (PPI) network was generated using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment screening was conducted using the R module. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. RESULTS: Fifty-four possible compounds in GYS with forty likely targets were found. The compound-target-network analysis showed that five of the ingredients, quercetin, luteolin, kaempferol, beta-sitosterol, and stigmasterol, had degree values >41.6, and the genes TNF, IL-6, IL-1ß, ICAM1, CXCL8, CRP, IFNG, TP53, IL-2, and TGFB1 were core targets in the network. Enrichment analysis revealed that pathways associated with cancer, lipids, atherosclerosis, and PI3K-Akt signaling pathways may be critical in the pharmacology network. Molecular-docking data supported the hypothesis that quercetin and luteolin interacted well with TNF-α and IL-6. CONCLUSIONS: An integrative investigation based on a bioinformatics-network topology provided new insights into the synergistic, multicomponent mechanisms of GYS's anti-inflammatory, antibacterial, and antioxidant activities. It revealed novel possibilities for developing new combination medications for reducing mastitis and its complications.

Antimicrobial Activity and Phytochemical Characterization of Baccharis concava Pers., a Native Plant of the Central Chilean Coast.

Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and near the Pacific coast. B. concava has been traditionally used by indigenous inhabitants of today's central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of B. concava. A hydroalcoholic extract of B. concava was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria, Candida albicans, and Cryptococcus neoformans but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to B. concava extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol-ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of B. concava showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.

Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer.

Background: The ChaiShao Shugan Formula (CSSGF) is a traditional Chinese medicine formula with recently identified therapeutic value in triple-negative breast cancer (TNBC). This study aimed to elucidate the underlying mechanism of CSSGF in TNBC treatment. Methods: TNBC targets were analyzed using R and data were from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The major ingredients and related protein targets of CSSGF were explored via the Traditional Chinese Medicine Systems Pharmacology database, and an ingredient-target network was constructed via Cytoscape to identify hub genes. The STRING database was used to construct the PPI network. GO and KEGG enrichment analyses were performed via R to obtain the main targets. The online tool Kaplan‒Meier plotter was used to identify the prognostic genes. Molecular docking was applied to the core target genes and active ingredients. MDA-MB-231 and MCF-7 cell lines were used to verify the efficacy of the various drugs. Results: A total of 4562 genes were screened as TNBC target genes. The PPI network consisted of 89 nodes and 845 edges. Our study indicated that quercetin, beta-sitosterol, luteolin and catechin might be the core ingredients of CSSGF, and EGFR and c-Myc might be the latent therapeutic targets of CSSGF in the treatment of TNBC. GO and KEGG analyses indicated that the anticancer effect of CSSGF on TNBC was mainly associated with DNA binding, transcription factor binding, and other biological processes. The related signaling pathways mainly involved the TNF-a, IL-17, and apoptosis pathways. The molecular docking data indicated that quercetin, beta-sitosterol, luteolin, and catechin had high affinity for EGFR, JUN, Caspase-3 and ESR1, respectively. In vitro, we found that CSSGF could suppress the expression of c-Myc or promote the expression of EGFR. In addition, we found that quercetin downregulates c-Myc expression in two BC cell lines. Conclusion: This study revealed the effective ingredients and latent molecular mechanism of action of CSSGF against TNBC and confirmed that quercetin could target c-Myc to induce anti-BC effects.

In silico study of alkaloids with quercetin nucleus for inhibition of SARS-CoV-2 protease and receptor cell protease.

Covid-19 disease caused by the deadly SARS-CoV-2 virus is a serious and threatening global health issue declared by the WHO as an epidemic. Researchers are studying the design and discovery of drugs to inhibit the SARS-CoV-2 virus due to its high mortality rate. The main Covid-19 virus protease (Mpro) and human transmembrane protease, serine 2 (TMPRSS2) are attractive targets for the study of antiviral drugs against SARS-2 coronavirus. Increasing consumption of herbal medicines in the community and a serious approach to these drugs have increased the demand for effective herbal substances. Alkaloids are one of the most important active ingredients in medicinal plants that have wide applications in the pharmaceutical industry. In this study, seven alkaloid ligands with Quercetin nucleus for the inhibition of Mpro and TMPRSS2 were studied using computational drug design including molecular docking and molecular dynamics simulation (MD). Auto Dock software was used to evaluate molecular binding energy. Three ligands with the most negative docking score were selected to be entered into the MD simulation procedure. To evaluate the protein conformational changes induced by tested ligands and calculate the binding energy between the ligands and target proteins, GROMACS software based on AMBER03 force field was used. The MD results showed that Phyllospadine and Dracocephin-A form stable complexes with Mpro and TMPRSS2. Prolinalin-A indicated an acceptable inhibitory effect on Mpro, whereas it resulted in some structural instability of TMPRSS2. The total binding energies between three ligands, Prolinalin-A, Phyllospadine and Dracocephin-A and two proteins MPro and TMRPSS2 are (-111.235 ± 15.877, - 75.422 ± 11.140), (-107.033 ± 9.072, -84.939 ± 10.155) and (-102.941 ± 9.477, - 92.451 ± 10.539), respectively. Since the binding energies are at a minimum, this indicates confirmation of the proper binding of the ligands to the proteins. Regardless of some Prolinalin-A-induced TMPRSS2 conformational changes, it may properly bind to TMPRSS2 binding site due to its acceptable binding energy. Therefore, these three ligands can be promising candidates for the development of drugs to treat infections caused by the SARS-CoV-2 virus.

Preparation of mesoporous silica/hydroxyapatite loaded quercetin nanoparticles and research on its antibacterial properties.

In this study, amino-functionalized mesoporous silica/hydroxyapatite nanoparticles (MSNS/HAP) with the property of acid dissociation have been prepared as a traditional Chinese medicine monomer carriers to improve the drug loading rate and antibacterial properties of antimicrobial quercetin (QUE) in vitro. The experimental results confirm that the drug loading rate of MSNs/HAP is 28.94 %, which is about 3.6 times higher than that of aminated mesoporous sililca nanoparticles (MSNs). The drug release of QUE on MSNs/HAP is pH-sensitive in phosphate buffered saline (pH=4.0-7.4). The above fabricated traditional Chinese medicine monomer modified nanocomposites (QUE@MSNs/HAP) displays concentration-dependent inhibitory effect, which shows better antibacterial effect than free QUE. The minimum inhibitory concentration for two tested bacteria, Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), is 256 mg·L -1. In summary, QUE@MSNs/HAP have successfully prepared, which not only improves the bio-availability of QUE, but also has acid-sensitive drug release properties. Compared with free QUE, its antibacterial performance significantly enhances, which provides a theoretical basis for the application of Chinese medicine molecules in bacterial treatment.

[Comparison of in vivo pharmacokinetics of twelve constituents in Qihe Fenqing Yin in normal rats and diabetic rats].

This paper aims to study the pharmacokinetic differences of twelve effective constituents(succinic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, protocatechuic aldehyde, caffeic acid, 5-O-ferulogeninic acid, p-coumaric acid, nuciferine, quercetin, oleanolic acid, and ursolic acid) in Qihe Fenqing Yin in normal and diabetic rats. The diabetic rat model was established by a high-fat diet combined with intraperitoneal injection of streptozocin. A UHPLC-QTRAP-MS/MS method was established for the simultaneous determination of 12 constituents in the plasma of normal rats and model rats after a single intragastric administration of Qihe Fenqing Yin. The results show that the established analytical method has a good linear relationship with the 12 components, and the specificity, accuracy, precision, and stability meet the requirements. The computational pharmacokinetic parameters are fitted by DAS 3.2.8 software, and the results show that the half-life time(t_(1/2)) of the other nine components in the model group was longer than that in the normal group except for caffeic acid, 5-O-ferulogeninic acid, and oleanolic acid. The area under curve(AUC_(0-t)) of cryptochlorogenic acid, p-coumaric acid, ursolic acid, and oleanolic acid increases compared with the normal group. Meanwhile, mean residence time(MRT) delays. The "double peaks" of quercetin and nuciferine in the normal group are not observed in the model group, suggesting that the pharmacokinetic parameters of the drugs in the disease state are significantly different.

Quercetin prophylaxis protects the kidneys by modulating the renin-angiotensin-aldosterone axis under acute hypobaric hypoxic stress.

The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.

In vitro Evaluation of Anti-Cancer Potential of Different Solvent Extracts Derived from Clerodendrum Infortunatum Linn against Cervical Cancer.

BACKGROUND: Cervical cancer is a prevalent and deadly malignancy in females, with chemotherapy often proving ineffective due to significant side effects and the development of chemo-resistance. This study investigates the medicinal potential of Clerodendrum infortunatum linn. , a genus with approximately 500 species in the Lamiaceae family. Limited research exists on the species of Clerodendrum infortunatum and its various solvent extracts. OBJECTIVE: The study aims to assess the anti-cancer properties of different solvent extracts from this plant on human cervical cancer cells. METHODS: The study examines the plant's phytochemical components and their potential to inhibit cancer growth. Aerial parts of the plant were extracted using the Soxhlet method, and the presence of Rutin, Quercetin, and Gallic Acid in specific solvent extracts was validated through High-Performance Thin Layer Chromatography (HPTLC). In vitro assays, including MTT, Apoptosis, Cell Cycle analysis, Intracellular Reactive Oxygen Species assessment, and Gene expression PCR, were conducted to investigate the plant's anti-cancer properties further. RESULTS: The outcomes of the phytochemical assessment indicated that Rutin was predominantly present in the water extract, with quercetin being more concentrated in the decoction, and the hydro-alcoholic extract showing elevated levels of gallic acid. Notably, the decoction extract demonstrated the highest cytotoxic activity, primarily through early apoptosis and arrests in the S-phase and G2M phases. Clerodendrum infortunatum exhibited a reduction in Intracellular Reactive Oxygen Species. The gene expression analysis disclosed an impact on the BCL-2 gene. CONCLUSION: Notably, Clerodendrum infortunatum exhibited the ability to initiate early apoptosis, halt the cell cycle at the S and G2M phases, and diminish levels of reactive oxygen species significantly. The gene expression analysis revealed an influence on the BCL-2 gene. To sum up, this research underscores the encouraging cytotoxic and antioxidant attributes of Clerodendrum infortunatum, implying its potential for cervical cancer treatment.

Essential oil composition, morphological characterization, phenolic content and antioxidant activity of Iranian populations of Hymenocrater longiflorus Benth. (Lamiaceae).

The study focused on the morphological and chemical characteristics of 200 Hymenocrater longiflorus Benth. genotypes found in natural habitats of eight regions in west of Iran. The primary objective of the study was to assess the morphological and phytochemical variability within populations grown in their natural habitats, with the aim of identifying their potential for domestication and utilization in pre-breeding programs. The plant height (PH) ranged from 50.32 to 69.65 cm, with the highest observed in population P8. The internode distances ranged from 4.7 to 6.47 cm, with the maximum distance found in P4. Flower lengths varied from 1.95 to 2.45 cm, with the minimum and maximum values observed in P4 and P3, respectively. The highest leaf length (5.20 cm) and width (3.87 cm) were recorded in P2. The aerial parts of the plant were utilized to extraction and determine the essential oil (EO) content and composition, which ranged from 0.40 to 0.78% (v/w). The analysis of EO by gas chromatography (GC) and gas chromatography mass spectrometry (GC/MS) identified 26 compounds, constituting 99-99.5% of the EOs. The main compounds in the EO and their percentage range (v/w DW) were tau-cadinol (0.62-55.56), mono (2-ethylhexyl) phthalate (8.10-94.70), elemol (0.21-19.11), ß-spathulenol (0.08-14.39), 4-terpineol (0.23-10.19), and ß-eudesmol (0.21-9.94). The main chemical groups found in EOs included oxygenated sesquiterpenes (1.12-68.43), and phthalates (9.73-94.72). Cluster analysis revealed three distinct chemotypes: chemotype I (populations 1 and 2) with major components of mono (2-ethylhexyl) phthalate, tau-cadinol, and α-elemol; chemotype II (population 5) rich in mono (2-ethylhexyl) phthalate; and chemotype III (populations 3, 4, 6-8) containing tau-cadinol, ß-eudesmol, and 4-terpineol. The study also evaluated total phenolic, total flavonoid, and DPPH free radical scavenging activity in the fifty percent inhibitory concentration (IC50) in leaf and flower samples of the genotypes, along with estimating total anthocyanin content in the flower samples. The total phenolic content (TPC) in leaf and flower samples ranged from 7.89 to 107.18 mg GAE/g DW and 39.98 to 86.62 mg gallic acid equivalent (GAE)/g DW, respectively. Total flavonoid content (TFC) ranged from 81.04 to 143.46 mg QUE/g DW in leaf samples and from 94.82 to 133.26 mg quercetin equivalent (QUE)/g DW in flower samples. DPPHsc IC50 (µg/mL) ranged from 0.65 to 78.74 in leaf samples and from 4.38 to 7.71 in flower samples. Anthocyanin content ranged from 1.89 to 3.75 mg cyanidin-3-glucoside equivalent (C3GE)/g DW among populations. Canonical correspondence analysis and simple correlation demonstrated a strong association and correlations among the studied attributes. The negative correlations between leaf DPPH (DPPH L) IC50 and TFC (- 0.73), TPC (- 0.63), Elemol (- 0.90), and EO (- 0.85) indicate that these compounds have a significant impact on the antioxidant activity of the leaves. Furthermore, Fruit DPPH (DPPH F) IC50 showed a negative correlation with TPC (- 0.79) and TFC (- 0.78), but a positive correlation with flower anthocyanins (0.51), (Z)-ß-Farnesene (0.66), and 4-Terpineol (0.57). Circular cluster analysis categorized the genotypes of all individuals in the eight studied populations into three main categories based on all the studied traits, indicating significant variation in phytochemical and morphological traits among populations, surpassing the within-populations variation.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

Phytochemical quantification and HPLC analysis of Parkia speciosa pod extract.

INTRODUCTION: Parkia speciosa Hassk., commonly known as bitter bean or twisted cluster bean, is a tropical leguminous plant species native to Southeast Asia. The plant's edible pods have been traditionally used in various cuisines, particularly in Malaysian, Thai, and Indonesian cooking. Apart from being used as a food ingredient, the pods of P. speciosa also have a range of potential applications in other fields, including medicine, agriculture, and industry. The pods are said to have several phytochemicals that hold great therapeutic values such as reducing inflammation, improving digestion, and lowering blood sugar levels. However, there is limited information on the specific phytochemical contents of the pods in the literature. Thus, the aim of this study is to quantify the total phenolic and flavonoid compounds and to determine the concentrations of four selected phytochemical compounds in the P. speciosa pod extract (PSPE). MATERIALS AND METHODS: Quantification of the total phenolic (TPC) and flavonoid contents (TFC) in PSPE were done via colourimetric methods; and the determination of the concentrations of four specific phytochemicals (gallic acid, caffeic acid, rutin, and quercetin) were done via High- Performance Liquid Chromatography (HPLC). RESULTS: Colourimetric determination of PSPE showed TPC and TFC values of 84.53±9.40 mg GAE/g and 11.96±4.51 mg QE/g, respectively. Additional analysis of the phytochemicals using HPLC revealed that there were 6.45±3.36 g/kg, 5.91±1.07 g/kg, 0.39±0.84 g/kg, and 0.19±0.47 g/kg of caffeic acid, gallic acid, rutin, and quercetin, respectively. CONCLUSION: The findings show that PSPE contains substantial amounts of caffeic acid, gallic acid, rutin, and quercetin, which may indicate its potential as antibacterial, anti-inflammatory, anti-lipid, and antiviral medicines.

Overview of alkyl quercetin lipophenol synthesis and its protective effect against carbonyl stress involved in neurodegeneration.

Oxidative stress and carbonyl stress resulting from the toxicity of small aldehydes are part of the detrimental mechanisms leading to neuronal cell loss involved in the progression of neurodegenerative diseases such as Alzheimer's disease. Polyunsaturated alkylated lipophenols represent a new class of hybrid molecules that combine the health benefits of anti-inflammatory omega-3 fatty acids with the anti-carbonyl and oxidative stress (anti-COS) properties of (poly)phenols in a single pharmacological entity. To investigate the therapeutic potential of quercetin-3-docosahexaenoic acid-7-isopropyl lipophenol in neurodegenerative diseases, three synthetic pathways using chemical or chemo-enzymatic strategies were developed to access milligram or gram scale quantities of this alkyl lipophenol. The protective effect of quercetin-3-DHA-7-iPr against cytotoxic concentrations of acrolein (a carbonyl stressor) was assessed in human SHSY-5Y neuroblastoma cells to underscore its ability to alleviate harmful mechanisms associated with carbonyl stress in the context of neurodegenerative diseases.

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],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[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] 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[Formula: see text] 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[Formula: see text] 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.

In silico and in vivo study of anti-inflammatory activity of Morinda longissima (Rubiaceae) extract and phytochemicals for treatment of inflammation-mediated diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-ß-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

Protective Effects of Aspirin Supplemented With Quercetin in L-NAME-Induced Preeclampsia-Like Rats.

Aspirin supplemented with quercetin was reported to enhance the therapeutic effects of aspirin in a rat model of preeclampsia. In this study, the underlying mechanisms were further explored. Preeclampsia was induced by L-NAME (50 mg/kg/day) via oral gavage from gestation day (GD)14 to GD19. Aspirin (1.5 mg/kg/day) administration was performed using aspirin mixed with rodent dough from GD0 to GD19. The administration of quercetin (2 mg/kg/day) was performed by intraperitoneal infusion from GD0 to GD19. Protein levels were evaluated using ELISA or Western blot, and microRNA (miRNA) level was evaluated by RT-PCR. Aspirin supplemented with quercetin ameliorated the increase of systolic blood pressure (SBP), proteinuria, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, and improved the pregnancy outcomes in preeclampsia rats. Aspirin supplemented with quercetin inhibited miR-155 expression in preeclampsia rats. The decreased miR-155 level in placenta further increased the protein level of SOCS1 and inhibited the phosphorylation of p65. In this study, we demonstrated that aspirin supplemented with quercetin enhanced the effects of aspirin for the treatment of preeclampsia.

Ultrasound-mediated host-guest self-assembly between different dietary fatty acids and sodium caseinate and their complexes improving the water dispersibility, stability, and bioaccessibility of quercetin.

Quercetin (QUE) sufferred from poor processing adaptability and absorbability, hindering its application as a dietary supplement in the food industry. In this study, fatty acids (FAs)-sodium caseinate (NaCas) ligand complexes carriers were fabricated to improve the aqueous dispersibility, storage/thermal stability, and bioaccessibility of QUE using an ultrasound method. The results indicated that all six selected common dietary FAs formed stable hydrophilic complexes with NaCas and the FAs-NaCas complexes achieved an encapsulation efficiency greater than 90 % for QUE. Furthermore, the introduction of FAs enhanced the binding affinity between NaCas and QUE, but did not change the binding mode (static bursting) and types of intermolecular forces (mainly hydrogen bonding). In addition, a distinct improvement was discovered in the storage stability (>2.37-fold), thermal processing stability (>32.54 %), and bioaccessibility (>2.37-fold) of QUE. Therefore, the FAs-NaCas ligand complexes could effectively protect QUE to minimize degradation as fat-soluble polyphenol delivery vehicles.

Liquid chromatography-mass spectrometry-based strategy for systematic profiling of chemical components and associated quantitative analysis of quality markers in Qi-Wei-Tong-Bi oral liquid.

Qi-Wei-Tong-Bi oral liquid (QWTB), a famous Chinese medicine preparation composed of seven crude drugs has a good therapeutic effect on rheumatoid arthritis and is widely used in China. However, its chemical composition and quality control have not been comprehensively and systematically investigated. In this study, high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed for its chemical profiling. As a result, 100 components were chemically characterized. Additionally, high-performance liquid chromatography coupled with a quadrupole linear ion trap mass spectrometry method was developed to simultaneously quantify nine bioactive components (hyperoside, ononin, quercetin, sinomenine, magnoflorine, gallic acid, protocatechuic acid, monotropein, and cyclo-(Pro-Tyr)) in multiple-reaction monitoring mode. After successful validation in terms of linearity, precision, repeatability, and recovery, the assay method was applied for the determination of 10 batches of QWTB. The results showed that QWTB was enriched in sinomenine and magnoflorine with the highest amount up to hundreds or even thousands of µg/mL, while quercetin, ononin, cyclo-(Pro-Tyr), and hyperoside were much lower with the lowest content below 10 µg/mL. This study work would help to reveal the chemical profiling and provide a valuable and reliable approach for quality evaluation and even pharmacodynamic material basis studies of QWTB.

Ethanol-Induced Hepatic Ferroptosis Is Mediated by PERK-Dependent MAMs Formation: Preventive Role of Quercetin.

SCOPE: Iron deposition is frequently observed in alcoholic liver disease (ALD), which indicates a potential role of ferroptosis in its development. This study aims to explore the effects of quercetin on ferroptosis in ALD and elucidates the underlying mechanism involving the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) mediated by protein kinase RNA-like endoplasmic reticulum kinase (PERK). METHODS AND RESULTS: C57BL/6J mice are fed either a regular or an ethanol-containing liquid diet (with 28% energy form ethanol) with or without quercetin supplementation (100 mg kg-1 BW) for 12 weeks. Ethanol feeding or treatment induced ferroptosis in mice and AML12 cells, which is associated with increased MAMs formation and PERK expression within MAMs. Quercetin attenuates these changes and protects against ethanol-induced liver injury. The antiferroptotic effect of quercetin is abolished by ferroptosis inducers, but mimicked by ferroptosis inhibitors and PERK knockdown. The study demonstrates that PERK structure, rather than its kinase activity (transfected with the K618A site mutation that inhibits kinase activity-ΔK plasmid or protein C terminal knockout-ΔC plasmid of PERK), mediates the enhanced MAMs formation and ferroptosis during the ethanol exposure. CONCLUSION: Quercetin ameliorates ethanol-induced liver injury by inhibiting ferroptosis via modulating PERK-dependent MAMs formation.

"Plant Golden" C. sativus: Qualitative and quantitative analysis of major components in stigmas and petals and their biological activity in vitro.

Crocus sativus L. (C. sativus) has its stigma as the main valuable part used. With extremely low production and high prices, stigma is considered a scarce resource. As a result, its petals, considered as by-products, are often discarded, leading to significant waste. We developed a UPLC-Q-Orbitrap HRMS method for qualitative analysis of stigmas and petals and a UHPLC-QQQ-MS/MS method for simultaneous quantification of 9 characteristic active compounds for the first time, and compared their biological activity in vitro. The results indicated that a total of 63 compounds were identified in the petals and stigmas. The content of flavonoids in the petals was significantly superior to that in the stigma, and the content of quercetin in the petals was 50 times higher than that in the stigma. The results of the in vitro evaluation of biological activity indicated that both the petals （•OH: IC50=39.70 mg/mL; DPPH: IC50=28.37 mg/mL; ABTS: IC50=0.9868 mg/mL）and stigma （•OH: IC50=34.41 mg/mL; DPPH: IC50=38.99 mg/mL; ABTS: IC50=3.194 mg/mL）demonstrated comparable antioxidant activities. However, the tyrosinase inhibitory activity in petals （IC50=21.17 mg/mL） was weaker than that in stigma（IC50=1.488 mg/mL）. This study provides a fast, reliable, and efficient analytical method that can be used for the quality assessment of petals as a natural resource and its related products in the food and pharmaceutical industries.