RESUMEN

Luteolin-7-O-glucoside(L7G), a glycosylation product of luteolin, is present in a variety of foods, vegetables, and medicinal herbs and is commonly used in dietary supplements due to its health benefits. Meanwhile, luteolin-7-O-glucoside is an indicator component for the quality control of honeysuckle in the pharmacopoeia. However, its low content in plants has hindered its use in animal pharmacological studies and clinical practice. In this study, a novel 7-O-glycosyltransferase CmGT from Cucurbita moschata was cloned, which could efficiently convert luteolin into luteolin-7-O-glucoside under optimal conditions (40 °C and pH 8.5). To further improve the catalytic efficiency of CmGT, a 3D structure of CmGT was constructed, and directed evolution was performed. The mutant CmGT-S16A-T80W was obtained by using alanine scanning and iterative saturation mutagenesis. This mutant exhibited a kcat/Km value of 772 s-1·M-1, which was 3.16-fold of the wild-type enzyme CmGT. Finally, by introducing a soluble tag and UDPG synthesis pathway, the strain BXC was able to convert 1.25 g/L of luteolin into 1.91 g/L of luteolin-7-O-glucoside under optimal conditions, achieving a molar conversion rate of 96% and a space-time yield of 27.08 mg/L/h. This study provides an efficient method for the biosynthesis of luteolin-7-O-glucoside, which holds broad application prospects in the food and pharmaceutical industry.

Asunto(s)

Biocatálisis , Cucurbita , Glucósidos , Glicosiltransferasas , Luteolina , Proteínas de Plantas , Glucósidos/metabolismo , Glucósidos/química , Glucósidos/biosíntesis , Luteolina/química , Luteolina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Glicosiltransferasas/química , Cucurbita/genética , Cucurbita/enzimología , Cucurbita/química , Cucurbita/metabolismo , Clonación Molecular , Cinética , Evolución Molecular Dirigida

RESUMEN

Cancer is responsible for approximately 10 million deaths worldwide, with 70% of the deaths occurring in low- and middle-income countries; as such safer and more effective anti-cancer drugs are required. Therefore, the potential benefits of Ziziphus nummularia and Ziziphus spina-christi as sources of anti-cancer agents were investigated. Z. nummularia and Z. spina-christi extracts were prepared using chloroform, ethanol, ethyl acetate, and water. The extracts' anti-cancer properties were determined using the MTT Cell Viability Assay in four cancer cell lines: breast (KAIMRC2 and MDA-MB-231), colorectal (HCT8), and liver (HepG2). The ApoTox-Glo Triplex Assay and high-content imaging (HCI)-Apoptosis Assay were used to assess KAIMRC2 and HCT8 cells further. In addition, KAIMRC2 cells were tested for microtubule staining, and AKT/mTOR protein expression was determined by western blot analysis. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the secondary metabolites in the ethanol and ethyl acetate extracts, followed by in silico techniques to predict molecular targets and interactions, safety, and pharmacokinetic profile for identified metabolites. Out of the eight extracts, the ethanolic extract of Z. nummularia, exhibited the most potent activity against KAIMRC2 cells with an IC50 value of 29.2 µg/ml. Cancer cell treatment with the ethanolic extract of Z. nummularia resulted in a dose-dependent decrease in cell viability with increased apoptosis and cytotoxic effects. Microtubule staining showed a disrupted microtubular network. The ethanolic extract treatment of KAIMRC2 cells led to upregulated expression of pAKT and pmTOR. In silico studies predicted luteolin-7-O-glucoside to be a ligand for tubulin with the highest docking score (- 7.686) and similar binding interactions relative to the native ligand. Further computational analysis of the metabolites showed acceptable pharmacokinetic and safety profiles, although ethanolic extract metabolites were predicted to have cardiotoxic effects. Ethanolic extraction is optimal for solubilizing active anticancer metabolites from Z. nummularia, which may act by causing M-phase arrest via inhibition of tubulin polymerization. Luteolin-7-O-glucoside is the lead candidate for further research and development as an anti-cancer agent. In addition, this study suggests that herbal treatment could switch on mechanisms of adaptation and survival in cancer cells.

Asunto(s)

Acetatos , Glucósidos , Luteolina , Neoplasias , Ziziphus , Extractos Vegetales/farmacología , Ziziphus/química , Moduladores de Tubulina , Ligandos , Tubulina (Proteína) , Etanol

RESUMEN

Respiratory syncytial virus (RSV) pneumonia is the main cause of acute bronchiolitis in infants. Luteolin-7-O-glucoside (LUT-7G) is a natural flavonoid, which exists in a variety of plants and has the potential to treat viral pneumonia. We established RSV pneumonia mouse models and RSV-infected cell models. Clodronate liposomes were used to deplete macrophages. We used HE staining and immunohistochemistry to determine inflammatory damage and virus replication. We detected the expression levels of inflammatory factors and IFN-ß through qPCR and ELISA. JC-1 kit was used for detecting the cell mitochondrial Membrane potential (MMP). ROS, SOD, and MDA kits were used for detecting intracellular oxidative stress damage. Metabolites of TCA in lung tissue and serum of mice were detected by GC-MS. Pharmacodynamic studies have shown that intervention with LUT-7G can alleviate lung tissue damage caused by RSV infection, inhibit RSV replication, and downregulate TNF-α, IL-1ß, and IL-6 mRNA expression. LUT-7G upregulated the IFN-ß content and the expression of IFN-ß, ISG15, and OAS1 mRNA. In vitro, LUT-7G inhibited RSV-induced cell death, reversed the RSV-induced decrease of MMP and decreased intracellular oxidative stress. Target metabonomics showed that RSV infection upregulated the levels of glycolysis and TCA metabolites in lung tissue and serum, while LUT-7G could improve the disorder of glucose metabolism. The results indicate that LUT-7G can promote the release of IFN-ß in the lung, alleviate inflammatory damage, and inhibit RSV replication during RSV infection. These effects may be achieved by protecting the mitochondrial function of alveolar macrophages and correcting the disorder of glucose metabolism.

Asunto(s)

Interferón beta , Luteolina , Mitocondrias , Infecciones por Virus Sincitial Respiratorio , Animales , Humanos , Ratones , Glucosa/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Neumonía/metabolismo , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/genética , Infecciones por Virus Sincitial Respiratorio/metabolismo , ARN Mensajero , Luteolina/farmacología , Interferón beta/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo

RESUMEN

Gentianopsis is a small gentianaceous genus with a known ethnopharmacological focus as hepatoprotectors containing two underestimated species that are scientifically unexplored: Gentianopsis komarovii (Grossh.) Toyok., which is typical of the Far East, and Gentianopsis stricta (Klotzsch) Ikonn., which is grown in Central Asia. Application of the HPLC-PDA-ESI-tQ-MS/MS technique led to the identification of 28 compounds, such as iridoid glycosides, flavones and xanthones, with loganic acid, sweroside, loganin, secologanin, isoorientin-7-O-glucoside, luteolin-7-O-gentiobioside, chrysoeriol-7-O-glucoside and acacetin-7-O-glucoside being found in the genus for the first time. The extracts of G. komarovii and G. stricta demonstrated choleretic potential, strengthening the bile flow and the total content of bile acids, bilirubin and cholesterol in the bile. The most pronounced effects were observed for luteolin-7-O-glucoside and gentiabavaroside (gentiacaulein-1-O-primveroside), establishing them as the principle choleretics of both herbs. Based on the results, G. komarovii, G. stricta and some phenolic metabolites are prospective new choleretic drugs.

Asunto(s)

Colagogos y Coleréticos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Glucósidos/farmacología , Fenoles/análisis , Extractos Vegetales/farmacología

RESUMEN

Luteolin derivates are plant compounds with multiple benefits for human health. Stability to heat and acid hydrolysis and high resistance to (auto)oxidation are other arguments for the laden interest in luteolin derivates today. The present study was designed to compare the in silico and in vitro anti-proliferative potential of two luteolin derivates, luteolin-7-O-glucoside/cynaroside (7-Lut) and luteolin-8-C-glucoside/orientin (8-Lut). In silico investigations were carried out on the molecular target, namely, the human dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) in association with its natural ligand, curcumin (PDB ID: 5ZTN), by CLC Drug Discovery Workbench v. 1.5.1. software and Molegro Virtual Docker (MVD) v. MVD 2019.7.0. software. In vitro studies were performed on two human tumor cell lines, glioblastoma (U87) and colon carcinoma (Caco-2), respectively. Altogether, docking studies have revealed 7-Lut and 8-Lut as effective inhibitors of DYRK2, even stronger than the native ligand curcumin; in vitro studies indicated the ability of both luteolin glucosides to inhibit the viability of both human tumor cell lines, up to 85% at 50 and 100 µg/mL, respectively; the most augmented cytotoxic and anti-proliferative effects were obtained for U87 exposed to 7-Lut (IC50 = 26.34 µg/mL). The results support further studies on cynaroside and orientin to create drug formulas targeting glioblastoma and colon carcinoma in humans.

Asunto(s)

Antineoplásicos , Carcinoma , Curcumina , Glioblastoma , Humanos , Células CACO-2 , Glioblastoma/patología , Glucósidos/farmacología , Ligandos , Luteolina/farmacología , Antineoplásicos/farmacología

RESUMEN

Raoultella ornithinolytica is an Enterobacteriaceae bacterium that can infect both humans and animals, while luteolin-7-O-glucoside (IOG) is a flavonoid that has broad effects on the intestinal microbiota of healthy animals. However, current studies lack sufficient data on intestinal microbiota dysbiosis and drug resistance transmission caused by R. ornithinolytica and the possible role of IOG. In this study, BALB/c mice were infected with R. ornithinolytica carrying blaNDM-1 gene and treated with IOG (3 mg/kg·d and 6 mg/kg·d) to analyze the diversity of intestinal microbiota and the transfer of blaNDM-1 between bacteria. The findings indicated that R. ornithinolytica B1645-1 exhibited a significant ability to enhance the Firmicutes/Bacteroidota ratio and increase the relative abundance of Lactobacillus and Bacillus after 48 h, where as 6 mg/kg·d IOG had an opposite effect. Moreover, R. ornithinolytica B1645-1 facilitated the emergence of drug-resistant bacteria and promoted blaNDM-1 gene transfer in Enterococcus, Escherichia, Klebsiella, Acinetobacter, Bacillus, Brevibacterium, and Lactobacillus. Enterococcus was the predominant genus at 48 h. Surprisingly, 6 mg/kg·d IOG significantly inhibited the production of drug-resistant bacteria and promoted blaNDM-1 gene transfer from Enterococcus to Lactobacillus at 144 h. However, the role of Lactobacillus as a recipient for drug-resistant genes should be of more concern.

RESUMEN

The genus Crepis constitutes cold-adapted plant spp., of these some are traditionally used in folk medicine against inflammation or fungal infections without scientific validations. Here, we report the biological activities of Crepis flexuosa total ethanol-extract (CF-EtOH) and its hexane (CF-Hex), ethyl acetate (CF-EtOA), butanol (CF-ButOH), and aqueous (CF-Aqua) fractions. Our in vitro DPPH and ABTS radical-scavenging assays showed CF-EtOH, CF-ButOH and CF-Aqua with maximal, CF-EtOA with moderate, and CF-Hex with mild anti-oxidant activities. When tested on human cancer cell lines, high cytotoxicity was demonstrated by CF-EtOH (IC50: 42.45 µg/ml) and CF-Aqua (IC50: 46.37 µg/ml) on HepG2, followed by CF-Hex (IC50: 63.24 µg/ml) and CF-ButOH (IC50: 65.32 µg/ml) on MCF7 cells. The human primary cell line (HUVEC) had comparatively lower cytotoxicity for the tested samples. Moreover, when assessed for anti-microbial efficacy, CF-ButOH and CF-Aqua exhibited the strongest activity (MIC: 156.25 µg/ml) against S. aureus, E. faecalis and C. albicans. Further, while the developed RP-HPTLC identified the bioactive flavonoid luteolin-7-O-glucoside (17.58 mg/g), GS/MS analysis revealed sixteen compounds in C. flexuosa extract. In conclusion, we for the first time show the promising anti-oxidative, anti-cell proliferative and anti-microbial efficacies of C. flexuosa. This warrants further phytochemical and bio-efficacy studies towards isolations and identifications of active principles.

RESUMEN

Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, and other organoleptic characteristics, as well as contributing to important nutritional aspects. Beyond these characteristics, due to their biochemical properties and characteristics, they can be considered bioactive compounds. Several interesting studies have demonstrated their biological activity in different cellular and physiological processes in high-order organisms including humans. The flavonoid molecular structure confers the capability of reacting with and neutralizing reactive oxygen species (ROS), behaving as scavengers in all processes generating this class of molecules, such as UV irradiation, a process widely present in plant physiology. Importantly, the recent scientific literature has demonstrated that flavonoids, in human physiology, are active compounds acting not only as scavengers but also with the important role of counteracting the inflammation process. Among the wide variety of flavonoid molecules, significant results have been shown by investigating the role of the flavones luteolin and luteolin-7-O-glucoside (LUT-7G). For these compounds, experimental results demonstrated an interesting anti-inflammatory action, both in vitro and in vivo, in the interaction with JAK/STAT3, NF-κB, and other pathways described in this review. We also describe the effects in metabolic pathways connected with inflammation, such as cellular glycolysis, diabetes, lipid peroxidation, and effects in cancer cells. Moreover, the inhibition of inflammatory pathway in endothelial tissue, as well as the NLRP3 inflammasome assembly, demonstrates a key role in the progression of such phenomena. Since these micronutrient molecules can be obtained from food, their biochemical properties open new perspectives with respect to the long-term health status of healthy individuals, as well as their use as a coadjutant treatment in specific diseases.

Asunto(s)

Antiinflamatorios , Luteolina , Antiinflamatorios/farmacología , Flavonoides/farmacología , Glucósidos/química , Glucósidos/farmacología , Humanos , Inflamación/tratamiento farmacológico , Luteolina/química , Luteolina/farmacología

RESUMEN

Olea europaea L. is a plant belonging to the Oleaceae family, widely grown around the Mediterranean Basin and its leaves are a source of phenolic compounds with antioxidant and anti-inflammatory capacity. Among these, oleuropein and luteolin-7-O-glucoside represent two major polyphenolic compounds in olive-leaf extract. Herein, a polystyrene resin was used to recover the polyphenolic fraction from the acetone-water leaf extract from Nocellara del Belice cultivar, which showed the higher level of analysed bioactive compounds, compared to Carolea cultivar. The antioxidant activity of the extract concentrated in phenolic compounds (OLECp) was evaluated through a classical assay and electron paramagnetic resonance (EPR) for DPPH and hydroxyl radicals scavenging. Thus, the anti-inflammatory activity and the potential beneficial effects in reducing lipid accumulation in an in vitro model of NAFLD using McA-RH7777 cells exposed to oleic acid (OA) were evaluated. Nile Red and Oil Red O have been used to stain the lipid accumulation, while the inflammatory status was assessed by Cytokines Bioplex Assay. OLECp (TPC: 92.93 ± 9.35 mg GAE/g, TFC: 728.12 ± 16.04 mg RE/g; 1 g of extract contains 315.250 mg of oleuropein and 17.44 mg of luteolin-7-O-glucoside) exerted a good radical scavenging capability (IC50: 2.30 ± 0.18 mg/mL) with a neutralizing power against DPPH and hydroxyl radicals, as confirmed by the decreased signal area of the EPR spectra. Moreover, OLECp at concentration of 25, 50 and 100 µg/mL counteracted the intracellular inflammatory status, as result of decreased intracellular lipid content. Our results highlighted the multiple properties and applications of an O. europaea extract concentrated in polyphenols, and the possibility to formulate novel nutraceuticals with antioxidant properties, destined to ameliorate human health.

RESUMEN

In this study, the chemical content of the threatened Cretan endemic Chaerophyllum creticum Boiss. & Heldr. was investigated by High Performance Liquid chromatography-Photodiode Array-Mass Spectrometry (HPLC-PDA-MS) analysis. Leaves, flowers and stems of C. creticum, were extracted via maceration and were assessed for their polyphenolic composition and antioxidant capacity. The highest extraction yields were achieved by methanol and methanol/water. A total of 17 compounds were characterised in C. creticum with luteolin-7-O-glucoside being the predominant glucoside found in all the extracts. Malonic esters were present in all the extracts. The main flavonoids and phenolics were quantified by HPLC-UV in parallel to standard spectrophotometric assays which were used for the determination of the Total Polyphenol content and the Total Flavonoid Content. The antioxidant activity was assessed by two different tests: 2,2-diphenyl-1-picrylhydrazyl (DPPH•) free radical assay and the ferric reducing antioxidant power (FRAP) assay. This is the first report on the chemical content of the Cretan endemic C. creticum.

Asunto(s)

Antioxidantes , Metanol , Animales , Antioxidantes/química , Cromatografía Líquida de Alta Presión/métodos , Especies en Peligro de Extinción , Flavonoides/química , Espectrometría de Masas/métodos , Fenoles/análisis , Extractos Vegetales/química

RESUMEN

Nasopharyngeal carcinoma (NPC) is an unnoticeable malignant tumor with a high potential of lymphatic metastasis, and its prevalence is high in Asia. Ionizing radiation is the mainstay of treatment for patients with NPC without metastasis. However, patients with metastatic lesions require advanced treatments such as chemotherapy. The present study investigated the apoptotic effect of luteolin-7-O-glucoside on NPC cells and elucidated its underlying signaling mechanisms. The results revealed that luteolin-7-O-glucoside significantly reduced the proliferation of NPC cell lines (NPC-039 and NPC-BM). Flow cytometry and morphological analysis results demonstrated that luteolin-7-O-glucoside treatment induced S and G2 /M cell cycle arrest, chromatin condensation, and apoptosis. In addition, mitochondrial membrane potential was observed to be depolarized with an increasing concentration of luteolin-7-O-glucoside. Proteins involved in the extrinsic and intrinsic pathways of apoptosis, such as death receptor, caspase-3, caspase-8, caspase-9, and Bcl-2 family proteins (Bax, t-Bid, Bcl-2, and Bcl-xL), were downregulated and upregulated after treatment with luteolin-7-O-glucoside, respectively. Moreover, the addition of a PI3K/AKT inhibitor enhanced the activation of poly-ADP-ribose-polymerase (PARP) and attenuated cell viability, indicating that luteolin-7-O-glucoside induced apoptosis in NPC cells through the AKT signaling pathway. These results indicated that the apoptosis of NPC cells modulated by luteolin-7-O-glucoside may be preceded by mitochondrial depolarization, cell cycle arrest, extrinsic and intrinsic apoptosis pathway activation, and AKT signaling modulation. Thus, luteolin-7-O-glucoside can be a promising anticancer agent against human NPC.

Asunto(s)

Neoplasias Nasofaríngeas , Proteínas Proto-Oncogénicas c-akt , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Flavonas , Glucósidos , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal

RESUMEN

Flavonoids display a broad range of structures and are responsible for the major organoleptic characteristics of plant-derived foods and beverages. Recent data showed their activity, and in particular of luteolin-7-O-glucoside (LUT-7G), in reduction of oxidative stress and inflammatory mechanisms in different physiological systems. In this paper, we tried to elucidate how LUT-7G could exert both antioxidant and anti-inflammatory effects in endothelial cells cultured in vitro. Here, we showed that LUT-7G is able to inhibit the STAT3 pathway, to have an antiproliferative action, and an important antioxidant property in HUVEC cells. These properties are exerted by the flavone in endothelial through the transcriptional repression of a number of inflammatory cytokines and their receptors, and by the inhibition of ROS generation. ROS and STAT3 activation has been correlated with the production of oxysterols and other hydroxylated fatty acids, and they have been recognized important as players of atherogenesis and cardiocirculatory system diseases. The analysis of the general production pathway of these hydroxylated species, showed a strong decrease of cholesterol hydroxylated species such as 7-alpha-hydroxicholesterol, 7-beta-hydroxicholesterol by the treatment with LUT-7G. This confirms the anti-inflammatory properties of LUT-7G also in the endothelial district, showing for the first time the molecular pathway that verify previous postulated cardiovascular benefits of this flavone.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Flavonas/farmacología , Glucósidos/farmacología , Queratinocitos/citología , Sialiltransferasas/metabolismo , Línea Celular , Proliferación Celular , Células Endoteliales/química , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Ácidos Grasos/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hidroxilación , Queratinocitos/química , Queratinocitos/efectos de los fármacos , Metabolómica , Oxiesteroles/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Oral squamous cell carcinoma is the sixth most common type of cancer globally, which is associated with high rates of cancer-related deaths. Metastasis to distant organs is the main reason behind worst prognostic outcome of oral cancer. In the present study, we aimed at evaluating the effects of a natural plant flavonoid, luteolin-7-O-glucoside, on oral cancer cell migration and invasion. The study findings showed that in addition to preventing cell proliferation, luteolin-7-O-glucoside caused a significant reduction in oral cancer cell migration and invasion. Mechanistically, luteolin-7-O-glucoside caused a reduction in cancer metastasis by reducing p38 phosphorylation and downregulating matrix metalloproteinase (MMP)-2 expression. Using a p38 inhibitor, SB203580, we proved that luteolin-7-O-glucoside exerts anti-migratory effects by suppressing p38-mediated increased expression of MMP-2. This is the first study to demonstrate the luteolin-7-O-glucoside inhibits cell migration and invasion by regulating MMP-2 expression and extracellular signal-regulated kinase pathway in human oral cancer cell. The study identifies luteolin-7-O-glucoside as a potential anti-cancer candidate that can be utilized clinically for improving oral cancer prognosis.

Asunto(s)

Carcinoma de Células Escamosas/tratamiento farmacológico , Flavonas/farmacología , Glucósidos/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Imidazoles/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias de la Boca/patología , Piridinas/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo

RESUMEN

Olive leaves are considered a promising source of bioactives such as phenolic compounds and mannitol. The extraction of high added value products is an issue of great interest and importance from the point of view of their exploitation. However, the content of these compounds can differ between cultivars and extraction methods. In this work, six olive leaves cultivars, including three wild cultivars, and two extraction processes (an innovative and alternative technique, pressurized liquid extraction, and a conventional Soxhlet extraction) were evaluated and compared towards the selective recovery of bioactive compounds. The wild cultivars showed the highest content of phenolic and flavonoid compounds, being oleuropein the compound present in higher amount. Findings also revealed that the highest mannitol content in the extracts was observed with the commercial cultivars, specifically in Arbequina. It is thus possible to decide which cultivars to use in order to obtain the highest yield of each bioproduct.

Asunto(s)

Manitol/análisis , Olea/química , Fenoles/análisis , Extractos Vegetales/química , Flavonoides/análisis , Glucósidos Iridoides , Iridoides/análisis , Hojas de la Planta/química , Presión , España

RESUMEN

Cisplatin is an effective chemotherapeutic agent that has pronounced adverse effects. Using flavonoids is currently eliciting considerable interest. During extraction and conditioning, they usually undergo several physical treatments such as heat treatment, although it is not known whether thermal treatment might influence the pharmacological effects of flavonoids such as luteolin-7-O-glucoside (L7G). This study was undertaken to explore the protective role of native and heated L7G against DNA damage and oxidative stress induced by cisplatin. Balb/c mice were administered L7G before a single intraperitoneal injection of cisplatin (10 mg/kg). Animals were sacrificed 24 h after treatment with drugs. The geno-protective role of native and heated L7G was evaluated by comet assay. In addition to monitoring the activities of antioxidant enzymes, levels of malondialdehyde and reduced glutathione were assessed in the liver, kidney, brain, and spleen tissues. The results of the present study demonstrate that both heated and native L7G, at a dose of 40 mg/kg b.w, were able to reduce the genotoxicity of cisplatin. They attenuate the oxidative stress (malondialdehyde, catalase, GPx, SOD, and GSH) and tissue damage (creatinine, IFNγ). Heat treatment did not alter the antigenotoxic effect observed for native L7G and showed similar effects to those of native L7G for all of the evaluated parameters. Our study reveals that L7G attenuates the side effects of anticancer drug and heat treatment did not alter his antigenotoxic and antioxidant the potential.

Asunto(s)

Antineoplásicos/farmacología , Cisplatino , Animales , Antioxidantes , Daño del ADN , Flavonas , Glucósidos , Glutatión , Calor , Riñón , Ratones , Estrés Oxidativo/efectos de los fármacos

RESUMEN

BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and 10 µg/kg BW, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and TNF-α levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor (NF)-κB and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.

RESUMEN

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Accumulating evidences implicate the beneficial role of estrogen in the therapy of PD. METHODS: In the present study, the protective function of luteolin-7-O-glucoside (LUT-7G), a natural flavonoid, was investigated in 1-methyl-4-phenylpyridinium (MPP+) treated SH-SY5Y cells and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice. RESULTS: Pre-treatment of LUT-7G increased the viability and reduced the apoptosis of SH-SY5Y cells treated by MPP+. At molecular level, the Bcl-2/Bax ratio was increased, while the expression of cleaved caspase 3 was markedly lessened. Moreover, LUT-7G increased the expression of estrogen receptor (ER), ERα and ERß, and enhanced the activation of ERK1/2/STAT3/c-Fos that could be abolished by ER antagonists. Furthermore, in vivo experiment indicated that pre-treatment of LUT-7G improved the bradykinesia, and enhanced the muscle strength as well as the balancing capacity of mice treated with MPTP. And LUT-7G prevented the injury of TH positive cells in substantia nigra and increased TH positive nerve fibers in striatum. In addition, pre-treatment of LUT-7G also significantly diminished the MPTP-induced gliosis in substantia nigra. CONCLUSIONS: LUT-7G effectively protected dopaminergic neurons against MPP+ or MPTP-induced toxicity, probably by activating the ER-mediated signaling pathway. Our findings explore the therapeutic potential of LUT-7G for PD therapy.

Asunto(s)

Neuronas Dopaminérgicas/efectos de los fármacos , Flavonas/farmacología , Glucósidos/farmacología , Intoxicación por MPTP/prevención & control , Fármacos Neuroprotectores/farmacología , Receptores de Estrógenos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Línea Celular , Antagonistas de Estrógenos/farmacología , Humanos , Hipocinesia/etiología , Hipocinesia/prevención & control , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Intoxicación por MPTP/patología , Intoxicación por MPTP/psicología , Masculino , Ratones , Ratones Endogámicos C57BL , Fuerza Muscular/efectos de los fármacos , Factor de Transcripción STAT3/efectos de los fármacos , Sustancia Negra/patología

RESUMEN

Olive leaves have become a promising source of phenolic compounds and flavonoids with high added value. Phenolic compounds and flavonoids are important sources of antioxidants and bioactives, and one of the processes used to effectively produce them is extraction via solvents, using aqueous ethanol solutions. To obtain the highest extraction yield per kg of biomass, olive leaves were extracted using a conventional technique (dynamic maceration) and an emerging technology, such as pressurized liquid extraction. Studies of the factors that influence these processes were performed: temperature, leaf moisture content, solvent/solid, and aqueous ethanol concentration were optimized using the central composite and Box-Behnken experiment designs. Pressurized liquid extraction resulted in more efficient oleuropein and luteolin-7-O-glucoside extraction than dynamic maceration. The operational conditions for maximizing the recovery of phenolic compounds and flavonoids and antioxidant capacity were determined to be 190 °C, leaf moisture content of 5%, and aqueous ethanol concentration of 80%.

Asunto(s)

Flavonas/química , Glucósidos/química , Iridoides/química , Olea/química , Antioxidantes/química , Cromatografía Líquida de Alta Presión , Flavonas/aislamiento & purificación , Flavonoides , Glucósidos/aislamiento & purificación , Glucósidos Iridoides , Iridoides/aislamiento & purificación , Olea/metabolismo , Fenoles/química , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Solventes/química , Temperatura

RESUMEN

Dietary chrysanthemum flower and wolfberry alone or together are widely consumed as a health beverage on a daily basis for centuries. The study aims to evaluate combinative effects of flower heads of Chrysanthemum morifolium cv. Hangju (C) and Lycium barbarum fruit (wolfberry, W) served as tea on chemical compounds, antioxidant and anti-inflammatory activities in RAW 264.7 macrophages. Eight phenolics were mainly detected in chrysanthemum flowers, whereas polysaccharides were dominant in wolfberry. The infusion of five combinations showed significantly antioxidant activities positively associated with the chrysanthemum flower content in chemical methods (ORAC and FRAP). However, the cellular-based CAA assay exhibited the highest antioxidant activities of the infusion at C:W = 1:1, indicating a synergistic interaction (CI = 0.11, P < .01). Additionally, the anti-inflammatory effect of infusion, specifically at a combination of C:W = 1:1, was observed by reducing the LPS-induced nitric oxide production, and inhibiting the expression of iNOS, TNF-α, IL-1ß, and IL-6 mRNA (P < .05). The infusion prepared at a C:W = 1:1 was found to inactivate MAPKs (ERK and JNK) and NF-κB. The antioxidant and anti-inflammatory mechanisms might be attributed to acacetin-7-O-rutinoside, luteolin-7-O-glucoside and chlorogenic acid from chrysanthemum flower, and wolfberry polysaccharide via multiple inflammatory pathways.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Chrysanthemum , Flores , Frutas , Lycium , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Chrysanthemum/química , Citocinas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Flores/química , Frutas/química , Mediadores de Inflamación/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lycium/química , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7

RESUMEN

Compositional variation was examined across 13 microgreens species/subspecies representing Brassicaceae, Chenopodiaceae, Lamiaceae, Malvaceae and Apiaceae, grown in controlled environment. Macro-mineral concentrations were determined by ion chromatography, chlorophyll and ascorbate concentrations, and hydrophilic/lipophilic antioxidant potentials by spectrophotometry, and major carotenoids by HPLC-DAD. Nitrate hyper-accumulators and wide genotypic differences in Na, K and S concentrations were identified. Antioxidant capacity was highest in brassicaceous microgreens and significant genotypic variation was demonstrated in chlorophyll and carotenoid concentrations. High phenolic content was confirmed in Lamiaceae microgreens, with significant varietal differences, and alternative phenolics-rich microgreens from the Apiaceae were identified. Twenty-eight phenolic compounds were variably detected and quantitated through Orbitrap LC-MS/MS with flavonol glycosides, flavones and flavone glycosides, and hydroxycinnamic acids representing 67.6, 24.8 and 7.6% of the mean total phenolic content across species, respectively. The obtained information is critical for selecting new species/varieties of microgreens that may satisfy demand for both taste and health.

Asunto(s)

Ambiente Controlado , Calidad de los Alimentos , Variación Genética , Genotipo , Valor Nutritivo , Fitoquímicos/análisis , Verduras/química , Verduras/genética , Verduras/crecimiento & desarrollo