BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism.

BACKGROUND: Helicobacter pylori (H. pylori) is the main pathogen that causes a variety of upper digestive diseases. The drug resistance rate of H. pylori is increasingly higher, and the eradication rate is increasingly lower. The antimicrobial resistance of H. pylori is an urgent global problem. It has been confirmed that Banxia Xiexin decoction (BXXXT) demonstrates the effects of treating gastrointestinal diseases, inhibiting H. pylori and protecting gastric mucosa. The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H. pylori. AIM: To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H. pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT. METHODS: The aqueous extract of BXXXT was gained by water decocting method. The inhibitory effect of the aqueous extract on H. pylori was detected by dilution in vitro; drug-resistant H. pylori cells were used to build an acute gastritis model in vivo. Thereafter, the model mice were treated with the aqueous extract of BXXXT. The amount of H. pylori colonization, the repair of gastric mucosal damage, changes of inflammatory factors, apoptosis, etc., were assessed. In terms of mechanism exploration, the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry; the immune function of peripheral blood cells such as CD3+ T and CD4+ T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry; the H. pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected. Differently expressed genes were screened and verification was performed thereon with knockout expression. RESULTS: The minimum inhibitory concentration of BXXXT aqueous extract against H. pylori was 256-512 µg/mL. A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did; the BXXXT aqueous extract have at least 11 ingredients inhibiting H. pylori, including berberine, quercetin, baicalin, luteolin, gallic acid, rosmarinic acid, aloe emodin, etc., of which berberine, aloe emodin, luteolin and gallic acid have a synergistic effect; BXXXT aqueous extract was found to stimulate the expressions of CD3+ T and CD4+ T and increase the number of CD4+ T/CD8+ T in gastritis mice; the detection of transcriptome and proteome, quantitative polymerase chain reaction, Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes, and CagA, VacA, etc. CONCLUSION: BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H. pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine, emodin and luteolin, the main components of the extract; the extract could activate the immune function and enhance bactericidal effects; BXXXT aqueous extract, with main targets of BXXXT aqueous extract related to urease, virulence factors, etc., could reduce the urease and virulence of H. pylori, weaken its colonization, and reduce its inflammatory damage to the gastric mucosa.

Diet Supplementation of Luteolin before Fatty Liver Formation Improves Hepatic Steatosis in Obese Mice by Inhibiting Visceral Adipose Tissue Lipolysis.

SCOPE: Serotonin (5-HT)-induced visceral adipocyte lipolysis is essential for the development of obesity-related complications. Diet supplementation of luteolin prevents high-fat diet (HFD)-fed mice against obesity and associated fatty liver. However, independent of the body weight loss, whether dietary luteolin can substantially reduce hepatic steatosis remains unclear. METHODS AND RESULTS: In differentiated 3T3-L1 cells, 5-HT treatment promotes adipocyte lipolysis, while luteolin significantly inhibits 5-HT-induced lipolysis, Ca2+ -PKG cascade, and SIRT1/FoxO1/AMPKα signaling through binding to 5-HT receptor HTR2B. Further, 5-week-old mice are fed with an HFD for 16 weeks. At the 6th, 8th, or 10th weeks of HFD feeding, some mice are switched to a luteolin-containing HFD, respectively. In all HFD-fed mice, body weight gain and body component are unaffected by dietary luteolin. However, diet supplementation of luteolin at the 6th or 8th, rather than at the 10th weeks, alleviates hepatic steatosis. Meanwhile, dietary luteolin reduces epididymal adipose tissue (EAT) lipolysis, and represses the level of lipolytic enzyme, the expression of Htr2b, and the activation of PKG and SIRT1/FoxO1/AMPKα signaling in EAT. CONCLUSIONS: Diet supplementation of luteolin before the formation of fatty liver protects HFD-fed mice against ectopic lipid deposition in liver by inhibiting visceral adipocyte lipolysis.

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis.

Liver fibrosis is a global life-threatening disorder with no approved treatment. It leads to serious hepatic complications when progressive, such as cirrhosis and carcinoma. Luteolin (LUT) is a plant flavonoid possessing a promising therapeutic potential in various liver diseases particularly, liver fibrosis. It was reported to have potent anti-inflammatory and antioxidant properties. It also suppresses the proliferation of activated hepatic stellate cells (HSC) and induces their apoptosis. However, its poor aqueous solubility and exposure to metabolism hinder its clinical use. Mesenchymal stem cells (MSCs)-derived exosomes, nano-sized extracellular vesicles, have recently emerged as natural biocompatible drug delivery vehicles permitting efficient drug delivery. Accordingly, the present study aimed for the first time to investigate the potential of bone marrow MSCs-derived exosomes to improve LUTs antifibrotic effectiveness. LUT-loaded exosomes (LUT-Ex) were successfully developed, optimized and subjected to both in vitro and in vivo characterization. The elaborated LUT-Ex presented good colloidal properties (size; 150 nm, PDI; 0.3 and ζ-potential; -28 mV), typical vesicular shape, reasonable drug entrapment efficiency (40%) with sustained drug release over 72 h. Additionally, the cellular uptake study of coumarin-6-loaded exosomes in HEP-G2 revealed a significant enhancement in their uptake by 78.4% versus free coumarin-6 solution (p ≤ 0.001). Following a single intraperitoneal injection, LUT-Ex revealed a superior antifibrotic activity compared with either LUT-suspension or blank exosomes as evidenced by the results of biochemical and histopathological evaluation. In conclusion, the elaborated LUT-Ex could be addressed as a promising nanocarrier for effective treatment of liver fibrosis.

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro.

Background: Diarrheal diseases caused by protozoa have a great impact on human health around the world. Giardia lamblia is one of the most common flagellates in the intestinal tract. Factors such as adverse effects to first-line drugs or the appearance of drug-resistant strains, make it necessary to identify new treatment alternatives. Agroindustry waste, like pomegranate peel, are a source of phenolic compounds, which possess antiparasitic activities. In vivo studies demonstrated antigiardiasic potential by reducing cyst shedding and protecting intestinal cells; however, they did not identify the compounds or elucidate any mechanism of action in the parasite. The objective of this study is to identify potential molecular targets and to test the in vitro effects of polyphenols from Punica granatum on Giardia lamblia. Methods: The in vitro antigiardial potential of polyphenolic extract from pomegranate peel (Punica granatum L.) obtained using microwave-ultrasound methodology was evaluated on Giardia lamblia trophozoites. Extract phytochemical identification was performed by HPLC/MS analysis. The effect of polyphenolic extract on growth and adhesion capacity was determined by parasite kinetics; morphological damage was evaluated by SEM, alteration on α-tubulin expression and distribution were analyzed by western blot and immunofluorescence, respectively. Results: The pomegranate peel extract showed the presence of ellagitannins (punicalin and punicalagin, galloyl-dihexahydroxydiphenoyl-hexoside), flavones (luteolin), and ellagic acid, that caused an inhibitory effect on growth and adhesion capacity, particularly on cells treated with 200 µg/mL, where growth inhibition of 74.36%, trophozoite adherence inhibition of 46.8% and IC50 of 179 µg/mL at 48 h were demonstrated. The most important findings were that the extract alters α-tubulin expression and distribution in Giardia trophozoites in a concentration-independent manner. Also, an increase in α-tubulin expression at 200 µg/mL was observed in western blot and diffuse or incomplete immunolabeling pattern, especially in ventral disk. In addition, the extract caused elongation, disturbance of normal shape, irregularities in the membrane, and flagella abnormalities. Discussion: The pomegranate peel extract affects Giardia trophozoites in vitro. The damage is related to the cytoskeleton, due to expression and distribution alterations in α-tubulin, particularly in the ventral disk, a primordial structure for adhesion and pathogenesis. Microtubule impairment could explain morphological changes, and inhibition of adhesion capacity and growth. Besides, this is the first report that suggests that ellagic acid, punicalin, punicalagin and luteolin could be interactioning with the rich-tubulin cytoskeleton of Giardia. Further investigations are needed in order to elucidate the mechanisms of action of the isolated compounds and propose a potential drug alternative for the giardiasis treatment.

Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics.

Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological properties including antimalarial and antiviral. However, the underlying mechanism of the active compounds against SARS-CoV-2 remains unknown. Results in the present work have been interpreted from the view point of computational methods including molecular dynamics, free energy methods, and metadynamics to establish the related mechanism of action. Among the constituents of T. riparia studied, luteolin inhibited viral cell entry and was thermodynamically stable. The title compound exhibit residence time and unbinding kinetics of 68.86 ms and 0.014 /ms, respectively. The findings suggest that luteolin could be potent blocker of SARS-CoV-2 cell entry. The study shades lights towards identification of bioactive constituents from T. riparia against COVID-19, and thus bioassay can be carried out to further validate such observations.

Comparative biotransformation of luteolin and apigenin from the flower extract and the stem-and-leaf extract of Dendranthema morifolium Ramat. Tzvel. in rats.

BACKGROUND: The flower of Dendranthema morifolium Ramat Tzvel has been widely used as a nutritional health supplement worldwide. However, most of the studies have focused on the flower and the rest of the plant was neglected. Our hypothesis is that similar flavonoids may be present at different parts of D. morifolium, and the flavonoids may undergo a similar biotransformation pathway within the body. To investigate this hypothesis, an in vivo pharmacokinetic experimental model was developed to explore the comparative biotransformation of luteolin and apigenin after administration of D. morifolium extracts (10 g kg-1 , p.o.) in freely moving rats. Because luteolin and apigenin mainly underwent phase II metabolism, the metabolic enzymes of ß-glucuronidase/sulfatase or ß-glucuronidase were used to hydrolyze the plasma sample, depending on the biotransformation pathway involved. RESULTS: The results revealed that luteolin and apigenin mainly went through glucuronide and sulfate conjugations, respectively, in both the extract of flowers and the stem-and-leaf group. In addition, the area under the concentration curve (AUClast ) of luteolin glucuronides and sulfates in the group administered the stem-and-leaf extract was approximately 4.6 times higher than that of the flower extract group. The dominant products of biotransformation for apigenin were sulfates. CONCLUSION: These findings support our hypothesis that not only the flower parts of D. morifolium, but also the stem-and-leaf parts contain rich flavones, including glycosides and aglycone, and they undergo similar biotransformation pathways. © 2021 Society of Chemical Industry.

Physiological and biochemical responses of green and red perilla to LED-based light.

BACKGROUND: Light-emitting diodes (LEDs) are widely used in closed-type plant production systems to improve biomass and accumulate bioactive compounds in plants. Perilla has been commonly used as herbal medicine because of its health-promoting effects. This study aimed to investigate the physiological and biochemical responses of green and red perilla under various visible-light spectra. RESULTS: Results showed that red (R) LEDs improved fresh weights of shoots and roots, plant height, internode length, node number and leaf area, as well as photosynthetic rate of green and red perilla plants compared to blue (B) LEDs and RB combined LEDs. Meanwhile, B resulted in higher stomatal conductance, transpiration rate and Fv/Fm compared to R. Supplementation of green (G) and far-red (FR) did not enhance perilla growth. Reduction or absence of B decreased leaf thickness, adaxial and abaxial epidermis, and palisade and spongy mesophyll. Total phenolic content, antioxidant capacity, rosmarinic acid content and caffeic acid content of green perilla were higher under R, R8B2 and RGB + FR, while greater values were obtained in red perilla under R. Accumulation of perillaldehyde, luteolin and apigenin presented different trends from those of rosmarinic and caffeic acids in both cultivars. CONCLUSIONS: Growth and accumulation of bioactive compounds in green perilla were greater than in red perilla under similar light quality, and R LEDs or a higher R ratio in combination treatments were suitable for cultivating high-quality green and red perilla plants in closed-type plant factories. © 2020 Society of Chemical Industry.

Computational screening of antagonists against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking.

In the current spread of novel coronavirus (SARS-CoV-2), antiviral drug discovery is of great importance. AutoDock Vina was used to screen potential drugs by molecular docking with the structural protein and non-structural protein sites of new coronavirus. Ribavirin, a common antiviral drug, remdesivir, chloroquine and luteolin were studied. Honeysuckle is generally believed to have antiviral effects in traditional Chinese medicine. In this study, luteolin (the main flavonoid in honeysuckle) was found to bind with a high affinity to the same sites of the main protease of SARS-CoV-2 as the control molecule. Chloroquine has been proved clinically effective and can bind to the main protease; this may be the antiviral mechanism of this drug. The study was restricted to molecular docking without validation by molecular dynamics simulations. Interactions with the main protease may play a key role in fighting against viruses. Luteolin is a potential antiviral molecule worthy of attention.

[Effects of different temperature stress on cell membrane permeability,active oxygen metabolism and accumulation of effective substances in Lonicera japonicea].

The study is aimed to explore the effects of stress at different temperatures( 35,45,55 ℃) on membrane permeability,active oxygen metabolism and accumulation of effective substances in Lonicera japonica,and provide theoretical basis for reducing deterioration and revealing browning mechanism during postharvest processing of L. japonica. The cell membrane permeability( relative conductivity,MDA content),active oxygen metabolism( SOD,POD,PPO,CAT activity) and the accumulation of effective substances( chlorogenic acid,luteolin,neochlorogenic acid,cryptochlorogenic acid,3,5-dicaffeoylquinic acid,3,4-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid) of L. japonica were all studied by constant temperature drying method,and the results were analyzed by the SPSS 17. 0 statistical software. The results showed that MDA content in L. japonica was increased by 151. 14% at 35 ℃,SOD,POD,PPO and CAT activity were 29. 73%,42. 86%,105. 02% and 10. 74% higher than at 45 ℃,respectively. The order of effective substance content in L. japonica was 35 ℃ >45 ℃ >55 ℃. The changes of membrane permeability,activity of active oxygen metabolizing enzyme and accumulation of active components were significantly affected by different temperature stress. The indexes showed that physiological and active oxygen metabolizing enzyme activity of L. japonica was the highest under 35 ℃ stress,chlorogenic acid and luteolin were effectively accumulated,which provides basic data for solving browning problem in the postharvest processing of L. japonica.

Use of greenhouse-covering films with tailored UV-B transmission dose for growing 'medicines' through plants: rocket salad case.

BACKGROUND: The effects of ultraviolet B (UV-B) radiation on plants are well known and have recently attracted a great deal of attention due to the production of large quantities of secondary metabolites, which are very beneficial for human health. Recent studies have demonstrated the possibility of exploiting UV-B radiation to induce metabolic changes in fruit, vegetables, and herbs. The role of UV-B rays in inducing secondary plant metabolites is enhanced by new plastic films, which, as a result of their optical properties, permit the necessary dosage of UV-B to be transmitted into the greenhouse to stimulate such metabolites without altering the harvest. RESULTS: The main goal of the present paper is to demonstrate that, by using a greenhouse plastic film with appropriate transmittance of UV-B for rocket salad cultivation, it is possible to increase the nutraceutical elements in comparison with the same species grown in absence of such radiation. Tests compared nutritional elements extracted from rocket salad grown under greenhouses covered with several plastic films differing in UV-B transmittance. We found that rocket salad grown under plastic with 27% UV-B transmittance exhibited very high luteolin and quercetin content in comparison with rocket salad cultivated under film blocking UV-B radiation. CONCLUSIONS: Our experimental results confirm the possibility of exploiting UV-B radiation in the correct amounts by appropriate greenhouse plastic covers, to produce natural 'medicines' using the plants and to satisfy increasing consumer demand for natural health-promoting food products. © 2019 Society of Chemical Industry.

Can luteolin be a therapeutic molecule for both colon cancer and diabetes?

Diabetes and colon cancer are the leading cause of mortality worldwide. According to World Health Organization, the number of patients with diabetes and cancer is going to be elevated by 50% in 2020. However, several flavonoids have been known to be useful in reducing the chance of cancer/diabetes but the hunt of a single biomolecule that can act as therapeutic and preventive molecules for future epidemic continues. In this review, we aim to perform an illustration of all researches done that target molecular signaling using luteolin in cancer/diabetes and predicted target protein using PharmMapper. The search confirms that luteolin can be a remedial molecule for both cancer and diabetes via acting on variety of signaling pathway. Furthermore, we also intend to illustrate/compare the predicted and verified molecular modes of action of luteolin. Fluorescence in situ hybridization analysis confirms the expression of CCND1 in colon cancer while immunofluorescence analysis confirms the CDK4 in diabetes. Finally, an effort has been made to map docking of marker protein-luteolin at a particular site using docking software. This review gives a holistic overview about luteolin as a therapeutic molecule for cancer/diabetes via acting on multiple signaling cascade such as p53, Wnt, eNOS, iNOS, SOD and MMP9, with especial emphasis on the cyclin-CDK pathway. Altogether, the review concludes that luteolin can be a molecule for the therapy of both cancer and diabetes by acting on broad signaling pathway.

Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat.

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

Experimental Probing and Molecular Dynamics Simulation of the Molecular Recognition of DNA Duplexes by the Flavonoid Luteolin.

Luteolin (C15H10O6) is an important flavonoid found in many fruits, plants, medicinal herbs, and vegetables exhibiting many pharmacological properties. The anticancer, antitumor, antioxidant, and anti-inflammatory activities of luteolin have been reported. The pharmacological action of small molecules is dependent upon its interaction with biomacromolecules. The interactions of small molecules with DNA play a major role in the transcription and translation process. In this work, we explored the energetic profile of DNA-luteolin interaction by isothermal titration calorimetry (ITC). The effect of temperature and salt concentration on DNA binding was examined by UV-Vis method. The mode of interaction was further probed by UV melting temperature analysis and differential scanning calorimetry. An atomic level insight on the recognition of luteolin with DNA was achieved by employing molecular dynamics (MD) simulation on luteolin in complex with AT- and GC-rich DNA sequences. AMBER force field proves to be appropriate in providing an understanding on the binding mode and specificity of luteolin with duplex DNA. MD results suggest a minor groove binding of luteolin with DNA and the binding free energy obtained is in agreement with the experimental results.

Identification of Phenolic Compounds from Seed Coats of Differently Colored European Varieties of Pea (Pisum sativum L.) and Characterization of Their Antioxidant and In Vitro Anticancer Activities.

To date little has been done on identification of major phenolic compounds responsible for anticancer and antioxidant properties of pea (Pisum sativum L.) seed coat extracts. In the present study, phenolic profile of the seed coat extracts from 10 differently colored European varieties has been determined using ultrahigh-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometer technique. Extracts of dark colored varieties with high total phenolic content (up to 46.56 mg GAE/g) exhibited strong antioxidant activities (measured by 2,2-diphenyl-1-picrylhydrazyl or DPPH assay, and ferric ion reducing and ferrous ion chelating capacity assays) which could be attributed to presence of gallic acid, epigallocatechin, naringenin, and apigenin. The aqueous extracts of dark colored varieties exert concentration-dependent cytotoxic effects on all tested malignant cell lines (human colon adenocarcinoma LS174, human breast carcinoma MDA-MB-453, human lung carcinoma A594, and myelogenous leukemia K562). Correlation analysis revealed that intensities of cytotoxic activity of the extracts strongly correlated with contents of epigallocatechin and luteolin. Cell cycle analysis on LS174 cells in the presence of caspase-3 inhibitor points out that extracts may activate other cell death modalities besides caspase-3-dependent apoptosis. The study provides evidence that seed coat extracts of dark colored pea varieties might be used as potential cancer-chemopreventive and complementary agents in cancer therapy.

Absorption and Metabolism of Luteolin and Its Glycosides from the Extract of Chrysanthemum morifolium Flowers in Rats and Caco-2 Cells.

To elucidate the bioavailability of luteolin and its glycosides in Chrysanthemum morifolium flowers, the absorption and metabolism of luteolin from them was investigated in rats and Caco-2 cells using HPLC and LC-MS. After oral administration of C. morifolium extract (1.7 g/kg body weight (bw), equivalent to 22.8 and 58.3 µmol/kg bw of luteolin and luteolin-7-O-glucoside, respectively) to rats, luteolin and its glycosides were quickly absorbed and luteolin, luteolin monoglucoside, and luteolin monoglucuronide were detected in the plasma. Their levels were highest at 1 h after administration (0.76 ± 0.27 µM). These compounds were also detected in media on the basolateral side from Caco-2 cells treated with the C. morifolium extract. These results suggest that luteolin and luteolin monoglucoside are rapidly absorbed after administration of C. morifolium flower extract and that luteolin, luteolin monoglucoside, and luteolin monoglucuronide may circulate in humans.

Antibacterial behaviour of Vitex negundo extract assisted ZnO nanoparticles against pathogenic bacteria.

The biological routes are advantageous over the chemical and physical ones as unlike. These, the biological synthesis protocol occurs at ambient conditions, are cheap, non-toxic and eco-friendly. This research describes the synthesis of zinc oxide nanoparticles (ZnO NPs) using Vitex negundo plant extract with zinc nitrate hexahydrate as precursor. Biomolecules present in plant extract can be used to hydrolyze metal ions into metal oxide NPs in a single-step green synthesis. The hydrolyzing agents involved the various water soluble plant metabolites such as flavonoid, alkaloids, flavone, phenolic compounds, terpenoids and co-enzymes. Presence of isoorientin (flavone) in V. negundo plant extract is mainly responsible for the formation of ZnO NPs. The prepared ZnO NPs were calcinated at 450°C and were confirmed by XRD, FT-IR, UV-visible, SEM with EDX and DLS analysis. The biological application of antibacterial activity was done by gram positive and gram negative bacteria.

Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway.

Vascular inflammation plays a significant role in the pathogenesis of atherosclerosis. Luteolin, a naturally occurring flavonoid present in many medicinal plants and some commonly consumed fruits and vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of luteolin at physiological concentrations remain unclear. Here, we report that luteolin as low as 0.5 µM significantly inhibited tumor necrosis factor (TNF)-α-induced adhesion of monocytes to human EA.hy 926 endothelial cells, a key event in triggering vascular inflammation. Luteolin potently suppressed TNF-α-induced expression of the chemokine monocyte chemotactic protein-1 (MCP-1) and adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), key mediators involved in enhancing endothelial cell-monocyte interaction. Furthermore, luteolin inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, IκBα degradation, expression of IκB kinase ß and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that luteolin can inhibit inflammation by suppressing NF-κB signaling. In an animal study, C57BL/6 mice were fed a diet containing 0% or 0.6% luteolin for 3 weeks, and luteolin supplementation greatly suppressed TNF-α-induced increase in circulating levels of MCP-1/JE, CXCL1/KC and sICAM-1 in C57BL/6 mice. Consistently, dietary intake of luteolin significantly reduced TNF-α-stimulated adhesion of monocytes to aortic endothelial cells ex vivo. Histology shows that luteolin treatment prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization as shown by Verhoeff-Van Gieson staining. Immunohistochemistry studies further show that luteolin treatment also reduced VCAM-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, luteolin protects against TNF-α-induced vascular inflammation in both in vitro and in vivo models. This anti-inflammatory effect of luteolin may be mediated via inhibition of the NF-κB-mediated pathway.

Influence of olive leaf processing on the bioaccessibility of bioactive polyphenols.

Olive leaves are rich in bioactive compounds, which are beneficial for humans. The objective of this work was to assess the influence of processing conditions (drying and extraction) of olive leaves on the extract's bioaccessibility. Thus, extracts obtained from dried olive leaves (hot air drying at 70 and 120 °C or freeze-drying) by means of conventional or ultrasound-assisted extraction were subjected to in vitro digestion. Antioxidant capacity, total phenolic content, and HPLC-DAD/MS/MS analysis were carried out during digestion. The dehydration treatment used for the olive leaves did not have a meaningful influence on bioaccessibility. The digestion process significantly (p<0.05) affected the composition of the extracts. Oleuropein and verbascoside were quite resistant to gastric digestion but were largely degraded in the intestinal phase. Nevertheless, luteolin-7-O-glucoside was the most stable polyphenol during the in vitro simulation (43% bioaccessibility). Therefore, this compound may be taken into consideration in further studies that focus on the bioactivity of olive leaf extracts.

Luteolin alleviates alcoholic liver disease induced by chronic and binge ethanol feeding in mice.

Ethanol consumption can lead to hepatic steatosis that contributes to late-stage liver diseases such as cirrhosis and hepatocellular carcinoma. In this study, we investigated the potential protective effect of a flavonoid, luteolin, on ethanol-induced fatty liver development and liver injury. Six-wk-old male C57BL/6 mice were divided into 3 groups: a control group; a group exposed to alcohol by using a chronic and binge ethanol feeding protocol (EtOH); and a group that was administered daily 50 mg/kg of luteolin in addition to ethanol exposure (EtOH + Lut). A chronic and binge ethanol feeding protocol was used, including chronic ethanol consumption (1%, 2%, and 4% for 3 d, and 5% for 9 d) and a binge (30% ethanol) on the last day. Compared with the control group, the EtOH group had a significant elevation in serum concentrations of alanine aminotransferase (ALT) (561%), triglyceride (TG) (47%), and LDL cholesterol (95%), together with lipid accumulation in the liver. Compared with the EtOH group, the EtOH + Lut group had significant reductions in serum concentrations of ALT (43%), TG (22%), LDL cholesterol (52%), and lipid accumulation in the liver. Ethanol elevated liver expression of lipogenic genes including sterol regulatory element-binding protein 1c (Srebp1c) (560%), fatty acid synthase (Fasn) (190%), acetyl-CoA carboxylase (Acc) (48%), and stearoyl-CoA desaturase 1 (Scd1) (286%). Luteolin reduced ethanol-induced expression of these genes in the liver: Srebp1c (79%), Fasn (80%), Acc (60%), and Scd1 (89%). In cultured hepatocytes, luteolin prevented alcohol-induced lipid accumulation and increase in the expression of lipogenic genes. The transcriptional activity of the master regulator of lipid synthesis, sterol regulatory element-binding protein (SREBP), was enhanced by ethanol treatment (160%) and reduced by luteolin administration (67%). In addition, ethanol-induced reduction of AMP-activated protein kinase and SREBP-1c phosphorylation was abrogated by luteolin. Collectively, our study indicates that luteolin is effective in ameliorating ethanol-induced hepatic steatosis and injury.

Exploiting genes and functional diversity of chlorogenic acid and luteolin biosyntheses in Lonicera japonica and their substitutes.

Chlorogenic acids (CGAs) and luteolin are active compounds in Lonicera japonica, a plant of high medicinal value in traditional Chinese medicine. This study provides a comprehensive overview of gene families involved in chlorogenic acid and luteolin biosynthesis in L. japonica, as well as its substitutes Lonicera hypoglauca and Lonicera macranthoides. The gene sequence feature and gene expression patterns in various tissues and buds of the species were characterized. Bioinformatics analysis revealed that 14 chlorogenic acid and luteolin biosynthesis-related genes were identified from the L. japonica transcriptome assembly. Phylogenetic analyses suggested that the function of individual gene could be differentiation and induce active compound diversity. Their orthologous genes were also recognized in L. hypoglauca and L. macranthoides genomic datasets, except for LHCHS1 and LMC4H2. The expression patterns of these genes are different in the tissues of L. japonica, L. hypoglauca and L. macranthoides. Results also showed that CGAs were controlled in the first step of biosynthesis, whereas both steps controlled luteolin in the bud of L. japonica. The expression of LJFNS2 exhibited positive correlation with luteolin levels in L. japonica. This study provides significant information for understanding the functional diversity of gene families involved in chlorogenic acid and the luteolin biosynthesis, active compound diversity of L. japonica and its substitutes, and the different usages of the three species.