luteolin-7-glucoside and Disease-Models--Animal

Reduning injection (RDN), a popular traditional Chinese medicine, formulated by three herbs (i.e., Artemisia carvifolia Buch.-Ham. ex Roxb., Lonicera japonica Thunb., and Gardenia jasminoides J. Ellis), has been widely used to treat upper respiratory infectious diseases in China.. To investigate the protective effect of RDN on both lipopolysaccharides (LPS)- and cecal ligation and puncture (CLP)-induced septic mice. To identify the potentially effective constituent, and to determine its protective effect and underlying mechanism in vivo and in vitro.. Male C57BL/6 mice were used to establish septic model by tail intravenous injection of 4 mg/kg LPS or CLP surgery. After modeling, mice were administered by tail intravenous injection of RDN in the dose of 16 or 8 mL/kg/day. The mortality, histopathology, plasma levels of inflammatory cytokines were evaluated respectively. In addition, we screened the potentially effective substances of RDN against sepsis by detecting the nitric oxide (NO) production in LPS-stimulated Raw 264.7 cells and verified the effect of luteoloside in CLP-induced septic mice subsequently. Finally, the underlying mechanisms of RDN and luteoloside were investigated in the inflammatory model in vitro.. Administration of RDN significantly reduced the mortality and increased the survival rate in both LPS- and CLP-induced septic mice. Meanwhile, RDN reduced the release of inflammatory cytokines accompanied by alleviating the organs damage of lung, liver, and kidney in CLP-induced septic mice. Moreover, several components from Gardenia jasminoides J. Ellis extract (ZZ) or Lonicera japonica Thunb and Artemisia carvifolia Buch.-Ham. ex Roxb extract (JQ) as well as the constituents of luteoloside, quercetin, and caffeic acid were screened out to have obvious anti-inflammatory activity, which may be the potentially effective substances of RDN against sepsis. We further verified the protective role of luteoloside in CLP-induced septic mice. In addition, RDN and luteoloside significantly inhibited both the secretion and translocation of mobility group box (HMGB)1, and HMGB1-mediated activation of TLR4/NF-κB/MAPKs signaling pathways.. RDN and its effective constituent luteoloside exhibited a significant protective effect against sepsis, which were potential candidate drugs for treatment of sepsis. The mechanism of antisepsis partly was related to inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways. The results provide an evidence base for the follow-up clinical application of RDN in treatment of sepsis.

Topics: Animals; Anti-Infective Agents, Local; Cecum; Disease Models, Animal; Drugs, Chinese Herbal; Glucosides; HMGB1 Protein; Injections; Lipopolysaccharides; Luteolin; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Myeloid Differentiation Factor 88; NF-kappa B p50 Subunit; Nitric Oxide; Protective Agents; RAW 264.7 Cells; Sepsis; Signal Transduction; Toll-Like Receptor 4

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Cynaroside (CYN) is the predominant derivative of luteolin in aerial parts of Bidens tripartita which has been used in folk medicine as a diaphoretic, diuretic, antiseptic and anti-inflammatory agent. In our study, alginate (ALG), which is an anionic polymer with bioadhesive properties, was used as a CYN carrier, and multiple hydrogel formulations were created. Additionally, the present study evaluated the in vivo anti-inflammatory and anti-allergic activities of all preparations.. Novel gel formulations as topical carriers for CYN obtained from B. tripartita were developed and characterized. The bioadhesive properties of the designed preparations were also evaluated in an ex vivo model using the skin of hairless mice. In vitro CYN release from all formulations was examined and analysed by HPLC. Histopathological evaluation of mouse skin sections stained with H&E after carrageenan and oxazolone administration was also carried out. In addition, the influence of CYN on cell proliferation was examined by the PCNA staining method.. The results showed that 10 % CYN inhibited the release of anti-inflammatory mediators, and both tested concentrations, which included 5 % and 10 % (2 mg and 20 mg CYN per site, respectively), reduced oxazolone-induced ear swelling. Histopathological examination of the samples revealed a marked reduction in paw skin and ear tissue inflammation and in inflammatory infiltrates. The influence of CYN on cell proliferation was examined by the PCNA staining method, and the staining and distribution of PCNA-immunoreactive (PCNA-IR) cells were observed. After the application of the 5 % and 10 % hydrogels, the investigated samples showed decreased nuclear immunoreactivity to PCNA, which was similar to that of the control. Moreover, after application of the placebo formulation, fewer PCNA-IR cells were also observed.. The obtained data suggest that the topical application of CYN significantly reduces the number of T cells, mast cells and histiocytes in mouse skin with inflammation or atopic dermatitis.

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Disease Models, Animal; Drug Compounding; Drug Liberation; Edema; Glucosides; Hydrogels; Luteolin; Male; Mice, Inbred C57BL; Oxazolone; Proliferating Cell Nuclear Antigen

Luteoloside, a flavonoid compound, has been reported to have anti-inflammatory, anti-oxidative, antibacterial, antiviral, anticancer, and cardioprotective effects, among others, but its neuroprotective effects have rarely been studied. The purpose of this study was to investigate the protective effect of luteoloside on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of luteoloside on cerebral ischemia-reperfusion (I/R). Male Sprague-Dawley rats were randomly divided into six groups: sham, MCAO, luteoloside (20 mg/kg, 40 mg/kg, 80 mg/kg) and nimodipine (4 mg/kg). The results showed that luteoloside alleviated neurologic deficits and cerebral edema as well as improved cerebral infarction and histopathological changes in MCAO rats. Luteoloside significantly inhibited I/R-induced neuroinflammation, as demonstrated by reduced levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the brain tissues of MCAO rats. Furthermore, our results demonstrated that luteoloside significantly suppressed the activation of nuclear factor-kappa B (NF-κB) signaling, upregulated the protein expression of peroxisome proliferator activated receptor gamma (PPARγ) and increased NF-E2-related factor (Nrf2) nuclear accumulation in MCAO rats. Collectively, our findings suggested that luteoloside played a crucial neuroprotective role by inhibiting NF-κB signaling in focal cerebral ischemia in rats. Furthermore, PPARγ and Nrf2 were also important for the anti-inflammatory effect of luteoloside. In addition, our data suggested that luteoloside might be an effective treatment for cerebral ischemia and other neurological disorders.

Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Cells, Cultured; Cyclooxygenase 2; Disease Models, Animal; Glucosides; Humans; Infarction, Middle Cerebral Artery; Interleukin-1beta; Luteolin; Male; Neurogenic Inflammation; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; PPAR gamma; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Disease Models, Animal; Flavones; Gene Expression Regulation; Glucosides; Humans; Humulus; Magnetic Resonance Spectroscopy; Mice; Monoamine Oxidase; Motor Activity; Oxidopamine; Parkinson Disease, Secondary; Plant Extracts; Tandem Mass Spectrometry

Bone destruction or osteolysis marked by excessive osteoclastic bone resorption is a very common medical condition. Identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for prevention and treatment of osteolytic conditions such as periprosthetic joint infection and periprosthetic loosening. Luteoloside, a flavonoid, is a natural bioactive compound with anti-inflammation and anti-tumor properties. However, the effect of Luteoloside on inflammation-induced osteolysis is unknown. Here, we found that Luteoloside exhibited a strong inhibitory effect on lipopolysaccharide (LPS)-induced osteolysis in vivo. In addition, Luteoloside suppressed RANKL-induced osteoclast differentiation and abrogated bone resorption in a dose-dependent manner. Further, we found that the anti-osteoclastic and anti-resorptive actions of Luteoloside are mediated via blocking NFATc1 activity and the attenuation of RANKL-mediated Ca

Topics: Animals; Anti-Inflammatory Agents; Calcium Signaling; Disease Models, Animal; Dose-Response Relationship, Drug; Durapatite; Glucosides; Lipopolysaccharides; Luteolin; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteolysis; RANK Ligand; RAW 264.7 Cells; Skull; Time Factors

Context Phillyrea latifolia L. (Oleaceae), commonly found in the Mediterranean region in Turkey, is used as medicinal teas for weight loss and hyperglycaemia in folk medicine. Objective The study investigated the possible effects of P. latifolia leaves aqueous extract's on weight loss and biochemical-histological changes in the rats fed a high-energy diet (HED), also isolated and determined the main phenolic compounds. Materials and methods Twenty-four male Wistar albino rats were divided into four equal groups such as the HED group fed a HED, the PLE group given only the extract of P. latifolia leaves (220 mg/kg), the HED + PLE group administrated with the extract of leaves (220 mg/kg) after being fed with HED and a control group fed with standard pellet diet. Results PLE administration caused a remarkable decrement of body weight in the HED + PLE group (p < 0.05). PLE showed an improved effect on structural integrity and decreased leukocyte infiltration in liver and small intestinal tissues. The blood glucose (117.3 mmol/L), leptin (5.6 ng/mL), total cholesterol (61.8 mg/dL) and LDL (9.3 mmol/L) levels were significantly increased in the HED group. PLE administration in the HED group decreased these levels. The levels of HDL (26.8 mmol/L) in the HED + PLE group were higher than both control and HED groups. Chemical composition was investigated and luteolin 7-O-glucoside and chlorogenic acid were determined for the first time in Turkish sample from the EtOAc extract of leaves. Discussion and conclusion Phillyrea latifolia leaves may have beneficial effects on obesity related cellular problems and may become a good source of antidiabetic medication.

Topics: Animals; Anti-Obesity Agents; Biomarkers; Blood Glucose; Chlorogenic Acid; Diet, High-Fat; Disease Models, Animal; Energy Intake; Glucosides; Hypoglycemic Agents; Intestine, Small; Lipids; Liver; Luteolin; Male; Obesity; Oleaceae; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats, Wistar; Time Factors; Weight Loss

The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis.

Topics: Acanthosis Nigricans; Aminoquinolines; Animals; Cell Differentiation; Cell Nucleus; Cell Proliferation; Cells, Cultured; Cellular Senescence; Disease Models, Animal; Glucosides; Humans; Imiquimod; Immunohistochemistry; Inflammation; Interleukin-22; Interleukins; Keratinocytes; Lipids; Luteolin; Mice, Inbred C57BL; Oxidation-Reduction; Phenotype; Protein Transport; Psoriasis; Signal Transduction; STAT3 Transcription Factor

Renal fibrosis characterized by accumulation of extracellular matrix protein results in chronic renal diseases including diabetic nephropathy. Transforming growth factor β1 (TGF-β1) signaling pathway plays a key role in mediating renal fibrosis. Hence, agents that antagonize TGF-β signaling could be candidate for kidney disease therapy.. We established renal fibrosis model both in vitro with fibroblast cells treated with rhTGF-β1 and streptozocin(STZ)-induced diabetic nephropathy rats model in vivo and evaluated the effect of the aqueous extract of Lycopus lucidus Turcz, the blood-circulation-promoting Chinese herb, on diabetic nephropathy and investigated the mechanism of action.. We found that Lycopus suppressed rhTGF-β1-induced Smad2 and ERK1/2 activation, down-regulated the expression of TGF-βRI, TGF-βRII, Smad4 and Smad7 in SV40 MES13 cells without inhibiting cell viability. In vivo, lycopus inhibited Smad2 phosphorylation, reduced mRNA level of TGF-β1, ameliorated expansion of the mesangial area in glomerular tissue and reduced the levels of Scr and BUN of serum and total-SOD (superoxide dismutase) activity in STZ-induced diabetic rats.. Lycopus is a novel inhibitor of renal fibrosis by blocking TGF-β signaling pathway and possess a protective effect on renal damage of STZ-induced diabetic nephropathy in rats.

Topics: Animals; Caffeic Acids; Cell Line; Cinnamates; Depsides; Diabetic Nephropathies; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Glucosides; Humans; Luteolin; Lycopus; Male; Mice; Phosphorylation; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Rosmarinic Acid; Signal Transduction; Streptozocin; Transforming Growth Factor beta1

Previously, we reported that an ethanol extract of Ailanthus altissima has antiinflammatory activity in an ovalbumin (OVA)-sensitized murine asthmatic model. To determine the biological compounds from this plant, luteolin-7-O-glucoside (L7G) was isolated and its antiasthmatic activity was evaluated in an in vivo murine asthmatic model. L7G (10 to 100 mg/kg, per os (p.o.)) reduced the amount of eosinophil infiltration in bronchoalveolar lavage (BAL) fluid in a dose-dependent manner. In comparison, dexamethasone (5 mg/kg, p.o.), which was used as a positive control, also strongly inhibited the number of infiltrating eosinophils. L7G inhibited both the prostaglandin E(2) (PGE(2)) and serum immunoglobulin E level in BAL fluid in a dose-dependent manner. In addition, L7G inhibited the transcript profiles of interleukin (IL)-4, IL-5, and IL-13 mRNA expression levels in the murine asthma model, as determined using reverse transcription-polymerase chain reaction (RT-PCR). These results suggest that the antiasthmatic activity of L7G in OVA-induced lung inflammation may occur in part via the downregulation of T helper 2 cytokine transcripts as well as the inhibition of PGE(2) production.

Topics: Ailanthus; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Cytokines; Dinoprostone; Disease Models, Animal; Down-Regulation; Female; Glucosides; Luteolin; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

Leaf extracts of Buddleja globosa (Buddlejaceae) are used in Chilean folk medicine for wound healing. The anti-inflammatory (topic and per os), analgesic (per os) effects and the antioxidant activity of Buddleja globosa were for the first time reported by us.. Assess the antinociceptive activity of the methanol sequential and global extracts using complementary chemical and thermal models of pain, characterize pharmacologically the antinociception induced, evaluate seasonal influence to support Buddleja globosa medicinal use.. Global methanol, sequential methanol and ethanol (leaves collected in autumn and summer) extracts were evaluated for oral and topic analgesia in tail flick, formalin and writhing models, verbascoside and 7-O-luteolin glucoside were assayed in tail flick and writhing. Ibuprofen was used as reference. For characterization of induced antinociception, naltrexone, naltrindole, tropisetron, nor-binaltorphimine, prazosin, yohimbine, atropine, and N-nitro-l-arginine methyl ester were used as antagonists and inhibitors drugs.. Seasonal influence was observed since autumn extract resulted less active. Extracts showed a dose-dependent antinociceptive activity in all assays, the highest effects were obtained for the formalin and writhing test. Verbascoside was more active than ibuprofen in the writhing test (67.6% and 50.0% at equimolar doses) and showed similar effects in the tail flick (topic and oral) near 25% at equivalent doses - ED25 or EC25 - to ibuprofen. Luteolin 7-O-glucoside was slightly more active in the tail flick test and nearly half active than verbascoside in the writhing assay. Effectiveness was higher for the sequential than for global alcoholic extracts, and can be increased by selective blocking of opioid receptors. Global methanol extract seems modulated only by naltrexone.. Analgesic effect of Buddleja globosa is here demonstrated validating its use in traditional medicine. Season influence is important to be considered.

Topics: Administration, Cutaneous; Administration, Oral; Analgesics; Animals; Buddleja; Chile; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Ibuprofen; Luteolin; Male; Medicine, Traditional; Mice; Pain; Pain Measurement; Phenols; Plant Extracts; Plant Leaves; Seasons