1-1-diphenyl-2-picrylhydrazyl and Inflammation

Sixteen chebulic acid derivatives, including nine new (1-9) and seven known (10-16) ones, were isolated from an ethanol extract of the branches and leaves of Balakata baccata. The structures of the new compounds were elucidated by their UV, IR, HRESIMS, NMR, electronic circular dichroism (ECD) and single-crystal X-ray diffraction data. The effects of all the isolates on antineuroinflammatory and antioxidant activities were evaluated. Compared with the positive control minocycline (IC

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Benzopyrans; Biphenyl Compounds; Cell Line; Dose-Response Relationship, Drug; Inflammation; Lipopolysaccharides; Mice; Molecular Structure; Nitric Oxide; Picrates; Plant Leaves; Sapium; Structure-Activity Relationship

Humans rely on plants as a necessitous source of their food, energy, cosmetics and medicines, as medicinal plants are rich source of new therapeutically active compounds from decades. Current study was designed to separate and identify active constituents of Erythrina suberosa bark extract using phytochemical screening and gas chromatography and mass spectroscopy, respectively and evaluated their therapeutic activities. E. suberosa bark extract contained saponins, glycosides, alkaloids, tannins, terpenoids, phenols and 44 active compounds identified by phytochemical and gas chromatography and mass spectroscopic analysis. Therapeutic potentials of E. suberosa bark extract was evaluated by such as cytotoxicity, anti-inflammatory and antioxidant assay. Surprisingly, bark extract shows the concentration dependent cytotoxicity against human fibroblast malignant melanoma-144 cell lines and remarkably inhibited (15.18(plusmn;1.13%, at 400mg/ml) growth of cancer cells after 24 hours treatment. In addition, the E. suberosa bark extract also exhibited anti-inflammatory effect at higher doses (400mg/kg) and moderate antioxidant activity is also noticed through (2, 2-diphenyl-1-picrylhydrazyl radical) assay. These findings indicate that E. suberosa bark extract exhibited prominent anticancer and anti-inflammatory activities and might be serve as a potent therapeutic agent in future.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Carrageenan; Cell Line, Tumor; Cell Proliferation; Chemical Fractionation; Disease Models, Animal; Erythrina; Gas Chromatography-Mass Spectrometry; Humans; Inflammation; Neoplasms; Phytochemicals; Picrates; Plant Bark; Plant Extracts; Rats

Diarrhea is a multifactorial gastrointestinal disorder responsible for about 5 million deaths annually. The chemical composition, the antioxidant activity of Crataegus azarolus berries aqueous extract (CABAE) as well as its protective effects against castor oil-induced diarrhea, oxidative stress, and inflammation in rat were studied.. Sixty male rats were used and divided into six groups of ten animals in each: Control (C), castor oil (CO), CO+various doses of CABAE (100, 200, and 400 mg/kg b.w., p.o.), and CO+loperamide (LOP, 10 mg/kg b.w., p.o.).. The CABAE showed relatively high levels of total polyphenols, flavonoids, and tannins. The LC-HRESIMS technique allowed the identification of 5 phenolic compounds and the major component is quinic acid. In vivo studies showed that CABAE protected against castor oil-induced diarrhea and intestinal fluid accumulation. The CABAE counteracted castor oil-induced lipoperoxidation, preserved GSH and thiol groups levels, and prevented the depletion of antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The CABAE administration also protected against castor oil-induced inflammatory markers (ALP and CRP) increase. More importantly, castor oil induced an increase of intracellular mediators, such as hydrogen peroxide, free iron, and calcium, while CABAE pretreatment significantly reversed them to near control levels.. The Crataegus azarolus berries aqueous extract significantly protected against diarrhea due in part to its antioxidant and anti-inflammatory properties.

Topics: Animals; Antidiarrheals; Antioxidants; Biphenyl Compounds; Castor Oil; Cathartics; Crataegus; Diarrhea; Flavonoids; Fruit; Inflammation; Loperamide; Male; Oxidative Stress; Phenols; Picrates; Plant Extracts; Quinic Acid; Rats; Rats, Wistar; Tannins

Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-

Topics: Albumins; Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Catechols; Chemical and Drug Induced Liver Injury, Chronic; Diethylnitrosamine; Fatty Alcohols; Free Radical Scavengers; Free Radicals; Glutathione; Hydrogen Peroxide; In Vitro Techniques; Inflammation; Lipid Peroxidation; Liver; Male; Mitochondria; Oxidative Stress; Picrates; Rats; Zingiber officinale

As a mild cationic antibacterial agent, hydroxypropyltrimethyl ammonium chloride chitosan (HACC) could kill gram-positive bacteria and gram-positive drug-resistant bacteria without cytotoxicity. Nevertheless, it was not effective against gram-negative bacteria. Herein, protocatechuic acid (PA) with broad-spectrum antibacterial properties and pharmacological activities was grafted on HACC. PA-g-HACC showed favourable antioxidant capacity and anti-inflammatory properties. Most importantly, the results of antibacterial assay indicated that the antibacterial rates of all PA-g-HACC groups against Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) were above 92 %, and the antibacterial rate of PA-g-HACC against E. coli was increased with the amount of grafted PA. Furthermore, the cytocompatibility of PA-g-HACC was improved by appropriate grafting ratio of PA, while excessive grafted PA can lead to toxicity. We believe that PA-g-HACC in optimum grafting ratio of PA with favorable antibacterial properties, pharmacological activities and cytocompatibility will be potential antibacterial agent for treating infections.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Biofilms; Biphenyl Compounds; Chemistry, Pharmaceutical; Chitosan; Drug Design; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Hydroxybenzoates; Inflammation; Magnetic Resonance Spectroscopy; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; NIH 3T3 Cells; Picrates; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; X-Ray Diffraction

White tip silver needle, a slightly fermented white tea, is abundant in flavonoids, and it has great significance in terms of D-galactose/lipopolysaccharide-induced aging in mice.. We analyzed the antioxidant capacity of white tip silver needle flavonoids (WTSNF) in vitro, assessed the effects of WTSNF on organ indexes, pathological changes, liver function indexes, biochemical indicators, molecular biological indicators, and genes related to oxidation and inflammation.. Ultra-high performance liquid chromatography-tandem mass spectrometry results showed that WTSNF contained baicalin, kaempferol, kaempferide, quercetin, isorhamnetin, lespenephryl, and rutin. WTSNF showed strong scavenging ability for both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) free radicals. Pathological analysis results showed that WTSNF reduced liver, kidney, and lung damage in mice with induced aging. In the serum and liver tissue, WTSNF effectively increased the antioxidant-related levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and total antioxidant capacity and reduced the levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde and nitric oxide. WTSNF also reduced the inflammation-related levels of interleukin-6, interleukin-1 beta, tumor necrosis factor alpha (TNFα), and interferon gamma (IFN-γ) and increased the levels of interleukin-10 and interleukin-12. Furthermore, WTSNF upregulated the mRNA expression levels of cupro-zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, interleukin-10, neuronal nitric oxide synthase, endothelial nitric oxide synthase, nuclear factor erythroid 2-related factor, heme oxygenase 1, NAD(P)H dehydrogenase [quinone] 1, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α), and thioredoxin, while it downregulated the mRNA expression levels of interleukin-6, interleukin-18, interleukin-1 beta, TNFα, IFN-γ, inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB).. WTSNF is a high-quality natural product with antioxidative and anti-inflammatory properties that can inhibits D-galactose/lipopolysaccharide-induced aging in mice.

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Benzothiazoles; Biphenyl Compounds; Cytokines; Flavonoids; Galactose; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred Strains; Picrates; RNA, Messenger; Sulfonic Acids

The genus Rumex (Polygonaceae) is distributed worldwide and the different species belonging to it are used in traditional medicine. The present study aimed at the evaluation of the phytochemical profile and the biochemical properties of methanolic extracts from different parts (roots, stems, and leaves) of Rumex roseus, a wild local Tunisian plant traditionally used as food.  The phytochemical analysis on the extracts was performed using standard colorimetric procedures, HPLC-DAD, and HPLC-DAD-ESI-MS; then, several in vitro cell-free assays have been used to estimate their antioxidant/free radical scavenging capability (TAC-PM, DPPH, TEAC, FRAP, ORAC, SOD-like activity, and HOCl-induced albumin degradation). Additionally, anti-inflammatory effect of these extracts was evaluated in an in vitro model of acute intestinal inflammation in differentiated Caco-2 cells. The results showed that the methanolic extracts from stems and, especially, leaves contain substantial amounts of flavones (apigenin and luteolin, together with their derivatives), while the extract from roots is characterized by the presence of tannins and quinic acid derivatives. All the extracts appeared endowed with excellent antioxidant/free radical scavenging properties. In particular, the extract from roots was characterized by a remarkable activity, probably due to its different and peculiar polyphenolic composition. Furthermore, both Rumex roseus roots and stems extracts demonstrated an anti-inflammatory effect in intestinal epithelial cells, reducing TNF-α-induced gene expression of IL-6 and IL-8. In conclusion, R. roseus methanolic extracts have shown to be potential sources of bioactive compounds to be used in the prevention and treatment of pathologies related to oxidative stress and inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biphenyl Compounds; Caco-2 Cells; Cattle; Cells, Cultured; Humans; Inflammation; Methanol; Mice; NIH 3T3 Cells; Oxidative Stress; Phytochemicals; Picrates; Rumex; Serum Albumin, Bovine

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cinnamates; Depsides; Flavanones; Free Radical Scavengers; Homeostasis; Humans; Inflammation; Larva; MCF-7 Cells; Oxidation-Reduction; Picrates; Resveratrol; Rosmarinic Acid; Wasps; Wound Healing

Topics: Anti-Inflammatory Agents; Biphenyl Compounds; Cell Survival; Chromatography, High Pressure Liquid; Drug Evaluation, Preclinical; Fruit; Glucose; Humans; Inflammation; Keratinocytes; MAP Kinase Signaling System; Myrtaceae; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; NFATC Transcription Factors; Oxidative Stress; Picrates; Plant Extracts; Reactive Oxygen Species; Signal Transduction

The frequency, complexity and morbidity of neurodegenerative diseases make them a great challenge for nowadays medicine. Most of the treatments currently used for Parkinson's disease - the second most prevalent - are only symptomatic. Therefore, it is urgent to develop drugs that are able to act simultaneously on different targets, being able to stop neuronal death and promote the recovery of neuronal populations already affected. In this work, we studied the activity of a series of hybrid molecules, which combine the structure of both coumarin and an alkynylamine group inspired on rasagiline, as MAO inhibitors, antioxidants and neuroprotective agents. Half of the studied hybrids turned out to be selective monoamine oxidase B (hMAO-B) inhibitors in the low micro/nanomolar range, demonstrating that positions 3 (compounds 1-3) and 7 (compounds 8 and 10) of the coumarin scaffold are the most suitable for the incorporation of the alkynylamine chain. All the studied compounds proved to be capable of neutralizing free radicals (DPPH). Finally, the 4-(but-2-yn-1-ylamino)coumarin (5) showed neuroprotective effects on glial cells and the 4-methyl-7-(pent-2-yn-1-ylamino)coumarin (8) inhibited intraneuronal ROS production as well.

Topics: Animals; Antioxidants; Biphenyl Compounds; Cells, Cultured; Coumarins; Female; Humans; Hydrogen Peroxide; Indans; Inflammation; Lipopolysaccharides; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurons; Neuroprotective Agents; Oxidative Stress; Picrates; Rats; Rats, Wistar

Topics: A549 Cells; Animals; Antioxidants; Apoptosis; Basidiomycota; Biphenyl Compounds; Bleomycin; Cell Nucleus; Cell Survival; Cytoplasm; Fungal Polysaccharides; Humans; Hydrogen Peroxide; Inflammation; Male; Mice; Oxidative Stress; Picrates; Pulmonary Fibrosis; Reactive Oxygen Species; Signal Transduction

Reactive oxygen species (ROSs), acting as functionalized molecules in intracellular enzyme reactions and intercellular communication of immune response, play vital roles in biological metabolism. However, the inevitably excessive ROS-induced oxidative stress is harmful for organ tissue, causing unexpected local anaphylaxis or inflammation. Here, we demonstrate carbon dots (CDs), made of citric acid and glutathione via one-step hydrothermal method, as a highly efficient intracellular ROS scavenger for alleviating the lipopolysaccharide (LPS)-induced inflammation in macrophage. These CDs have broad-spectrum antioxidant properties and the total antioxidant activity exceeds 51.6% higher than that of the precursor, namely, glutathione, in the same mass concentration. Moreover, their antioxidative performance in macrophage inflammation induced by LPS was investigated, and it was found that CDs can efficiently remove up to 98% of intracellular ROS, notably inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and decrease the expression level of inflammatory factor IL-12. Our results suggested that CDs can serve as a highly efficient intracellular ROS scavenger and could be employed to cope with oxidative stress-induced diseases.

Topics: Animals; Antioxidants; Biphenyl Compounds; Carbon; Cell Survival; Cells, Cultured; Citric Acid; Glutathione; Inflammation; Lipopolysaccharides; Macrophages; Mice; Microscopy, Confocal; Molecular Conformation; Optical Imaging; Particle Size; Picrates; Quantum Dots; Reactive Oxygen Species; Surface Properties

Etlingera elatior (Jack) R.M. Smith rhizome, which has been traditionally used to reduce stomach discomfort, was reported to possess anti-inflammatory activity, however, there is a lack of such a study on the flower.. To investigate the anti-inflammatory activity of the E. elatior flower extract on gastric ulceration-induced Wistar rats. The Wistar rats were divided into 6 groups. Group 1 was the normal control, group 2 was the negative control (Arabic gum suspension 2%), group 3 was the positive control (quercetin), group 4-6 were treated with E. elatior flower extract dose of 500, 1000 and 2000 mg kg-1 of b.wt., respectively. The rats were conditioned to gastric ulceration. The stomach weight, microscopic and macroscopic evaluation of gastric mucosal damage was examined. Subsequently, the nuclear factor-kappaB-p65 (NF-kappaB-p65) expression in the fundus was Western-blotted by employing β-actin and GAPDH as the loading controls.. Etlingera elatior flower extract dose of 1000 mg kg-1 b.wt., reduces the ulceration index and the infiltration of inflammatory cells. Western blot analysis showed inhibition of NF-kappaB-p65 expression by E. elatior flower extract dose of 1000 mg kg-1 of b.wt.. Etlingera elatior flower might possess anti-inflammatory activity by downregulating the expression of NF-kappaB-p65 in the fundus of gastric ulceration-induced Wistar rats.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Flowers; Gastric Mucosa; Inflammation; Inhibitory Concentration 50; Male; Phenol; Picrates; Plant Extracts; Quercetin; Rats; Rats, Wistar; Rhizome; Stomach; Stomach Ulcer; Transcription Factor RelA; Zingiberaceae

Vascular stent interventional therapy, as a regular and effective therapy, has been widely used to treat coronary artery diseases. However, adverse events occur frequently after stent intervention, especially restenosis and late stent thrombosis. The targeted implanting site will suffer from severe atherosclerosis, which is considered as a chronic inflammatory disease. Meanwhile, with the over-expanding use of endovascular mechanical intervention, vascular injury has become an increasingly common issue. Lesions and newly induced vascular injury result in inflammatory and oxidative stress; meanwhile, activated macrophages and granulocytes generate high levels of reactive oxygen species (ROS), contributing to endothelial dysfunction and neointima hyperplasia. Therefore, attenuating oxidative stress and reducing ROS generation in the inflammatory response represent reasonable strategies to inhibit intimal hyperplasia and restenosis. Herein, we have developed a multifunctional surface for the MgZnYNd alloy with tannic acid (TA) coating, and the pH dependence of the coating deposition is also demonstrated. The phenolic hydroxyl groups on the coatings endow the modified surface with excellent antioxidant functions. We found that the coating can be recycled, and the scavenging activity hardly weakened within five cycles. Also, the TA coating has a promising strong antioxidant activity as it shows a radical scavenging activity over 80% in long term. Moreover, the TA coating possesses platelet-repellent capability. No significant inflammatory response was observed for the TA modified sample in the rat subcutaneous implantation test. Combining these performances, we envision that the vascular stent modified with TA coating can have great potential in various applications by virtue of its simplicity and effectiveness.

Topics: Alloys; Animals; Antioxidants; Biphenyl Compounds; Blood Platelets; Cell Proliferation; Coronary Restenosis; Fluorides; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen-Ion Concentration; Inflammation; Neodymium; Oxidative Stress; Picrates; Platelet Adhesiveness; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stents; Tannins; Thrombosis; Zinc

Schiff bases (SBs) are chemical compounds displaying a significant pharmacological potential. They are able to modulate the activity of many enzymes involved in metabolism and are found among antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative drugs. A new thiazolyl-triazole SB was obtained and characterized by elemental and spectral analysis. The antibacterial and antifungal ability of the SB was evaluated against Gram-positive and Gram-negative bacteria and against three

Topics: Anti-Bacterial Agents; Antifungal Agents; Antioxidants; Bacteria; Biomarkers; Biphenyl Compounds; Cell Survival; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipid Peroxidation; Malondialdehyde; Microbial Sensitivity Tests; Oxidative Stress; Picrates; Schiff Bases; Thiazoles; Tumor Necrosis Factor-alpha

Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. It has been shown that the intercellular reactive oxygen species (ROS) generation activated by lipopolysaccharide involved in the nuclear factor kappa B (NF-κB) activation and pathogenesis of NEC. Here, we report that an antioxidant peptide from tuna backbone protein (APTBP) reduces the inflammatory cytokines transcription and release. APTBP directly scavenges the free radical through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) assay. In addition, APTBP reduces the intracellular ROS level, exhibiting an antioxidant activity within cells. Remarkably, gavage with APTBP attenuates the phenotype of NEC in the mice model. Mechanically, the NF-κB activation, together with the expression of inflammatory cytokines are decreased significantly when intracellular ROS are eliminated by APTBP. Therefore, our findings demonstrated that an antioxidant peptide, APTBP, ameliorates inflammation in NEC through attenuating ROS-NF-κB axis.

Topics: Animals; Animals, Newborn; Biphenyl Compounds; Cyclic N-Oxides; Cytokines; Disease Models, Animal; Enterocolitis, Necrotizing; Humans; Imidazoles; Inflammation; Intestinal Mucosa; Lipopolysaccharides; Mice; NF-kappa B; Peptides; Picrates; Rats; Reactive Oxygen Species; Tuna

Ketoprofen belongs to one of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione-type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti-inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen-antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic-OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants (IIa-h) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen-antioxidant through the glycolic acid spacer (-CH

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Biphenyl Compounds; Humans; Hydrolysis; Inflammation; Ketoprofen; Kinetics; Molecular Structure; Pain; Picrates; Rats; Stomach Ulcer

Inflammation is a consequence of an array of biological reactions that occur in response to pain sensation, local injury, and cell damage. A large number of studies have demonstrated that quercetin and other flavonoids show anti-inflammatory effects; thus, in the present work, we evaluated a triazine-phenol derivative (TP derivative) compound as a possible drug candidate with anti-inflammatory activity. This compound was studied as a possible anti-inflammatory drug using synthesis and characterization by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and mass spectrometry (MS). The derivative of melamine was evaluated for its antioxidant activity and exhibited good DPPH and FRAP antioxidant activity. Additionally, we evaluated the putative effect of the molecule on the COX-2 enzyme through molecular dynamic simulation (MDS), and the result suggested that the TP derivative is a potential anti-inflammatory agent that can interact with the COX-2 enzyme because of the high number of protein-ligand interactions observed with MDS. Finally, the study of theoretical physicochemical properties, the observation of low toxicity (hemolysis assay), and the evaluation of oral bioavailability of the TP derivative showed that it is a possible anti-inflammatory drug candidate.

Topics: Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Computer Simulation; Cyclooxygenase 2; Erythrocytes; Flavonoids; Hemolysis; In Vitro Techniques; Inflammation; Ligands; Molecular Docking Simulation; Phenol; Picrates; Quercetin; Triazines

Juniperus communis L. represents a multi-purpose crop used in the pharmaceutical, food, and cosmetic industry. Several studies present the possible medicinal properties of different Juniperus taxa native to specific geographical area. The present study aims to evaluate the genoprotective, antioxidant, antifungal and anti-inflammatory potential of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills.. The prepared hydroethanolic extract of Juniperus communis L. was characterized by GC-MS, HPLC, UV-Vis spectrometry and phytochemical assays. The antioxidant potential was evaluated using the DPPH assay, the antifungal effect was studied on Aspergillus niger ATCC 15475 and Penicillium hirsutum ATCC 52323, while the genoprotective effect was evaluated using the Allium cepa assay. The anti-inflammatory effect was evaluated in two inflammation experimental models (dextran and kaolin) by plethysmometry. Male Wistar rats were treated by gavage with distilled water (negative control), the microemulsion (positive control), diclofenac sodium aqueous solution (reference) and microemulsions containing juniper extract (experimental group). The initial paw volume and the paw volumes at 1, 2, 3, 4, 5 and 24 h were measured.. Total terpenoids, phenolics and flavonoids were estimated to be 13.44 ± 0.14 mg linalool equivalent, 19.23 ± 1.32 mg gallic acid equivalent, and 5109.6 ± 21.47 mg rutin equivalent per 100 g of extract, respectively. GC-MS characterization of the juniper extract identified 57 volatile compounds in the sample, while the HPLC analysis revealed the presence of the selected compounds (α-pinene, chlorogenic acid, rutin, apigenin, quercitin). The antioxidant potential of the crude extract was found to be 81.63 ± 0.38% (measured by the DPPH method). The results of the antifungal activity assay (for Aspergillus niger and Penicillium hirsutum) were 21.6 mm, respectively 17.2 mm as inhibition zone. Test results demonstrated the genoprotective potential of J. communis undiluted extract, inhibiting the mitodepressive effect of ethanol. The anti-inflammatory action of the juniper extract, administered as microemulsion in acute-dextran model was increased when compared to kaolin subacute inflammation induced model.. The hydroalcoholic extract obtained from wild-growing Juniperus communis native to Romanian southern sub-Carpathian hills has genoprotective, antioxidant, antifungal and anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Antifungal Agents; Aspergillus niger; Biphenyl Compounds; Flavonoids; Inflammation; Juniperus; Male; Penicillium; Phenols; Picrates; Plant Extracts; Protective Agents; Rats; Rats, Wistar; Romania

Resveratrol is a natural polyphenol found mainly on red grapes and in red wine, pointed as an important anti-inflammatory/immunomodulatory molecule. However, its bioavailability problems have limited its use encouraging the search for new alternatives agents. Thus, in this study, we synthetize 12 resveratrol analogues (6 imines, 1 thioimine and 5 hydrazones) and investigated its cytotoxicity, antioxidant activity and in vitro anti-inflammatory/immunomodulatory properties. The most promising compounds were also evaluated in vivo. The results showed that imines presented less cytotoxicity, were more effective than resveratrol on DPPH scavenger and exhibited an anti-inflammatory profile. Among them, the imines with a radical in the para position, on the ring B, not engaged in an intramolecular hydrogen-interaction, showed more prominent anti-inflammatory activity modulating, in vivo, the edema formation, the inflammatory infiltration and cytokine levels. An immunomodulatory activity also was observed in these molecules. Thus, our results suggest that imines with these characteristics presents potential to control inflammatory disorders.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Antioxidants; Biological Availability; Biphenyl Compounds; Cell Proliferation; Cytokines; Down-Regulation; Imines; Inflammation; Inflammation Mediators; Lymphocytes; Major Histocompatibility Complex; Mice; Mice, Inbred C57BL; Peroxidase; Picrates; RAW 264.7 Cells; Resveratrol

Inflammation is a complex phenomenon that results as a healing response of organisms to different factors, exerting immune signaling, excessive free radical activity and tissue destruction. Lipoxygenases and their metabolites e.g., LTB₄, are associated with allergy, cell differentiation and carcinogenesis. Lipoxygenase 12/15 has been characterized as a mucosal-specific inhibitor of IgA and a contributor to the development of allergic sensitization and airway inflammation. Development of drugs that interfere with the formation or effects of these metabolites would be important for the treatment of various diseases like asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer and blood vessel disorders. In this study we extended our previous research synthesizing a series of multi-target cinnamic acids from the corresponding aldehydes with suitable 4-OH/Br substituted phenyl acetic acid by Knoevenagel condensation. The final products

Topics: Benzothiazoles; Biphenyl Compounds; Cinnamates; Hydroxyl Radical; Inflammation; Lipid Peroxidation; Lipoxygenase; Oxidative Stress; Picrates; Sulfonic Acids

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Benzothiazoles; Biphenyl Compounds; Edema; Hydroxides; Inflammation; Male; Methanol; Mice; Ononis; Phytotherapy; Picrates; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley; Skin; Sulfonic Acids; Wound Healing

SC-E1 is a novel herbal formula consisting of five oriental medicinal herbs used frequently in traditional herbal medicine for the treatment of inflammatory diseases in Korea. This study examined the effects of SC-E1 on lipopolysaccharide (LPS)-stimulated macrophages and the molecular mechanism involved.. The cytotoxic effect of the SC-E1 extract was evaluated in RAW 264.7 cells by MTT assay. The effects of SC-E1 on the free radical scavenging and generation of intracellular reactive oxygen species were measured using DPPH and DCFH-DA, respectively. The effects of SC-E1 on the production of pro-inflammatory cytokines, inflammatory mediators, and related products were determined by ELISA and western blotting. The molecular mechanism and the nuclear translocation of nuclear factor-kappa B (NF-κB) and NF-E2-related factor 2 (Nrf2) were examined by western blot analysis and immunocytochemistry.. SC-E1 exhibited strong anti-oxidant activity and inhibited LPS-induced NO secretion as well as iNOS expression and the production of pro-inflammatory cytokines, without affecting the cell viability. SC-E1 also suppressed the LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Moreover, SC-E1 induced heme oxygenase-1 (HO-1) expression via the nuclear translocation of Nrf2. The inhibitory effects of SC-E1 on the production of pro-inflammatory cytokines were abrogated by treatment with SnPP, an HO-1 inhibitor.. These results suggest that SC-E1 exerts its anti-oxidant and anti-inflammatory effects through the inhibition of NF-κB and MAPK as well as Nrf2-mediated HO-1 induction in macrophages. These findings provide evidences for SC-E1 to be considered as a new prescription for treating inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Cytokines; Fluoresceins; Gardenia; Glycyrrhiza; Heme Oxygenase-1; Inflammation; Lipopolysaccharides; Magnoliopsida; Medicine, Korean Traditional; Membrane Proteins; Mice; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Picrates; Plant Extracts; Platycodon; Pueraria; RAW 264.7 Cells; Signal Transduction

The diet supplementation with antioxidants-rich products is a way to protect people from free radical-induced diseases. In this study, we compare the anti-inflammatory/antioxidant activity of two compounds available as supplements: alpha lipoic acid (ALA) and ferulic acid (FA).. The free radical scavenging capacity of ALA and FA in the cell free system was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Anti-inflammatory activity of both compounds was determined, in vitro, on THP-1 derived macrophages model, both resting (not stimulated) and inflammatory (lipopolysaccharide- or tumor-necrosis factor α-stimulated).. We have found that FA exhibits much higher radical scavenging activity than ALA, in cell free system. The functional assays demonstrated that although both ALA and FA limited the reactive oxygen species (ROS) formation in the presence of inflammatory macrophages, the latter acid was significantly more effective. Only FA reduced the release of pro-inflammatory interleukin 1β and interleukin 6 by lipopolysaccharide-treated macrophages. Neither FA nor ALA affected the viability of macrophages.. Among those two compounds only FA has significant free radical scavenging activity in cell free system and acts as anti-inflammatory and antioxidant agent on macrophages. It can be assumed that application of FA in a diet can protect the host from the development and/or progression of inflammation.

Topics: Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Cell Line; Coumaric Acids; Free Radical Scavengers; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophages; Oxidants; Picrates; Reactive Oxygen Species; Thioctic Acid; Tumor Necrosis Factor-alpha

Inflammation activated by oxidative stress can cause various diseases, such as asthma, rheumatoid arthritis, cancer, diabetes, etc. Plant constituents with sesquiterpene lactones possess antioxidant and anti-inflammatory properties.. To determine the antioxidant and anti-inflammatory potential of isolated phytoconstituent from Cyathocline purpurea Buch-Ham ex D (CP). Don in laboratory animals. Furthermore, to understand the interactions involved in the binding of this compound to cyclooxygenase-2 (COX-2) via computational docking.. Phytoconstituent was isolated, purified and well characterized (using IR, NMR, and MS) from ethyl acetate fraction of CP methanolic extract. It was then evaluated for its in-vitro antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H. The presence of hydroxyl group in HGN provides a credential to its in-vivo anti-inflammatory and in-vitro antioxidant activities. Furthermore, the good binding affinity of HGN for the active site of COX-2 may open novel vistas in therapeutic option with natural antioxidants like Cyathocline purpurea to treat various inflammatory disorders.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Asteraceae; Biphenyl Compounds; Carrageenan; Cells, Cultured; Cyclooxygenase 2; Edema; Female; Humans; Hydrogen Peroxide; Inflammation; Male; Mice; Oxidative Stress; Phytotherapy; Picrates; Rats; Rats, Wistar; Sesquiterpenes, Guaiane

The effects of phytochemicals occurred in fractions and extracts of fruits of "Maqui-berry" (Aristotelia chilensis), on the expression of cyclooxygenase-2 (COX-2), inducible-nitric oxide synthases (iNOS) and the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-activated murine macrophage RAW-264 cells, as well as their antioxidant activities. The MeOH extract (A), acetone/methanol extract (B), fractions F3, F4, subfractions (SF4-SF6, SF7, SF8-SF10, SF11-SF15, SF16-SF20), quercetin, gallic acid, luteolin, myricetin, mixtures M1, M2 and M3 exhibited potent anti-inflammatory and antioxidant activities. The results indicated that anthocyanins, flavonoids and its mixtures suppressed the LPS induced production of nitric oxide (NO), through the down-regulation of iNOS and COX-2 protein expressions and showed a potent antioxidant activity against SOD, ABTS, TBARS, ORAC, FRAP and DCFH. The inhibition of enzymes and NO production by selected fractions and compounds was dose-dependent with significant effects seen at concentration as low as 1.0-50.0 (ppm) and 5.0-10.0 μM, for samples (extracts, fractions, subfractions and mixtures) and pure compounds, respectively. Thus, the phenolics (anthocyanins, flavonoids, and organic acids) as the fractions and mixtures may provide a potential therapeutic approach for inflammation associated disorders and therefore might be used as antagonizing agents to ameliorate the effects of oxidative stress.

Topics: Animals; Biphenyl Compounds; Brain; Cyclooxygenase 2; Elaeocarpaceae; Fruit; Inflammation; Iron; Lipid Peroxidation; Mice; Nitric Oxide Synthase Type II; Oxidation-Reduction; Oxygen Radical Absorbance Capacity; Picrates; Plant Extracts; Polyphenols; Rats; RAW 264.7 Cells; Thiobarbituric Acid Reactive Substances

Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine.. The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied.. Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400 mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated.. Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, β-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-β-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-β-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400 mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400 mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC50) value: 9.07 μg/ml).

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Behavior, Animal; Biphenyl Compounds; Butanols; Cajanus; Carrageenan; Cytokines; Disease Models, Animal; Egypt; Female; Gas Chromatography-Mass Spectrometry; Hexanes; Immunologic Factors; Inflammation; Inflammation Mediators; Lipid Peroxidation; Male; Mice; Nociceptive Pain; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Rats; Seeds; Solvents; Time Factors

Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Carrageenan; Cell Line; Chemotaxis, Leukocyte; Disease Models, Animal; Dose-Response Relationship, Drug; Hydrogen Peroxide; Inflammation; Lipopolysaccharides; Macrophages, Peritoneal; Male; Methanol; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Oxidative Stress; Phytotherapy; Picrates; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Rubus; Saponins; Skin; Solvents; Wound Healing; Wounds, Penetrating

The present study was designed to investigate the gastroprotective effect of xanthones 7-preniljacareubin (PJB), 1,3,5,6-tetrahydroxy xanthone (THX), 3-demethyl-2-geranyl-4-prenylbellidypholine (DGP) and 1,5,8-trihydroxy-4', 5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) isolated of branches from G. achachairu. Their structures were identified through the spectroscopic analysis in comparison with previously reported data. The xanthones were tested at dose of 10 mg/kg against ethanol 60%/HCl 0.3 N-induced gastric ulcer in female swiss mice. The xanthones PJB, THX, DGP and TDP exhibit gastroprotective effect after intraperitoneal treatment, but only the first two displayed anti-ulcer activity after oral administration. Both PJB and THX augmented the antioxidative capacity of tissue by an increase in glutathione levels, as well as were able to prevent an increase in myeloperoxidase activity and tumor necrosis factor level. On the other hand, only THX showed an in vitro free radical scavenger activity, and only PJB avoided mucus depletion on gastric mucosa, which was not associated with an increase in mucin production at glandular level. In addition, PJB and THX inhibited the in vitro H(+)K(+)-ATPase activity at similar range as omeprazole. Together, these results demonstrate the anti-ulcer efficacy of xanthones isolated from G. achachairu, which can contribute for future directions in the development of effective strategies to improve gastric diseases.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Biphenyl Compounds; Carbon-13 Magnetic Resonance Spectroscopy; Female; Free Radical Scavengers; Garcinia; Gastric Mucosa; Glutathione; H(+)-K(+)-Exchanging ATPase; Immunohistochemistry; Inflammation; Mice; Mucins; Peroxidase; Picrates; Protective Agents; Proton Magnetic Resonance Spectroscopy; Stomach Ulcer; Tumor Necrosis Factor-alpha; Xanthones

The fruit of Cyrtocarpa procera is used to treat stomach diseases by people living in San Rafael, Coxcatlan, Puebla. This work investigated the antibacterial, antioxidant, cytotoxic and anti-inflammatory activities of the fruit produced by this species.. Methanol extract was obtained by maceration. After obtaining the methanol extract (MeOH1), methanol subextract (MeOH2) and hexane (H) were obtained. The antibacterial activities of MeOH1, MeOH2 and H were evaluated through disc-diffusion. The quenching of free radicals was evaluated by decolorizing a methanolic DPPH solution. The cytotoxic activity of MeOH2 was evaluated by in vitro assay system of growth inhibition of human cervical carcinoma cell line (CasKi). The IL-1β and TNF-α were determined through ELISA in the supernatants of the macrophage cell line (RAW 264.7). The MeOH2 subextract was separated by column chromatography, seventy-three fractions were collected.. The Gram-positive and -negative bacteria examined were sensitive to MeOH1 and MeOH2; the MeOH2 was bactericidal toward Staphyloccocus aureus (MIC = 4 mg/mL) and Vibrio cholera (MIC = 4 mg/mL). The MeOH2 inhibited the DPPH radical (SC50 = 69.7 μg/mL), but a cytotoxicity assay revealed that the extract is not toxic according to the National Cancer Institute (LD50 = 22.03 μg/mL). The production of proinflammatory cytokines (IL- 1β and TNF- α) by LPS- stimulated macrophages was reduced after the treatments. The methanol extract contained various organic acids, such as citric acid, palmitic acid and α- linoleic acid.. The fruits of Cyrtocarpa procera are employed to treat ailments such as diarrhea, in this study were demonstrated some biological activities involved in a bacterial infection. This is the first research about of the medicinal properties of C. procera fruit.

Topics: Anacardiaceae; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Cell Line, Tumor; Diarrhea; Fruit; Humans; Infections; Inflammation; Interleukin-1beta; Lipopolysaccharides; Macrophages; Mice; Phytotherapy; Picrates; Plant Extracts; Staphylococcus aureus; Tumor Necrosis Factor-alpha; Vibrio cholerae

Microglial activation is known to cause inflammation resulting in neurotoxicity in several neurological diseases. N-((3,4-Dihydro-2H-benzo[h]chromene-2-yl)methyl)-4-methoxyaniline (BL-M), a chromene derivative, was originally synthesized with the perspective of inhibiting nuclear factor-kappa B (NF-κB), a key regulator of inflammation. The present study evaluated the antioxidant and anti-inflammatory potential of BL-M in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our results demonstrated that BL-M significantly inhibited the formation of 1,1-diphenyl-2-picrylhydrazyl radicals, as well as lipid peroxidation in rat brain homogenate in a concentration-dependent manner. In addition, it suppressed the generation of intracellular reactive oxygen species, and the levels of pro-inflammatory mediators including nitric oxide, tumor necrosis factor-α, and interleukin-6 in LPS-induced BV2 cells. Western blotting analyses revealed the inhibition of inhibitor of kappa B alpha (IκBα) phosphorylation and NF-κB translocation by BL-M in LPS-activated cells. Therefore, our study highlights marked antioxidant and anti-inflammatory activities of BL-M, and suggests that this compound may have a beneficial impact on various neurodegenerative diseases associated with inflammation.

Topics: Aniline Compounds; Animals; Anti-Inflammatory Agents; Antioxidants; Benzopyrans; Biphenyl Compounds; Cell Line; I-kappa B Proteins; Inflammation; Inflammation Mediators; Lipid Peroxidation; Lipopolysaccharides; Microglia; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Picrates; Rats; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Coumarins, also known as benzopyrones, are plant-derived products with several pharmacological properties, including antioxidant and anti-inflammatory activities. Based on the wide distribution of coumarin derivatives in plant-based foods and beverages in the human diet, our objective was to evaluate both the antioxidant and intestinal anti-inflammatory activities of six coumarin derivatives of plant origin (scopoletin, scoparone, fraxetin, 4-methyl-umbeliferone, esculin and daphnetin) to verify if potential intestinal anti-inflammatory activity was related to antioxidant properties.. Intestinal inflammation was induced by intracolonic instillation of TNBS in rats. The animals were treated with coumarins by oral route. The animals were killed 48 h after colitis induction. The colonic segments were obtained after laparotomy and macroscopic and biochemical parameters (determination of glutathione level and myeloperoxidase and alkaline phosphatase activities) were evaluated. The antioxidant properties of these coumarins were examined by lipid peroxidation and DPPH assays.. Treatment with esculin, scoparone and daphnetin produced the best protective effects. All coumarin derivatives showed antioxidant activity in the DPPH assay, while daphnetin and fraxetin also showed antioxidant activity by inhibiting lipid peroxidation. Coumarins, except 4-methyl-umbeliferone, also showed antioxidant activity through the counteraction of glutathione levels or through the inhibition of myeloperoxidase activity.. The intestinal anti-inflammatory activity of coumarin derivatives were related to their antioxidant properties, suggesting that consumption of coumarins and/or foods rich in coumarin derivatives, particularly daphnetin, esculin and scoparone, could prevent intestinal inflammatory disease.

Topics: Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Colitis; Colon; Coumarins; Esculin; Glutathione; Inflammation; Inflammatory Bowel Diseases; Lipid Peroxidation; Male; Oxidative Stress; Peroxidase; Phytotherapy; Picrates; Plant Extracts; Rats; Rats, Wistar; Umbelliferones

The cellular and molecular mechanisms by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remain active areas of research. We previously demonstrated that both the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress, contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically responsive, mechanically adaptive polymer implants based on poly(vinyl alcohol) (PVA), with the capability to also locally administer the antioxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and antioxidant release - leads to synergistic effects in vivo. Over the first 4weeks of the implantation, curcumin-releasing, mechanically adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat PVA controls. 12weeks post-implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically adaptive intracortical implants.

Topics: Animals; Antioxidants; Astrocytes; Biphenyl Compounds; Blood-Brain Barrier; Cell Count; Cellulose; Cerebral Cortex; Cicatrix; Curcumin; Glial Fibrillary Acidic Protein; HMGB1 Protein; Immunoglobulin G; Implants, Experimental; Inflammation; Macrophages; Male; Microglia; Nanoparticles; Neuraminidase; Neurons; Permeability; Picrates; Polyvinyl Alcohol; Rats; Urochordata; Wound Healing

In the present study, the pharmacological effects of 2,8-dihydroxy-1,6-dimethoxyxanthone from the bark of Haploclathra paniculata were investigated in mice using in vivo inflammation and nociception models. Acetic acid-induced writhing, paw licking induced by formalin, hot plate, and carrageenan-induced paw edema tests were used to investigate the anti-inflammatory and antinociceptive activities of the xanthone compound. Xanthone, at both doses, inhibited abdominal writhing and the formalin test. At a dose of 20 mg/kg, the time of reaction to the hot plate increased, and significant effects were observed after 30, 60 and 90 min of treatment. At doses of 10 and 20 mg/kg p.o., the 2,8-dihydroxy-1,6-dimethoxyxanthone significantly reduced paw edema at 3 h after the stimulus. The tests also showed no acute toxicity of the xanthone compound in mice. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability was also studied and confirmed the antioxidant activity of the xanthone. To propose the mechanism of action of anti-inflammatory activity of the xanthone, a molecular docking was performed using the isoenzymes cyclooxygenase 1 and 2 and the results indicate that the molecule is capable of inhibiting both the enzymes. Therefore, it can be concluded that 2,8-dihydroxy-1,6-dimethoxyxanthone from H. paniculata demonstrates analgesic, anti-inflammatory, and antioxidant activities.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Carrageenan; Clusiaceae; Cyclooxygenase 2 Inhibitors; Edema; Hot Temperature; Inflammation; Male; Pain; Pain Measurement; Phytotherapy; Picrates; Plant Bark; Plant Extracts; Prostaglandin-Endoperoxide Synthases; Rats, Wistar; Xanthones

Methanol extract subfractions of the edible white jelly mushroom (Tremella fuciformis), were assessed for the following antioxidant properties: ABTS(+) radical scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and inhibitory activity of human low-density lipoprotein (LDL) oxidation. Among the subfractions tested, the chloroform subfraction exhibited the strongest antioxidant activity, with the highest total phenolic content (66.31 μg CAE/mg extract) and flavonoids content (5.12 μg QE/mg extract). The ABTS(+) radical scavenging activity of the chloroform subfraction was 7.89 μmol trolox/mg extract, which was the highest among all subfractions. This subfraction also showed the highest DPPH radical scavenging activity and inhibitory activity of LDL oxidation. In addition, the chloroform subfraction demonstrated anti-inflammatory activity through inhibition of nitric oxide production and inducible nitric oxide synthase expression in RAW 264.7 cells. Major phenolic acids from the mushroom extract were identified as 4-hydroxybenzoic acid (323 mg/kg dry weight of mushroom), gentisic acid (174 mg/kg dry weight of mushroom), and 4-coumaric acid (30 mg/kg dry weight of mushroom).

Topics: Agaricales; Anti-Inflammatory Agents; Antioxidants; Basidiomycota; Benzothiazoles; Biological Products; Biphenyl Compounds; Cell Line; Coumaric Acids; Flavonoids; Gentisates; Humans; Inflammation; Lipoproteins, LDL; Nitric Oxide; Nitric Oxide Synthase Type II; Parabens; Phenols; Picrates; Propionates; Sulfonic Acids

The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20μg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Biphenyl Compounds; Carrageenan; Daphne; Dose-Response Relationship, Drug; Edema; Female; Flavonoids; Freund's Adjuvant; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; Nitric Oxide; Phytotherapy; Picrates; Plant Extracts; Rats

Based on the fact that Synadenium grantii is used in folk medicine for the treatment of peptic ulcers and inflammatory diseases, this work describes its chemical and pharmacological properties. Pharmacological investigation of the crude bark extract showed a high antioxidant activity over several scavenger systems, such as 2,2'-azino-bis (3-ethylenebenzothiazoline-6-sulfonic acid)• +, 1-diphenyl-2-picrylhydrazyl•, O2 • - , and HOCl, as well as an enzymatic system with human myeloperoxidase and an ex vivo hemolysis system. Furthermore, the oral administration of the crude bark extract was able to reduce carrageenan-induced rat paw edema as effectively as ibuprofen. These biological activities may be associated with the presence of flavonoids and terpenes, as revealed by HPLC and NMR analyses of the crude stem bark extract. The phytochemical investigations in this study resulted in the isolation of friedelin and 3β-friedelinol for the first time, while euphol and lanosterol were also isolated.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Benzothiazoles; Biphenyl Compounds; Carrageenan; Edema; Euphorbia; Female; Flavonoids; Humans; Inflammation; Lanosterol; Peroxidase; Phytotherapy; Picrates; Plant Bark; Plant Extracts; Plant Stems; Rats, Wistar; Sulfonic Acids; Triterpenes

The aim of this study was to investigate the antioxidant potential of ampelopsin (APS) by using various methods in vitro, as well as to determine effects of APS on LPS-induced oxidative stress in piglets. The results showed that APS exhibited excellent free radical scavenging by DPPH, ABTS, O2•-, H2O2 and ferric reducing antioxidant power. Ampelopsin also protected pig erythrocytes against AAPH-induced apoptosis and hemolysis, decreased total superoxide dismutase activity, and increased lipid peroxidation. Furthermore the results demonstrated that APS enhanced the total antioxidant capacity and decreased the malondialdehyde and protein carbonyl contents in LPS-treated piglets. The results of the present investigation suggest that APS possesses a strong antioxidant activity and alleviates LPS-induced oxidative stress, possibly due to its ability to prevent reactive oxygen species.

Topics: Amidines; Animals; Antioxidants; Apoptosis; Benzothiazoles; Biphenyl Compounds; Erythrocytes; Female; Flavonoids; Hemolysis; Hydrogen Peroxide; Inflammation; Injections, Intraperitoneal; Lipid Peroxidation; Lipopolysaccharides; Malondialdehyde; Oxidants; Oxidative Stress; Picrates; Protein Carbonylation; Sulfonic Acids; Superoxide Dismutase; Superoxides; Swine

A Saururus chinensis Baill (SC) has been used by Native Americans, early colonists and practitioners of Korean traditional medicine for treating several diseases including cancer, rheumatoid arthritis and edema. The objective of this study was to evaluate the effects of SC extract in lipopolysaccharide (LPS)-stimulated neuroinflammatory responses in BV-2 microglial cells.. The effects of SC on the LPS-induced neuroinflammatory responses in BV-2 microglial cells were assessed by Western blotting, RT-PCR and immunofluorescence labeling techniques. DPPH and alkyl radical scavenging assay was performed to evaluate the anti-oxidant effects. Comparisons between groups were analyzed using one-way analysis of variance followed by Dunnett's multiple comparisons test using GraphPad Prism V5.01 software.. Pre-treatment with SC extract (1, 5 and 10 μg/mL) significantly (p < 0.001 at 10 μg/mL) and concentration dependently inhibited LPS-induced production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) and suppressed the inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin (IL)-6 in BV-2 microglial cells (p < 0.001 at 10 μg/mL). Further, SC suppressed the nuclear factor-kappa B (NF-κB) activation by blocking the degradation of IκB-α. SC also exhibited profound anti-oxidant effects by scavenging 1, 1-diphenyl-2-picrylhydrazyl (DPPH) (IC50: 0.055 mg/mL) and alkyl radicals (IC50: 0.349 mg/mL). High performance liquid chromatography finger printing analysis of SC revealed quercetin (QCT) as one of the major constituents compared with reference standard. QCT also inhibited the excessive release of NO, and inhibited the increased expressional levels of IL-6, iNOS and COX-2 in LPS-stimulated BV-2 cells.. Our results indicated that SC inhibited the LPS-stimulated neuroinflammatory responses in BV-2 microglia via regulation of NF-κB signaling. The antioxidant active constituents of SC might be partly involved in delivering such effects. Based on the traditional claims and our present results SC can be potentially used in treating inflammatory-mediated neurodegenerative diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Cell Line; Cyclooxygenase 2; I-kappa B Proteins; Inflammation; Interleukin-6; Lipopolysaccharides; Mice; Microglia; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Synthase Type II; Phytotherapy; Picrates; Plant Extracts; Quercetin; Saururaceae; Signal Transduction; Tumor Necrosis Factor-alpha

Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation. Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity. We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease. We designed and synthesized 10 SA derivatives according to their chemical structures. Preliminary screening of the compounds involved scavenging hydroxyl radicals and 2,2-diphenyl-1-picrylhydrazyl (DPPH(⋅)), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs. 1-Acetyl-sinapic acyl-4-(3'-chlorine-)benzylpiperazine (SA9) had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo. Thus, the effect of SA9 was further studied. SA9 inhibited tumor necrosis factor α-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs. In vivo, result of face-to-face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule-1 in mouse aortic intima. To study the molecular mechanism, results from luciferase assay, nuclear translocation of NF-κB, and Western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-κB activation in ECs. SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs. It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Aorta; Biphenyl Compounds; Cell Adhesion; Coumaric Acids; Croton Oil; Ear; Edema; Endothelial Cells; Endothelium, Vascular; Free Radical Scavengers; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Monocytes; NF-kappa B; Oxidative Stress; Picrates; Tumor Necrosis Factor-alpha

Citrus medica L. commonly known as Otroj, is an important medicinal plant reputed for its nutritious and therapeutic uses. The present work was undertaken to investigate the protective effect of the ethanolic extract of otroj (EEOT) against isoproterenol (ISO)-induced cardiotoxicity in rats. In addition, the antioxidant activity and the phenolic and flavonoidal contents were determined. Rats were administered EETO (250 and 500 mg/kg) or vehicle orally for 15 days along with ISO (85 mg/kg, s.c.) on the 14th and 15th day. ISO induced cardiac dysfunction, increased lipid peroxidation and alteration of myocyte-injury specific marker enzymes. ISO also showed an increase in levels of plasma cholesterol, triglycerides (TG), LDL-C, and VLDL-C. Moreover, the histological investigations showed myocardial necrosis and inflammation. EETO treatment brought the above parameters towards normal level. Moreover, in vitro DPPH radical scavenging and β-carotene-linoleic acid tests of the EEOT exhibited a notable antioxidant activity in both assays used. In addition, histopathological examination reconfirmed the protective effects of EEOT. Thus, the present study reveals that C. medica alleviates myocardial damage in ISO-induced cardiac injury and demonstrates cardioprotective potential which could be attributed to its potent antioxidant and free radical scavenging activity.

Topics: Animals; Antioxidants; Biomarkers; Biphenyl Compounds; Cardiomyopathies; Citrus; Female; Flavonoids; Inflammation; Isoproterenol; Lipid Peroxidation; Lipids; Male; Myocardium; Necrosis; Oxidative Stress; Phenols; Phytotherapy; Picrates; Plant Extracts; Rats; Rats, Wistar; Tachycardia

The polyherbal eye drop (Itone™) is a mixture of aqueous distillates of nineteen traditionally used ingredients that sum up to impart potency to the formulation and make it a useful adjunct in various ocular pathologies. However, as there have been no controlled experimental studies accounting to the above claim, therefore, the present study was designed to evaluate the polyherbal formulation (PHF) for antiangiogenic, anti-inflammatory, anticataract, antioxidant and cytotoxicity in addition to the evaluation of intraocular penetration of PHF in rabbit eyes using LC-MS/MS.. Antiangiogenic activity of the PHF was evaluated using in ovo chick chorio-allantoic membrane (CAM) assay and in vivo cautery induced corneal neovascularization assay in rats. Anticataract potential was evaluated using steroid induced cataract in developing chick embryos, sodium selenite induced cataract in rat pups and galactose induced cataract in rats. The antioxidant activity was evaluated using di-phenyl picryl hydrazyl (DPPH) radical scavenging assay. Anti-inflammatory activity was evaluated in vitro using inhibition of LTB4 formation in human WBCs and in vivo using carrageenan induced paw edema assay in rats. The cytotoxicity was evaluated against HeLa cancer cell lines using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore evaluation of the intraocular penetration of the PHF was carried out in rabbit eyes via aqueous humor paracentesis and further analysis using LC-MS/MS.. PHF significantly inhibited VEGF induced proliferation of new blood vessels in CAM assay and inhibited the cautery induced corneal neovascularization in rats. Additionally, PHF showed noticeable delay in the progression of cataract in the selenite and galactose induced cataract models whereby the PHF treated lenses were graded for stages II and III respectively. However, the PHF did not show any anticataract activity in the hydrocortisone induced cataract model. Moreover, PHF exhibited anti-inflammatory activity whereby it showed 39.34% inhibition of LTB4 formation and significantly inhibited carrageenan induced paw edema in rats. Eight compounds of PHF viz. camphor, casticin, curcumin-II, quercetin, rosmarinic acid, γ-terpinene, β-pinene and dipentene exhibited transcorneal penetration in rabbit eyes.. The significant antiangiogenic and anti-inflammatory activities evinced by the PHF merits further investigation for ocular neovascular and inflammatory diseases in humans.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Aqueous Humor; Biphenyl Compounds; Blood Vessels; Carrageenan; Cataract; Chick Embryo; Cornea; Edema; Eye; Female; Galactose; HeLa Cells; Humans; Hydrocortisone; Inflammation; Lens, Crystalline; Leukocytes; Leukotriene B4; Male; Medicine, Ayurvedic; Models, Animal; Ophthalmic Solutions; Phytotherapy; Picrates; Plant Extracts; Rabbits; Rats; Rats, Wistar; Sodium Selenite; Steroids; Vascular Endothelial Growth Factor A

Various parts of the perennial herb Hilleria latifolia (Lam.) H. Walt. (Family: Phytolaccaceae) are used in Ghanaian traditional medicine for the treatment of several inflammatory-related disorders. The present study examined the anti-inflammatory effect of an ethanolic extract of the aerial parts of Hilleria latifolia (HLE) in acute and chronic inflammation models. Since free radicals and reactive oxygen species are implicated in inflammatory diseases, the antioxidant potential of HLE was also investigated in in vitro experimental models. HLE (10-300 mg kg(-1), p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot oedema in 7-day old chicks. Similarly, the NSAID diclofenac (10-100 mg kg(-1), i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3-3 mg kg(-1), i.p.) dose-dependently reduced the oedema in both pre-emptive and curative treatments. In the Freund's adjuvant induced-arthritis model in rats, HLE as well as the positive controls, dexamethasone and methotrexate, showed significant anti-arthritic properties when applied to established adjuvant arthritis. HLE (10-300 mg kg(-1), p.o.) significantly reduced oedema in the ipsilateral paw of rats but failed to prevent systemic arthritic spread. The DMARD methotrexate (0.1-1 mg kg(-1), i.p.) and dexamethasone (0.3-3 mg kg(-1), i.p.) reduced significantly the total polyarthritic oedema as well as the spread of the arthritis from the ipsilateral to the contralateral paws of the treated animals. The extract (0.03-1.00 mg ml(-1)) exhibited Fe(3+) reducing activity, scavenged DPPH and prevented lipid peroxidation. These findings suggest that the extract exerts in vivo anti-inflammatory activity after oral administration and also has antioxidant properties which may contribute to its activity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Biphenyl Compounds; Carrageenan; Chickens; Chronic Disease; Dexamethasone; Dose-Response Relationship, Drug; Edema; Free Radicals; Ghana; Inflammation; Iron Compounds; Lipid Peroxidation; Male; Methotrexate; Phytolaccaceae; Phytotherapy; Picrates; Plant Components, Aerial; Plant Extracts

The leaves of Michauxia species are used for the treatment of wounds in Turkish traditional medicine. In the present study, wound healing, anti-inflammatory and antioxidant activities of the extracts obtained from the root and herb of 5 species of Michauxia collected in different parts of Turkey were evaluated.. In vivo incision and excision wound models were used in order to assess the wound healing effects of the methanolic extracts of the plants. Skin samples were also evaluated histopathologically. In vivo inhibitory effect of the extracts on acetic acid-induced increase in capillary permeability was studied for the assessment of anti-inflammatory activity. TBA (thiobarbituric acid) test, qualitative and quantitative DPPH (2,2-diphenyl-1-picrylhydrazyl) tests were used to evaluate the antioxidant activity.. Noteworthy wound healing activity was observed for the ointment formulation prepared with 1% Michauxia nuda (root) and Michauxia tchihatchewii (herb) extracts. The results of histopathological evaluation supported the outcome of incision and excision wound models. Moreover, the Michauxia nuda (root) exerted remarkable anti-inflammatory effect. The highest antioxidant activity was observed with the ethyl acetate extract of Michauxia tchihatchewii herb.. The experimental study revealed that Michauxia displays remarkable wound healing and anti-inflammatory and antioxidant activities.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Campanulaceae; Capillary Permeability; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Lipid Peroxidation; Male; Mice; Picrates; Plant Extracts; Plant Leaves; Plant Roots; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Skin; Thiobarbituric Acid Reactive Substances; Turkey; Wound Healing

Ammannia baccifera L. has been reported as folklore remedy for the treatment of inflammation and tumor in the state of Rajasthan, India.. The present study was designed to investigate the antioxidant, anti-inflammatory and anti-nociceptive effects of the methanol extract from the aerial parts of Ammannia baccifera under in vitro and in vivo models.. The in vitro antioxidant activity of the extract was measured using DPPH, superoxide, hydroxyl and nitric oxide radicals. The anti-inflammatory activity was evaluated using carrageenan induced paw edema. Analgesic activity of the methanol extract was estimated against acetic acid-induced writhing and hot plate methods.. The IC(50) value for free radical scavenging activity of this extract was significantly superior over the positive standards butylated hydroxyl anisole (BHA) and rutin. The extract exhibited significant anti-inflammatory and analgesic activities at the dose of 100 and 200mg/kg p.o. The analgesic effect of the higher dose of the extract (200mg/kg) was comparable with the standard drugs aspirin and morphine.. The present study scientifically validated the traditional use of this plant against inflammation.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Behavior, Animal; Biphenyl Compounds; Carrageenan; Edema; Hot Temperature; India; Inflammation; Inhibitory Concentration 50; Lythraceae; Male; Medicine, Traditional; Mice; Mice, Inbred Strains; Pain; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species

Cyathula prostrata (Linn) Blume (Amaranthaceae) is an annual herb widely used traditionally in the treatment of various inflammatory and pain related health disorders in Nigeria. The aim of this study is to evaluate the anti-inflammatory, analgesic and antioxidant activities of the methanolic extract of Cyathula prostrata (Linn) Blume.. The anti-inflammatory (phorbol 12-myristate 13-acetate (PMA)-induced reactive oxygen species (ROS), lipopolysaccharide (LPS) induced nitric oxide production in U937 macrophages, LPS-induced COX-2 expression, carrageenan-induced rat paw oedema, arachidonic acid-induced ear oedema and xylene-induced ear oedema), analgesic (acetic acid-induced writhing and hot plate tests) and antioxidant activities (DPPH [1,1-diphenyl-2-picrylhydrazyl] and lipid peroxidation assays) activities of the plant extract were investigated.. The methanolic extract of Cyathula prostrata did not show inhibitory activity in the in vitro PMA-induced reactive oxygen species, LPS-induced nitric oxide production and LPS-induced COX-2 expression assays. In the in vivo anti-inflammatory assays, the extract (50, 100 and 200mg/kg) showed a significant (P<0.05) dose-dependent inhibition in the carrageenan, arachidonic acid and xylene-induced tests. Cyathula prostrata produced a significant (P<0.05, 0.001) dose-dependent inhibition in the acetic acid and hot plate analgesic tests respectively. The plant extract did not exhibit any antioxidant activity in the DPPH and lipid peroxidation assays.. The results suggest that the methanolic extract of Cyathula prostrata possesses anti-inflammatory and analgesic activities and this authenticates the use of the plant in the traditional treatment of ailments associated with inflammation and pain.

Topics: Acetic Acid; Amaranthaceae; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Behavior, Animal; Biphenyl Compounds; Carrageenan; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hot Temperature; Humans; Inflammation; Inflammation Mediators; Lipid Peroxidation; Lipopolysaccharides; Macrophages; Male; Methanol; Mice; Motor Activity; Nitric Oxide; Oxidative Stress; Pain; Pain Threshold; Phytotherapy; Picrates; Plant Preparations; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species; Solvents; Tetradecanoylphorbol Acetate; U937 Cells; Xylenes

Alders exhibit several uses in different areas and also offer some nutritional and medicinal values. The bark and leaves from black alder [Alnus glutinosa (L.) Gaertn] are used in folk medicine for the treatment of inflammatory processes and other health disorders. This study assessed if an extract of A. glutinosa stem bark exhibits some biological properties linked to improving the inflammatory state, which could partly justify its ethnopharmacological use. Therefore, various aspects of antioxidant activity as well as the effect on tumor necrosis factor-α (TNF-α) production were evaluated. The phytochemical study revealed the presence of terpenes, saponins, tannins, flavonoids, and anthraquinones (by high-performance thin-layer chromatography). The betulinic acid content in the extract, determined by reversed-phase high-performance liquid chromatography (validated method), was 0.72±0.027%. In addition, high amounts for total phenols as well as flavonoids were determined. The extract exhibited a 2,2'-diphenylpicrylhydrazyl radical scavenging capacity similar to that of ascorbic acid and had a significant effect on superoxide anion scavenging, superior to that of ascorbic acid. It was also able to protect HeLa cells from induced oxidative stress. In the TNF-α assay, levels of this citokine were depressed by the extract in HL-60 cells. To test the effect of the extract on cell proliferation, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. According to the results, the antioxidant properties displayed by the extract of A. glutinosa stem bark, together with the effect on TNF-α levels, suggest that these activities, linked to a successful reduction in inflammatory processes, may support, in part, its ethnopharmacological use.

Topics: Alnus; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Cell Proliferation; HeLa Cells; Humans; Inflammation; Oxidative Stress; Phytotherapy; Picrates; Plant Extracts; Tumor Necrosis Factor-alpha

Oxidative stress and inflammation are related to several chronic diseases including cancer. Actinidia callosa var. ephippioides (ACE) is a special folk medicinal plant from Taiwan. The aim of this study is to evaluate the antioxidant, anti-inflammatory, and antiproliferative activities of the methanol extract and fractions from the stem of ACE. Trolox Equivalent Antioxidant Capacity (TEAC), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, total phenolic content, flavonoid content, inhibition on nitric oxide (NO) productions by LPS-induced RAW264.7 cell, and on lung cancer cell proliferation were employed. Among all fractions, ethyl-acetate fraction (EA-ACE) showed higher TEAC, DPPH radical scavenging activities, polyphenol and flavonoid contents, respectively. EA-ACE also decreased the LPS-induced NO production and expressions of inducible nitric-oxide synthase (iNOS) in RAW264.7 cells. EA-ACE had the highest antiproliferative activity with an IC(50) (The concentrations required for inhibition of 50% of cell viability) of 469.17 ± 3.59 μg/mL. Catechin also had good effects in the antioxidant and anti-inflammatory activities. Catechin might be an important bioactive compound in the stem of ACE. The above experimental data indicated that the stem of ACE is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds.

Topics: Actinidia; Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Catechin; Cell Line; Cell Proliferation; Chromans; Flavonoids; Free Radical Scavengers; Inflammation; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Phytotherapy; Picrates; Plant Extracts; Plant Stems; Polyphenols

This study was designed to evaluate the anti-inflammatory action of four dihydroxy flavone derivatives; 3,3'- dihydroxy flavone, 5,6-dihydroxy flavone, 3,7-dihydroxy flavone and 6,3'-dihydroxy flavone and to further investigate the multiple cellular mechanisms underlying the anti-inflammatory effect of these compounds. The effect of dihydroxy flavones on acute inflammation was studied in rats employing carrageenan induced hind paw edema method. Further, the role of proinflammatory cytokines like TNF-α and IL-1β, cyclooxygenases (COX-1 and COX-2), and free radicals in the action of flavone derivatives was investigated using in vitro assays. All the four dihydroxy flavone derivatives exhibited time and dose dependent inhibition of carrageenan induced paw edema. In addition, the investigated compounds inhibited both the isoforms of cyclooxygenase and cytokines in a concentration dependent manner and also suppressed the release of reactive oxygen species. The anti-inflammatory effect of dihydroxy flavones may be through mechanisms that involve an interaction with cyclooxygenases, cytokines and reactive oxygen species.

Topics: Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Cyclooxygenase 1; Cyclooxygenase 2; Cytokines; Dose-Response Relationship, Drug; Edema; Flavones; Free Radical Scavengers; Free Radicals; Hindlimb; Inflammation; Male; Nitrates; Picrates; Rats; Rats, Wistar

Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay.. In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 μg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher.. Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.

Topics: alpha-Tocopherol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biphenyl Compounds; Carrageenan; Cell Movement; Doxycycline; Edema; Formaldehyde; Inflammation; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred Strains; Minocycline; Neutrophils; Nitric Oxide Synthase Type II; Oxidation-Reduction; Pain; Pain Measurement; Peritonitis; Peroxidase; Picrates; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Sideritis species (Lamiaceae) are widely used as herbal tea and have been used in folk medicine for their anti-inflammatory, anti-rheumatic, digestive, and antimicrobial activities in Turkey. Sideritis dichotoma Huter., Sideritis erythrantha Boiss. var. cedrotorum, and Sideritis vuralii H. Duman et Başer are available as commercial products in Turkey.. The antiradical activities of the various solvent extracts of Sideritis species are investigated here for the first time.. Plant samples were sequentially extracted with n-hexane, dichloromethane, methanol, and aqueous methanol (50%, v/v) in Soxhlet apparatus. The extracts of Camellia sinensis (L.) Kuntze (Theaceae) were also prepared for use as a positive control. Total phenolics, iron(III) reductive effects, and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging activities of the all extracts were measured colorimetrically.. The aqueous MeOH and MeOH extracts contained the highest amount of total phenols, whereas the n-hexane extract contained the lowest amounts. The polar extracts of C. sinensis showed higher antiradical activity and also iron(III) reductive effects than the Sideritis species; however, the non-polar extracts of Sideritis species were found to be more active than those from C. sinensis in the iron(III) reductive assay and in the DPPH(•) assay as well. But none of the extracts was found to be as active as with positive controls, viz., ascorbic acid, butylated hydroxyanisole (BHA), and Trolox.. These results can be shown to have antioxidant activities of these Sideritis species and support the ethnopharmacological use of these Sideritis plants.

Topics: Antioxidants; Biphenyl Compounds; Free Radical Scavengers; Inflammation; Iron; Medicine, Traditional; Phenols; Phytotherapy; Picrates; Plant Components, Aerial; Plant Extracts; Sideritis; Turkey

Aristotelia chilensis leaves (Elaeocarpaceae) are used in Chilean folk medicine to treat pain and inflammation. A bioguided study was carried out on serial extracts (hexane, dichloromethane, methanol, aqueous extract (INFU) and a crude mixture of alkaloids (ALK-MIX). All extracts were evaluated for (1) topical administration against both arachidonic acid and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation in mice and (2) per-os administration against inflammation by λ-carrageenan-induced paw oedema in guinea-pigs and (3) topical analgesia in tail flick and formalin models and per-os writhing test in mice.. Greater anti-inflammatory effects were obtained against TPA with dichloromethane extract and methanol extract (63.9 and 66.0%, respectively). INFU showed the most potent effect (56.2%) against arachidonic acid. Greater effects were obtained in the writhing test with hexane and dichloromethane extracts (89.2% both). In the topical analgesia models, all the extracts and ALK-MIX were active with exception of the hexane extract in the formalin assay. In tail flick test, ALK-MIX and the methanol extract were the most active (58.2 and 55.2%, respectively). In relation to the tail formalin assay, the methanol extract (74.1%) was the most active. Concerning antioxidant activity, both INFU and the methanol extract were the most active either in the inhibition of xanthine oxidase (52.9 and 62.7%, respectively) or in the DPPH free radical scavenging activity (EC50 (concentration that produced 50% of activity) = 12.1 and 9.7 µg/ml, respectively).. Aristoteline, aristone, serratoline and hobartinol were isolated from ALK-MIX. Ursolic acid, friedelin and quercetin 5,3'-dimethyl ether were present in the dichloromethane extract while quercetin 3-O-β-D-glucoside and kaempferol were present in the methanol extract. From INFU were isolated protopine, aristoteline and caffeic and ferulic acids.. The effects of A. chilensis are herein demonstrated, validating its use in traditional medicine. Protopine is reported for the first time in Elaeocarpaceae.

Topics: Administration, Topical; Alkaloids; Analgesia; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Behavior, Animal; Biphenyl Compounds; Carrageenan; Chile; Edema; Elaeocarpaceae; Female; Formaldehyde; Guinea Pigs; Inflammation; Male; Medicine, Traditional; Mice; Mice, Inbred Strains; Pain; Phorbol Esters; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Xanthine Oxidase

The purpose of the current study was to determine the anti-obesity and anti-inflammatory effects of an extract of purple sweet potatoes (PSPs) on 3T3-L1 adipocytes. For this purpose, differentiated 3T3-L1 adipocytes were treated with a PSP extract at concentrations of 1,000, 2,000, and 3,000 μg/mL for 24 hours. Then, we measured the changes in the sizes of the adipocytes, the secretion of leptin, and the mRNA/protein expression of lipogenic, inflammatory, and lipolytic factors after the treatment with the PSP extract. The PSP extract diminished leptin secretion, indicating that growth of fat droplets was suppressed. The extract also suppressed the expression of mRNAs of lipogenic and inflammatory factors and promoted lipolytic action. The antioxidative activity of the PSP extract was also measured using three different in vitro methods: 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity, ferric reducing ability potential assay, and chelating activity of transition metal ions. Taken together, our study shows that PSP extract has antilipogenic, anti-inflammatory, and lipolytic effects on adipocytes and has radical scavenging and reducing activity.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Anthocyanins; Anti-Inflammatory Agents; Anti-Obesity Agents; Antioxidants; Biphenyl Compounds; Blotting, Western; Cell Differentiation; Inflammation; Ipomoea batatas; Leptin; Lipolysis; Mice; Picrates; Plant Extracts; Real-Time Polymerase Chain Reaction

UV-induced inflammation and reactive oxygen species formation are involved in the development of melanoma. Natural products like 5β-scymnol and CO(2)-supercritical fluid extract (CO(2)-SFE) of mussel oil contain anti-inflammatory and antioxidant properties that may aid in reducing the deleterious effects of UV radiation. Therefore, their effect on the release of the proinflammatory cytokine, tumour necrosis factor-α (TNF-α), from UVB-irradiated human melanocytic cells was examined. Human epidermal melanocytes (HEM) and MM96L melanoma cells were exposed to UVB radiation and IL-1α. Cell viability and TNF-α levels were determined 24 hours after-irradiation while p38 mitogen-activated protein kinase (MAPK) activation was observed at 15 min after-irradiation. When α-tocopherol, CO(2)-SFE mussel oil, and 5β-scymnol were added to the UVB-irradiated HEM cells treated with IL-1α, TNF-α levels fell by 53%, 65%, and 76%, respectively, while no inhibition was evident in MM96L cells. This effect was not due to inhibition of the intracellular p38 MAPK signalling pathway. These compounds may be useful in preventing inflammation-induced damage to normal melanocytes.

Topics: Animals; Antioxidants; Biphenyl Compounds; Cell Survival; Cells, Cultured; Dietary Supplements; Humans; Hydrogen Peroxide; Inflammation; Interleukin-1alpha; Iron; Melanocytes; Melanoma, Experimental; Mice; p38 Mitogen-Activated Protein Kinases; Picrates; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Ultraviolet Rays

Our previous report has showed that demethoxycurcumin (DMC), a natural derivative of curcumin (Cur), exhibited stronger inhibitory activity on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production compared with Cur in lipopolysaccharide (LPS) activated rat primary microglia. In the present study, the effect and possible mechanism of DMC on the production of pro-inflammatory mediators in LPS-activated N9 microglial cells were further investigated. The results showed that DMC significantly suppressed the NO production induced by LPS in N9 microglial cells through inhibiting the protein and mRNA expression of inducible NO synthase (iNOS). DMC also decreased LPS-induced TNF-alpha and IL-1beta expression at both transcriptional and protein level in a concentration-dependent manner. Further studies revealed that DMC blocked IkappaBalpha phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). Moreover, the level of intracellular reactive oxygen species (iROS) was significantly increased by LPS, which is mainly mediated by the up-regulated expression of gp91phox, the catalytic subunit of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. Both DMC and Cur could markedly decrease iROS production and the expression of NADPH oxidase induced by LPS, with more potent inhibitory activity of DMC. In summary, these data suggest that DMC exerts its in vitro anti-inflammatory effect in LPS-activated N9 microglial cells by blocking nuclear factor-kappaB (NF-kappaB) and MAPKs activation, which may be partly due to its potent down-regulation of the NADPH-derived iROS production.

Topics: Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Blotting, Western; Cell Survival; Curcumin; Diarylheptanoids; Down-Regulation; Inflammation; Interleukin-1beta; Lipopolysaccharides; Macrophage Activation; Mice; Microglia; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Picrates; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tumor Necrosis Factor-alpha

A series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti-inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti-inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti-inflammatory activity of these dual-acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Aspirin; Biphenyl Compounds; Croton Oil; Disease Models, Animal; Drug Design; Hydroxybenzoates; Inflammation; Lipid Peroxidation; Male; Mice; Molecular Structure; Picrates; Stomach Ulcer; Structure-Activity Relationship

Pistacia lentiscus has traditionally been used in the treatment of many diseases. Its resin was investigated for its mineral contents, anti-inflammatory and antioxidant activities in rats.. Inhibition of carrageenan induced edema was used to evaluate anti-inflammatory activity. Fe2+ chelating ability, 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) and nitric oxide scavenging activities were used to evaluate antioxidant activities and mineral contents were determined by atomic absorption spectroscopy. Gallic acid content was determined by HPLC.. Resin produced statistically significant inhibition of edema at all doses when compared to the control groups. A 100% inhibition of inflammation was observed at 800 mg/kg i.p. Resin exhibit no toxicity up to 3 g/kg body weights i.p. in mice. Weak DPPH and nitric oxide scavenging activities were observed but showed good Fe2+ chelating ability (IC50 = 162 microg ml(-1)). The amount of elements was decreased in the order: Cu > Fe, Zn > Mn > Ni, Cd. Gallic acid content was 0.1 mg/g resin.. These experimental data support the use of Pistacia lentiscus resin as an antiinflammatory and antioxidant agent.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Carrageenan; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Ferrous Compounds; Ferrozine; Flavonoids; Free Radical Scavengers; Gallic Acid; Inflammation; Iron Chelating Agents; Male; Mastic Resin; Mice; Nitric Oxide; Picrates; Rats; Rats, Wistar; Resins, Plant; Spectrophotometry, Atomic

The chromatographic separation of MeOH extract from Clerodendron trichotomum Thunberg leaves led to the isolation of three phenylpropanoid compounds. Using spectroscopic methods, the structures of these compounds were determined as beta-(3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(4-O-caffeoyl)-glucopyranoside, acteoside (verbascoside) (1), beta-(3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(6-O-caffeoyl)-glucopyranoside, isoacteoside (2), beta-(3', 4'-dihydroxyphenyl) ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-glucopyranoside, and decaffeoylacteoside (3). We measured the anti-inflammatory activity of these three phenylpropanoid compounds both in vitro (DPPH reduction assay, TBARS assay on Cu (2+)-induced oxidized LDL, PGE(2) assay) and in vivo (acetic acid induced vascular permeability in mice and carrageenan-induced hind paw edema in rats). 80% methanol fraction and acteoside had the activity.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Capillary Permeability; Carrageenan; Catechols; Cell Line; Clerodendrum; Dinoprostone; Disaccharides; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Glucosides; Humans; Inflammation; Magnetic Resonance Spectroscopy; Mast Cells; Mice; Molecular Structure; Phenols; Picrates; Plant Leaves; Rats; Thiobarbituric Acid Reactive Substances

Trioxsalen (TRX) is a 4,5',8-trimethylated psoralen analog presenting interesting biological activities when irradiated with UVA light. A series of TRX derivatives, which where obtained by its chemical modification and incorporation of a variety of unsaturated functions at position 4' of the psoralen ring-system, were evaluated for their antioxidant activity and their inhibitory activity on soybean lipoxygenase (LOX) and lipid peroxidation. The reducing properties of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay and found to be very low, in the range 0-14%, with the exception of the hydroxamic acid 6 which showed almost identical activity to BHT. TRX derivative 3 significantly inhibited LOX, with IC(50) 9.4 muM. With the exception of TRX, all tested analogs inhibited lipid peroxidation in the range of 35-91%. The most potent compound, namely TRX derivative 3, was studied for its anti-inflammatory activity in vivo on rat paw edema induced by carrageenan, and was found to be of almost identical activity to indomethacin. The results of the biological tests are discussed in terms of structural characteristics.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Carrageenan; Edema; Female; Free Radical Scavengers; Glycine max; Hindlimb; Indomethacin; Inflammation; Inhibitory Concentration 50; Lipid Peroxidation; Lipoxygenase; Lipoxygenase Inhibitors; Male; Picrates; Rats; Trioxsalen

The present study was aimed to investigate the activity of Thai medicinal plants on inflammation caused by Propionibacterium acnes in terms of free radical scavenging and cytokine reducing properties. P. acnes have been recognized as pus-forming bacteria triggering an inflammation in acne. Antioxidant activity was determined by DPPH scavenging and NBT reduction assay. The result showed that Garcinia mangostana possessed the most significant antioxidant activity and reduced reactive oxygen species production. Houttuynia cordata, Eupatorium odoratum, and Senna alata had a moderate antioxidant effect. In addition, Garcinia mangostana extracts could reduce the TNF-alpha production as determined by ELISA. Garcinia mangostana was highly effective in scavenging free radicals and was able to suppress the production of pro-inflammatory cytokines. This study has identified the promising source of anti-inflammatory agent which could be useful in treatment of acne vulgaris.

Topics: Acne Vulgaris; Antioxidants; Biphenyl Compounds; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Garcinia mangostana; Humans; Inflammation; Leukocytes, Mononuclear; Microbial Sensitivity Tests; Nitroblue Tetrazolium; Phytotherapy; Picrates; Plant Extracts; Propionibacterium acnes; Tumor Necrosis Factor-alpha

Oxidized low-density lipoprotein (ox-LDL) plays an important in the development of atherosclerosis by stimulating the production of reactive oxygen species in endothelial cells, and thereby up-regulating vascular cell adhesion molecule-1 (VCAM-1). The objectives of the present study were to determine the effects of azelnidipine, a new calcium channel blocker, on the expression of VCAM-1 induced by 7-ketocholesterol, components of ox-LDL, and tumor necrosis factor-alpha (TNF-alpha). The scavenging activities of azelnidipine against superoxide, hydroxyl, and carbon-centered radicals were determined by electron spin resonance assay. The levels of intracellular reactive oxygen species were determined fluorometrically with the use of dichlorodihydrofluorescein diacetate (H(2)DCF-DA). Human aortic endothelial cells and U937 were used as endothelial cells and monocytic cells, respectively. The surface expression and mRNA levels of VCAM-1 were determined by enzyme immunoassay and RT-PCR performed on endothelial cell monolayers stimulated with 7-ketocholesterol or TNF-alpha. The numbers of monocytic cells adhering on the stimulated endothelial cells were counted in the microscopic fields. Translocation of p65 protein to the nucleus was estimated by fluorescence microscopy. Azelnidipine, but not nifedipine, reduced the signal intensity of 1,1-diphenyl-2-picrylhydrazyl radicals. Azelnidipine scavenged hydroxyl radicals, but not superoxide radicals. Intracellular levels of reactive oxygen species and RelA (p65) nuclear translocation in stimulated endothelial cells were reduced by azelnidipine. Azelnidipine significantly inhibited the expression of protein and mRNA of VCAM-1, and prevented the U937 cell adhesion to endothelial cells treated with 7-ketocholesterol or TNF-alpha. These results suggest that azelnidipine works as an anti-atherogenic agent by inhibiting the reactive oxygen species-dependent expression of VCAM-1 induced by 7-ketocholesterol and TNF-alpha.

Topics: Aorta; Azetidinecarboxylic Acid; Biphenyl Compounds; Calcium Channel Blockers; Cell Adhesion; Cell Membrane; Cyclic N-Oxides; Dihydropyridines; Dose-Response Relationship, Drug; Endothelial Cells; Fluoresceins; Free Radical Scavengers; Gene Expression Regulation; Humans; Hydrazines; Indicators and Reagents; Inflammation; Ketocholesterols; Monocytes; NF-kappa B p50 Subunit; Nifedipine; Picrates; Protein Transport; Reactive Oxygen Species; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha; U937 Cells; Vascular Cell Adhesion Molecule-1

Three flavonoids, gnaphaliin, pinocembrin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their antioxidant and/or scavenger properties and in vivo in different models of inflammation. In vitro tests included lipid peroxidation in rat liver microsomes, superoxide radical generation in the xanthine/xanthine oxidase system and the reduction of the stable radical 1,1-diphenyl-2-pycryl-hydrazyl (DPPH). Acute inflammation was induced by application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to the mouse ear or by subcutaneous injection of phospholipase A(2) or serotonin in the mouse paw. Eczema provoked on the mouse ear by repeated administration of TPA was selected as a model of chronic inflammation. The flavonoids were assayed against sheep red blood cell-induced mouse paw oedema as a model of delayed-type hypersensitivity reaction. The most active compound, both in vitro and in vivo, was tiliroside. It significantly inhibited enzymatic and non-enzymatic lipid peroxidation (IC(50)=12.6 and 28 microM, respectively). It had scavenger properties (IC(50)=21.3 microM) and very potent antioxidant activity in the DPPH test (IC(50)=6 microM). In vivo, tiliroside significantly inhibited the mouse paw oedema induced by phospholipase A(2)(ED(50)=35.6 mg/kg) and the mouse ear inflammation induced by TPA (ED(50)=357 microg/ear). Pinocembrin was the only flavonoid that exhibited anti-inflammatory activity in the sheep red blood cell-induced delayed-type hypersensitivity reaction. However, only tiliroside significantly reduced the oedema and leukocyte infiltration induced by TPA. As in the case of other flavonoids, the anti-inflammatory activity of tiliroside could be based on its antioxidant properties, although other mechanisms are probably involved.

Topics: Animals; Anti-Inflammatory Agents; Benzopyrans; Biphenyl Compounds; Female; Flavanones; Flavonoids; Free Radical Scavengers; Helichrysum; Humans; Hydrazines; Hypersensitivity, Delayed; In Vitro Techniques; Inflammation; Leukocytes; Lipid Peroxidation; Mice; Microsomes, Liver; Peroxidase; Phytotherapy; Picrates; Plant Extracts; Rats; Rats, Wistar; Sheep; Superoxides

The in vitro antioxidative activities of various kinds of vinegar were investigated by using a linoleic acid autoxidation model detected by the thiobarbituric acid (TBA) method and the 1,1-diphenyl-2-picrylhydrazyl radical system. An ethyl acetate extract of Kurosu (EK), a vinegar made from unpolished rice, exhibited the highest antioxidative activity in both systems. EK (5 mg) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema formation (14%) and myeloperoxidase activity (52%, P< 0.01) in female ICR mouse skin. Furthermore, EK significantly suppressed double TPA application-induced H2O2 generation (53%, P< 0.01) and lipid peroxidation determined by the TBA-reacting substance level (95 %, P< 0.01). In a two-stage carcinogenesis experiment with dimethylbenz[a]anthracene/TPA, EK significantly reduced the number of tumors per mouse by 36% (P<0.05) at 15 weeks after promotion. These results suggest that the antitumor-promoting effect may be partially due to the antioxidative properties of EK such as the decomposition of free radicals and interference with free radical-generating leukocytes.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetic Acid; Animals; Antioxidants; Bepridil; Biphenyl Compounds; Edema; Female; Free Radical Scavengers; Free Radicals; Hydrogen Peroxide; Inflammation; Lipid Peroxidation; Mice; Mice, Inbred ICR; Oryza; Picrates; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin E

Peroxynitrite (ONOO-) has been proposed as a mediator of gut inflammation and as an inducer of cell death by apoptosis. Phytolens (PHY), a water-soluble extract of polyphenolic antioxidants from nonsoy legumes (Biotics Research Corp, patent pending), was evaluated as a cytoprotective agent in human colonic (T84) and murine macrophage (RAW 264.7) cell lines. In the antioxidant testing, PHY showed a significant free radical scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and superoxide (O2.) radicals with an IC50 of 4.44 and 5.87 microg/ml against DPPH and O2., respectively. Apoptosis (DNA fragmentation) was measured by an ELISA technique. Cells were exposed to oxidative stress by treating them with peroxynitrite (100-300 microM) for 4 h in the presence and absence of PHY. Peroxynitrite elicited a dose-dependent increase in DNA fragmentation in both cell lines compared to the control group receiving decomposed ONOO-. PHY (10, 30, or 50 microg/ml) significantly attenuated the degree of apoptosis in T84 cells induced by ONOO- (P < 0.05). PHY (10-100 microg/ml) did not directly affect T84 cell viability or induce apoptosis after 4 h or overnight exposure. RAW 264.7 cells exposed to PHY alone (>30 microg/ml) for 4 h displayed decreased cell viability (P < 0.05) and increased apoptosis (P < 0.05). Phytolens may have beneficial effects on inflammation by attenuating peroxynitrite-induced apoptosis. The sparing of epithelial cells while compromising the viability of macrophages suggests that PHY may be beneficial in autoimmune disorders.

Topics: Animals; Antioxidants; Apoptosis; Bepridil; Biphenyl Compounds; Cell Division; Cell Line; Cell Survival; Colonic Neoplasms; DNA Fragmentation; Fabaceae; Flavonoids; Free Radical Scavengers; Humans; Inflammation; Macrophages; Nitrates; Phenols; Picrates; Plants, Medicinal; Polymers; Polyphenols; Rats; Superoxides