linoleic-acid and caffeic-acid

Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.

Topics: Animals; Benzoic Acid; Biomarkers; Caffeic Acids; Cell Line, Tumor; Cinnamates; Coumaric Acids; Cyclic AMP Response Element-Binding Protein; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases; GAP-43 Protein; Linoleic Acid; MAP Kinase Signaling System; Mice; Neurites; Neuroblastoma; Oleic Acid; Phosphorylation; Pleurotus; Propionates; Proto-Oncogene Proteins c-akt; Signal Transduction; Succinic Acid; Uridine

The TWIK-related K(+) channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs. It has been reported that TREK-1 -/- mice were more sensitive than wild-type mice to painful stimuli, suggesting that activation of TREK-1 could result in pain inhibition. Here we report the synthesis of a series of substituted caffeate esters (12a-u) based on the hit compound CDC 2 (cinnamyl 3,4-dihydroxyl-α-cyanocinnamate). These analogs were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid induced-writhing assay) leading to the identification a series of novel molecules able to activate TREK-1 and displaying potent analgesic activity in vivo.

Topics: Analgesics; Animals; Caffeic Acids; Cinnamates; Esters; Male; Mice; Models, Molecular; Pain; Potassium Channels, Tandem Pore Domain; Quantitative Structure-Activity Relationship; Xenopus

Caffeic acid (3,4-dihydroxycinnamic acid) is among the major hydroxycinnamic acids present in wine; sinapic acid, which is a potent antioxidant. It has also been identified as one of the active antioxidant. In the present study, the antioxidant properties of the caffeic acid were evaluated by using different in vitro antioxidant assays such as 2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, total antioxidant activity by ferric thiocyanate method, total reductive capability using the potassium ferricyanide reduction method, superoxide anion radical scavenging and metal chelating activities. alpha-Tocopherol, trolox, a water-soluble analogue of tocopherol, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) were used as the reference antioxidant compounds. At the concentrations of 10 and 30 microg/mL, caffeic acid showed 68.2 and 75.8% inhibition on lipid peroxidation of linoleic acid emulsion, respectively. On the other hand, 20 microg/mL of standard antioxidant such as BHA, BHT, alpha-tocopherol and trolox indicated an inhibition of 74.4, 71.2, 54.7 and 20.1% on peroxidation of linoleic acid emulsion, respectively. In addition, caffeic acid is an effective ABTS(+) scavenging, DPPH scavenging, superoxide anion radical scavenging, total reducing power and metal chelating on ferrous ions activities.

Topics: alpha-Tocopherol; Antioxidants; Benzothiazoles; Biphenyl Compounds; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Caffeic Acids; Chelating Agents; Chromans; Dose-Response Relationship, Drug; Emulsions; Ferricyanides; Ferrous Compounds; Free Radical Scavengers; Hydrazines; Iron; Linoleic Acid; Lipid Peroxidation; Picrates; Reducing Agents; Sulfonic Acids; Superoxides; Thiocyanates

Antioxidant activity of 24 ferulic acid related compounds together with 6 gallic acid related compounds was evaluated using several different physical systems as well as their radical scavenging activity. The radical scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) decreased in the order caffeic acid > sinapic acid > ferulic acid > ferulic acid esters > p-coumaric acid. In bulk methyl linoleate, test hydroxycinnamic acids and ferulic acid esters showed antioxidant activity in parallel with their radical scavenging activity. In an ethanol-buffer solution of linoleic acid, the activity of test compounds was not always associated with their radical scavenging activity. Ferulic acid was most effective among the tested phenolic acids. Esterification of ferulic acid resulted in increasing activity. The activity of alkyl ferulates was somewhat influenced by the chain length of alcohol moiety. When the inhibitory effects of alkyl ferulates against oxidation of liposome induced by AAPH were tested, hexyl, octyl, and 2-ethyl-1-hexyl ferulates were more active than the other alkyl ferulates. Furthermore, lauryl gallate is most effective among the tested alkyl gallates. These results indicated that not only the radical scavenging activity of antioxidants, but also their affinity with lipid substrates, might be important factors in their activity.

Topics: Antioxidants; Bepridil; Biphenyl Compounds; Buffers; Caffeic Acids; Coumaric Acids; Esterification; Ethanol; Free Radical Scavengers; Free Radicals; Gallic Acid; Hot Temperature; Linoleic Acid; Liposomes; Oryza; Picrates; Plant Structures; Solutions

The antioxidant activity of phenolic compounds isolated from Mesona procumbens Hemsl. (Hsian-tsao) was investigated. Hsian-tsao was extracted with various solvents, and the results showed that the fraction treated with acidic ethyl acetate (pH 2) possessed large amounts of phenolic compounds and a strong antioxidant activity on peroxidation of linoleic acid. The antioxidant activity (inhibition of peroxidation, IP%) of the acidic ethyl acetate of Hsian-tsao extract at 50 microg/mL (98.9%) was stronger than those of 50 microg/mL alpha-tocopherol (78%) and BHA at 10 microg/mL (90%). When fractionated with Amberlite XAD-7 gel chromatography, the acidic ethyl acetate fraction of Hsian-tsao extract was separated into four subfractions (A-D). Subfraction B, with high yield and strong antioxidant activity, was further isolated and purified and then identified as containing protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, and syringic acid by means of UV, EI-MS, and (1)H and (13)C NMR. The antioxidant capability of isolated compounds was also determined using the thiocyanate system and the erythrocyte ghost system. The results indicate that the phenolic acids could be important antioxidant components in Hsian-tsao, among which caffeic acid with the highest antioxidant activity and the greatest content is most important.

Topics: Acetates; alpha-Tocopherol; Antioxidants; Caffeic Acids; Drugs, Chinese Herbal; Gallic Acid; Hydroxybenzoates; Linoleic Acid; Magnetic Resonance Spectroscopy; Oxidation-Reduction; Phenols; Plant Extracts; Vanillic Acid

We previously found (I. Shureiqi et al., Carcinogenesis (Lond.), 20: 1985-1995, 1999; I. Shureiqi et al, J. Natl. Cancer Inst., 92: 1136-1142, 2000) that (a) 15-lipoxygenase-1 (15-LOX-1) protein and its product 13-S-hydroxyoctadecadienoic acid (13-S-HODE) are decreased; and (b) nonsteroidal anti-inflammatory drug (NSAID)-induced 15-LOX-1 expression is critical to NSAID-induced apoptosis in colorectal cancer cells expressing cyclooxygenase-2 (COX-2). We used the NSAIDs sulindac sulfone (COX-2-independent) and NS-398 (a COX-2 inhibitor) to assess NSAID upregulation of 15-LOX-1 in relation to COX-2 inhibition during NSAID-induced apoptosis in the DLD-1 (COX-2-negative) colon cancer cell line. We found that: (a) NSAIDs up-regulated 15-LOX-1, which preceded apoptosis; and (b) 15-LOX-1 inhibition blocked NSAID-induced apoptosis, which was restored by 13-S-HODE but not by its parent, linoleic acid. NSAIDs can induce apoptosis in colon cancer cells via up-regulation of 15-LOX-1 in the absence of COX-2.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Antithrombins; Apoptosis; Arachidonate 15-Lipoxygenase; Arachidonic Acid; Blotting, Western; Caffeic Acids; Cell Line; Colonic Neoplasms; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Hydroxyeicosatetraenoic Acids; Isoenzymes; Linoleic Acid; Linoleic Acids; Membrane Proteins; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Recombinant Proteins; Sulfonamides; Sulindac; Time Factors; Tumor Cells, Cultured; Up-Regulation

Caffeic acid phenethyl ester, an active component of propolis extract, inhibits 5-lipoxygenase in the micromolar concentration range. The inhibition is of an uncompetitive type, i.e. the inhibitor binds to the enzyme-substrate complex but not to the free enzyme. Caffeic acid phenethyl ester also exhibits antioxidant properties. At a concentration of 10 microM, it completely blocks production of reactive oxygen species in human neutrophils and the xanthine/xanthine oxidase system.

Topics: Antioxidants; Caffeic Acids; Hordeum; Humans; Kinetics; Linoleic Acid; Linoleic Acids; Lipoxygenase Inhibitors; Luminescent Measurements; Neutrophils; Oxidation-Reduction; Phenylethyl Alcohol; Reactive Oxygen Species; Xanthine; Xanthine Oxidase; Xanthines

Co-oxidation of chlorogenic acid, caffeic acid, aesculetin and lucigenin with linoleic acid and egg phosphatidyl choline leads to the formation of fluorescent polymer materials. The fluorescent products are more lipophylic, they have lower elution volumes on Sephadex LH-20 column than related phenols and they differ by their fluorescence and chromatographic properties considerably from polymer lipid peroxidation products. From the presence in the excitation fluorescence spectra of a band corresponding to the phenols it was concluded that the fluorophoric groups were similar in both cases. The data are discussed in terms of liquid phase peroxidation and the appearance of the fluorescent species are attributed to the production of molecular adducts as a result of lipid and phenoxyl radical recombination. The characteristics of products obtained are compared with properties of fluorescent "plant ageing" pigments accumulated in aged and damaged plant cells.

Topics: Acridines; Caffeic Acids; Chlorogenic Acid; Free Radicals; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Lipid Peroxides; Oxidation-Reduction; Phenols; Phosphatidylcholines; Pigments, Biological; Plant Physiological Phenomena; Spectrometry, Fluorescence; Umbelliferones