rosmarinic-acid and 6-hydroxy-2-5-7-8-tetramethylchroman-2-carboxylic-acid

Substantial studies have shown that curcumin, a dietary compound from turmeric, has beneficial effects on many diseases. However, curcumin rapidly degrades at physiological pH, making it difficult to interpret whether the observed actions of curcumin are from curcumin itself or its degradation products. Therefore, it is important to better understand the mechanisms involved in curcumin degradation and the roles of degradation in its biological actions.. Here, we show that a series of redox active antioxidants with diverse chemical structures, including gallic acid, ascorbate (vitamin C), tert-butylhydroquinone (TBHQ), caffeic acid, rosmarinic acid, and Trolox (a water-soluble analog of vitamin E), dramatically increased curcumin stability in phosphate buffer at physiological pH. When treated in basal cell culture medium in MC38 colon cancer cells, curcumin rapidly degraded with a half-life of several minutes and showed a weak antiproliferative effect; co-addition of antioxidants enhanced stability and antiproliferative effect of curcumin. Finally, co-administration of antioxidant significantly increased plasma level of curcumin in animal models.. Together, these studies strongly suggest that a redox-dependent mechanism plays a critical role in mediating curcumin degradation. In addition, curcumin itself, instead of its degradation products, is largely responsible for the observed biological actions of curcumin.

Topics: Animals; Antioxidants; Ascorbic Acid; Caffeic Acids; Cell Line, Tumor; Cell Proliferation; Chromans; Cinnamates; Curcumin; Depsides; Drug Stability; Gallic Acid; Hydrogen-Ion Concentration; Hydroquinones; Male; Mice; Oxidation-Reduction; Rosmarinic Acid

The present study aimed to evaluate acetylcholinesterase (AChE) inhibitory and antioxidant activities of Lamiaceae medicinal plants growing wild in Croatia. Using Ellman's colorimetric assay all tested ethanolic extracts and their hydroxycinnamic acid constituents demonstrated in vitro AChE inhibitory properties in a dose dependent manner. The extracts of Mentha x piperita, M. longifolia, Salvia officinalis, Satureja montana, Teucrium arduini, T. chamaedrys, T. montanum, T. polium and Thymus vulgaris at 1 mg/mL showed strong inhibitory activity against AChE. The antioxidant potential of the investigated Lamiaceae species was assessed by DPPH• scavenging activity and total antioxidant capacity assays, in comparison with hydroxycinnamic acids and trolox. The extracts differed greatly in their total hydroxycinnamic derivatives content, determined spectrophotometrically. Rosmarinic acid was found to be the predominant constituent in most of the investigated medicinal plants (by RP-HPLC) and had a substantial influence on their AChE inhibitory and antioxidant properties, with the exception of Teucrium species. These findings indicate that Lamiaceae species are a rich source of various natural AChE inhibitors and antioxidants that could be useful in the prevention and treatment of Alzheimer's and other related diseases.

Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Biphenyl Compounds; Cholinesterase Inhibitors; Chromans; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Cinnamates; Coumaric Acids; Depsides; Drug Discovery; Eels; Fish Proteins; Free Radical Scavengers; Free Radicals; Humans; Lamiaceae; Picrates; Plant Extracts; Plants, Medicinal; Rosmarinic Acid

Measurement of total antioxidant activity/capacity of polyphenols in various solvent media necessitates the use of cyclodextrins to solubilize lipophilic antioxidants of poor aqueous solubility. The inclusion complexes of the slightly water soluble antioxidant, rosmarinic acid (RA), with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (M-β-CD) were investigated for the first time. The effect of cyclodextrins (CDs) on the spectral features of RA was measured in aqueous medium using UV-vis and steady-state fluorescence techniques by varying the concentrations of CDs. The molar stoichiometry of RA-CD inclusion complexes was verified as 1:1, and the formation constants of the complexes were determined from Benesi-Hildebrand equation using fluorescence spectroscopic data. Among the CDs, maximum inclusion ability was measured in the case of M-β-CD followed by HP-β-CD, HE-β-CD, β-CD and α-CD. Solid inclusion complexes were prepared by freeze drying, and their functional groups were analyzed by IR spectroscopy. Antioxidant capacity of CD-complexed rosmarinic acid was measured to be higher than that of the lone hydroxycinnamic acid by the CUPric Reducing Antioxidant Capacity (CUPRAC) method. The mechanism of the TAC increase was interpreted as the stabilization of the 1-e oxidized o-catechol moiety of RA by enhanced intramolecular H-bonding in a hydrophobic environment provided by CDs, mostly by M-β-CD.

Topics: Antioxidants; Chromans; Cinnamates; Cyclodextrins; Depsides; Hydrogen-Ion Concentration; Kinetics; Rosmarinic Acid; Solutions; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

Described here is a novel spectrophotometric method for estimating antioxidant capacity in a 96-well microplate using as UV probes the conjugated triene triacylglycerols (TAGs) naturally present in tung oil. The TAGs of this commercially available oil contain around 86% eleostearic acid, an octadecatrienoic acid with conjugated trienes exhibiting strong UV absorption at 273 nm. In an oil-in-water emulsion at 37 degrees C, the azo initiator 2,2'-azobis(2-amidinopropane) dihydrochloride generated a constant flux of peroxy radicals, which destroyed the conjugated trienes. The absorbance decay at 273 nm, related to oxidative degradation of conjugated triene TAGs, was monitored in the absence and presence of various concentrations of antioxidants. To validate this new method, the antioxidant capacity of four phenolic compounds (gallic acid, (-)-epicatechin, chlorogenic acid, and rosmarinic acid) was measured using an area-under-the-curve calculation and expressed as Trolox equivalents, the value for Trolox being taken as reference. The order of efficacy was found to be rosmarinic acid > chlorogenic acid approximately epicatechin>Trolox>gallic acid, which can be partially explained by the number of catecholic moieties and the polarity of these antioxidants. Moreover, the conjugated autoxidizable triene (CAT) assay provided good insight into antioxidant behavior (i.e., retarder or chain breaker). The same molecules were then analyzed in 2,2-diphenyl-1-picrylhydrazyl and fluorescein-based oxygen radical absorbance capacity assays, and the results are discussed critically with respect to those obtained with the CAT assay. This new method may constitute an easy-to-use, sensitive, and high-throughput in vitro protocol for evaluation of the antioxidant capacity of pure molecules and natural extracts in lipid oxidation.

Topics: Antioxidants; Catechin; Chlorogenic Acid; Chromans; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Gallic Acid; Kinetics; Lipid Peroxidation; Microchemistry; Plant Oils; Reproducibility of Results; Rosmarinic Acid; Spectrophotometry, Ultraviolet; Triglycerides

Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by alpha-tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of the origin of this extreme antioxidative potency, we tested the antioxidative potency of 36 additional antioxidants and the dependence of their potency on the presence of PS in the liposomes. The results of these studies reveal that only 11 of the tested antioxidants possess similar antioxidative potency to that of Toc. These include trolox, butylated hydroxytoluene (BHT), curcumin, nordihydroguaiaretic acid (NDGA), diethylstilbestrol (DES), 2 of the 13 tested flavonoids (luteolin and 7,3',4'-trihydroxyflavone; T-414), alpha-naphthol, 1,5-, 1,6- and 1,7-dihydroxynaphthalenes (DHNs). Propyl gallate (PG), methyl syringate, rosmarinic acid, resveratrol, other flavonoids, as well as beta-naphthol, 1,2-, 1,3-, 1,4-, 2,3-, 2,6-, and 2,7-DHNs were either moderately antioxidative or pro-oxidative. For liposomes made of PLPC (250 microM) and PS (25 microM) the "lag" preceding copper-induced peroxidation (5 microM copper) was doubled upon addition of 30-130nM of the "super-active" antioxidants. We propose that the mechanism responsible for the extreme antioxidative potency against copper-induced peroxidation in PS-containing liposomes involves replenishment of the antioxidant in a ternary PS-copper-antioxidant complex. Based on structure-activity relationship of the 37 tested antioxidants, the "super-antioxidative potency" is attributed to the recycling of relatively stable semiquinone or semiquinone-like radicals.

Topics: Antioxidants; Butylated Hydroxytoluene; Chromans; Cinnamates; Copper; Curcumin; Depsides; Diethylstilbestrol; Flavonoids; Liposomes; Luteolin; Masoprocol; Nanotechnology; Naphthols; Phenol; Phosphatidylcholines; Phosphatidylserines; Rosmarinic Acid; Structure-Activity Relationship

A hyphenated LC-DAD-SPE-NMR setup in combination with on-line radical scavenging detection has been applied for the identification of radical scavenging compounds in extracts of Rhaponticumcarthamoides. After NMR measurements, the pure compounds were infused into a mass spectrometer. The technique enabled selective detection and identification of individual radical scavenging compounds without any prior off-line chromatographic steps. Seven compounds, namely, quercetagetin-7-beta-glucopyranoside (1), quercetagetin-7-(6"-acetyl-beta-glucopyranoside) (3), 6-hydroxykaempferol-7-beta-glucopyranoside (2), 6-methoxykaempferol-3-beta-glucopyranoside (4), 6-hydroxykaempferol-7-(6"-acetyl-beta-glucopyranoside) (5), chlorogenic acid (6), and beta-ecdysone (7), were identified in ethanol or aqueous extracts. Compound 5 is a new natural compound. Its radical scavenging activity was tested against DPPH radical and was found to be weaker than that of the reference antioxidants rosmarinic acid and Trolox.

Topics: Biphenyl Compounds; Chromans; Cinnamates; Depsides; Free Radical Scavengers; Leuzea; Nuclear Magnetic Resonance, Biomolecular; Picrates; Plants, Medicinal; Rosmarinic Acid