Antioxidant Activity of Natural Hydroquinones.

Secondary metabolites derived from hydroquinone are quite rare in nature despite the original simplicity of its structure, especially when compared to other derivatives with which it shares biosynthetic pathways. However, its presence in a prenylated form is somewhat relevant, especially in the marine environment, where it is found in different algae and invertebrates. Sometimes, more complex molecules have also been identified, as in the case of polycyclic diterpenes, such as those possessing an abietane skeleton.

Mutual Influences between Nitric Oxide and Paraoxonase 1.

One of the best consolidated paradigms in vascular pharmacology is that an uncontrolled excess of oxidizing chemical species causes tissue damage and loss of function in the endothelial and subendothelial layers. The fact that high-density lipoproteins play an important role in preventing such an imbalance is integrated into that concept, for which the expression and activity of paraoxonases is certainly crucial. The term paraoxonase (aryldialkyl phosphatase, EC 3.

Paraoxonases: metabolic role and pharmacological projection.

Atherosclerosis is one of the leading causes of death in Western countries, with high-density lipoproteins (HDL) playing an important protective role due to their ability to inhibit oxidation of low-density lipoproteins (LDL), thus relieving vascular subendothelial damage. One of the proteins constituting HDL particles is paraoxonase-1 (PON1), an enzyme able to hydrolyze aryl esters, lactones, and organophosphates. Other closely related paraoxonases are designated as PON2, which is a protein localized inside many different kinds of cells, and PON3, not only present in HDL but also in mitochondria and endoplasmic reticulum, as well.

Influence of Dimerization of Apocynin on Its Effects in Experimental Colitis.

Apocynin has been widely used as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) system and shows promise as an anti-inflammatory drug. Diapocynin, the dimeric product generated by the oxidation of apocynin in the presence of myeloperoxidase (MPO), is supposed to be its active form. In this study, diapocynin has been chemically synthesized and its activity on several inflammatory mediators in LPS-stimulated RAW 264.

Immunmodulatory and Antiproliferative Properties of Rhodiola Species.

The traditional medicines of Asia and Europe have long used various Rhodiola species, which are endemic to the subarctic areas of the northern hemisphere, as tonic, adaptogen, antidepressant, and anti-inflammatory drugs. In order to establish the therapeutic uses of these plants in modern medicine, the pharmacological effects of Rhodiola sp. have been widely studied.

Phenylpropanoid and phenylisoprenoid metabolites from Asteraceae species as inhibitors of protein carbonylation.

Three phenolic antioxidant and anti-inflammatory compounds: 7-methylaromadendrin, isoprenylhydroquinone glucoside, and 3.5-dicaffeoylquinic acid methyl ester, all isolated from Western Mediterranean Asteraceae species, have been studied for their inhibitory activity against protein carbonylation, a harmful post-translational modification of peptide chains associated with degenerative diseases. All compounds have proven to be effective, with 50% inhibitory concentration (IC₅₀) values in the micromolar range, against bovine serum albumin carbonylation caused by hypochlorite, peroxynitrite, and phorbol ester-induced leukocyte oxidative burst.

Phenolic substances from Phagnalon rupestre protect against 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity.

2-isoprenylhydroquinone-1-glucoside (1), 3,5-dicaffeoylquinic acid (2), and 3,5-dicaffeoylquinic acid methyl ester (3), isolated from Phagnalon rupestre, improved the contact hypersensitivity response to 2,4,6-trinitrochlorobenzene in mice. These phenolics reduced ear swelling and IL-1β content by 50% 24 h after challenge; in addition, 2 inhibited tumor necrosis factor-α by 53%. All three compounds also reduced interleukin-2 content by 50% 72 h after challenge.

Inhibition of delayed-type hypersensitivity by Cucurbitacin R through the curbing of lymphocyte proliferation and cytokine expression by means of nuclear factor AT translocation to the nucleus.

Cucurbitacin R is known to exhibit an anti-inflammatory effect in different experimental models of inflammation. In this article, we outline the effect of cucurbitacin R on T lymphocyte proliferation, cytokine production, and nuclear factor activation, as well as its influence on various experimental models of delayed-type hypersensitivity (DTH) in mice. Cucurbitacin R reduced the proliferation of phytohemagglutinin A-stimulated human T lymphocytes (IC(50), 18 microM), modifying the cell cycle, as well as the production of cytokines [interleukin (IL)-2, IL-4, IL-10, and especially interferon-gamma] and the induction of the principal cyclins implicated in the cell cycle (A(1), B(1), D(2), and E).

Interaction of dicaffeoylquinic derivatives with peroxynitrite and other reactive nitrogen species.

Plant phenolic antioxidants, among them catechins and hydroxycinnamoyl conjugates, constitute a well defined class of inhibitors of reactive nitrogen species (RNS). To gain deeper insight in this field, we examined the effects of 3,5-di-O-caffeoylquinic acid (DCA), its methyl ester (DCE) and epigallocatechin gallate (EGCG) in nitrative and oxidative processes. These compounds were found to be strong inhibitors of the nitration of tyrosine residues induced by ONOO- in bovine seroalbumin, with their IC50 values (10-40 microM) notably decreasing in the presence of bicarbonate.

Effects of naturally occurring dihydroflavonols from Inula viscosa on inflammation and enzymes involved in the arachidonic acid metabolism.

The anti-inflammatory properties of three flavanones isolated from Inula viscosa, sakuranetin, 7-O-methylaromadendrin, and 3-acetyl-7-O-methylaromadendrin, have been tested both in vitro and in vivo. Acute inflammation in vivo was induced by means of topical application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to mouse ears or by subcutaneous injection of phospholipase A(2) (PLA(2)) into mouse paws. The test compounds were evaluated in vitro for their effect on both the metabolism of arachidonic acid and on the release and/or activity of enzymes involved in the inflammatory response such as elastase, myeloperoxidase (MPO), and protein kinase C (PKC).

Dihydrocucurbitacin B inhibits delayed type hypersensitivity reactions by suppressing lymphocyte proliferation.

We have studied the effects of dihydrocucurbitacin B, a triterpene isolated from Cayaponia tayuya roots, on different models of delayed type hypersensitivity (DTH) in mice, as well as on T-lymphocyte proliferation and the mediators involved. In experiments with mice, dihydrocucurbitacin B inhibited the inflammatory reactions induced by oxazolone, dinitrofluorobenzene, and sheep red blood cells, reducing both the edema and cell infiltration. Moreover, the analysis of inflamed tissues showed that dihydrocucurbitacin B reduced the presence of the most relevant cytokines implicated in these processes, including interleukin-1 beta, interleukin-4, and tumor necrosis factor-alpha.

Inhibition of pro-inflammatory enzymes by inuviscolide, a sesquiterpene lactone from Inula viscosa.

This work concerns the pharmacological activity of inuviscolide, a sesquiterpenoid from Inula viscosa. It exerts inhibitory effects on elastase, cyclooxygenase 1 and secretory phospholipase A(2). Furthermore, it reduces the skin leukocyte infiltration in a murine model of dermatitis induced by repeated application of 12-O-tetradecanoylphorbol 13-acetate.

Modulation of protein tyrosine nitration and inflammatory mediators by isoprenylhydroquinone glucoside.

The nitration of tyrosine caused by peroxynitrite and other reactive nitrogen species is clearly detrimental for some physiological processes; however, its signalling role is still open to controversy. Among the natural phenolics known for their ability to oppose free tyrosine nitration, isoprenylhydroquinone glucoside is investigated due to its unusual structure, which contains a simple hydroxybenzene alkylated by a hemiterpenoid moiety. This hydroquinone was shown to be an effective inhibitor of peroxynitrite-induced protein tyrosine nitration in 3T3 fibroblasts.

New insight into the inhibition of the inflammatory response to experimental delayed-type hypersensitivity reactions in mice by scropolioside A.

Scropolioside A, an iridoid isolated from Scrophularia auriculata ssp. pseudoauriculata, showed anti-inflammatory properties against different experimental models of delayed-type hypersensitivity. This iridoid reduced the oedema induced by oxazolone by 79% (72 h) at 0.

Inhibition of the pro-inflammatory mediators' production and anti-inflammatory effect of the iridoid scrovalentinoside.

We have studied scrovalentinoside, an iridoid with anti-inflammatory properties isolated from Scrophularia auriculata ssp. pseudoauriculata, as an anti-inflammatory agent in different experimental models of delayed-type hypersensitivity. We found that scrovalentinoside reduced the edema induced by oxazolone at 0.

Protein tyrosine nitration induced by heme/hydrogen peroxide: inhibitory effect of hydroxycinnamoyl conjugates.

The present study was designed to optimize the experimental conditions that govern the heme-catalyzed nitration of protein tyrosine residues by nitrite, and, within this framework, to study the effects of 3,5-dicaffeoylquinic acid and its methyl ester, both of which have been previously reported to be antioxidants and inhibitors of leukocyte functions. Although the presence of hydrogen peroxide is essential in cell-free systems, an excess of this compound was found to be detrimental, so much so that an increase in hemin concentration actually resulted in an inverse effect on the reaction, depending on the levels of fixed hydrogen peroxide. Unlike previous reports on nitrite-induced albumin tyrosine nitration, the optimal pH here was found to be 7.

Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.

Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner.

Cucurbitacin R reduces the inflammation and bone damage associated with adjuvant arthritis in lewis rats by suppression of tumor necrosis factor-alpha in T lymphocytes and macrophages.

The aim of this study was to investigate the effects of cucurbitacin R on an experimental model of adjuvant-induced arthritis in rats. The treatment of arthritic rats with cucurbitacin R (1 mg/kg p.o.

Drugs modulating the biological effects of peroxynitrite and related nitrogen species.

The term "reactive nitrogen species" includes nitrogen monoxide, commonly called nitric oxide, and some other remarkable chemical entities (peroxynitrite, nitrosoperoxycarbonate, etc.) formed mostly from nitrogen monoxide itself in biological environments. Regardless of the specific mechanisms implicated in their effects, however, it is clear that an integrated pharmacological approach to peroxynitrite and related species is only just beginning to take shape.

Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum.

We have studied the effect of 5- O-demethylnobiletin ( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound 1 reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA (2)-induced oedema in mouse paws. The flavone inhibited leukotriene B (4) formation in rat neutrophils and elastase release in human neutrophils, but did not reduce the expression of cyclooxygenase-2 (COX-2) in murine RAW 264.

Dihydrocucurbitacin B, isolated from Cayaponia tayuya, reduces damage in adjuvant-induced arthritis.

23,24-Dihydrocucurbitacin B, from the anti-rheumatic plant Cayaponia tayuya, was tested on arthritis induced by adjuvant to corroborate the anti-inflammatory properties of this plant. Arthritis was induced in Lewis rats; the resulting arthritic rats were then treated with dihydrocucurbitacin B (1 mg/kg orally, daily, 1 week). The effect of dihydrocucurbitacin B on the synthesis, release, and activity of pro-inflammatory enzymes (elastase, cyclooxygenase-2, and nitric oxide synthase-2) as well as its effect on different mediators (tumor necrosis factor-alpha and interleukin-1beta) were determined.

Isoprenylhydroquinone glucoside: a new non-antioxidant inhibitor of peroxynitrite-mediated tyrosine nitration.

Three hydroquinone glucosides and four caffeoylquinic esters were examined for their effect on tyrosine nitration, as well as on the oxidation of dihydrorhodamine (DHR) 123 and cytochrome c(2+) induced by peroxynitrite. All these phenolics, which had previously been characterized as the active principles of the plant Phagnalon rupestre, were fairly active in preventing the oxidation of DHR 123, though inefficient in the cytochrome c test. While their antioxidant potency is associated with the presence of a caffeoyl moiety, not so an obvious chemical character was correlated to a greater activity against nitration of tyrosine.

Anti-inflammatory activity of two cucurbitacins isolated from Cayaponia tayuya roots.

Fractionation of an anti-inflammatory extract from Cayaponia tayuya roots yielded two active compounds, identified as 23,24-dihydrocucurbitacin B (1) and cucurbitacin R (2). Both were evaluated for their anti-inflammatory activity on several experimental models of pain and inflammation. In addition, their cytotoxicity and effects on leukotriene B4 (LTB4) formation were evaluated in rat polymorphonuclear leukocytes.

Anti-inflammatory activities of two flavanones, sigmoidin A and sigmoidin B, from Erythrina sigmoidea.

Two prenylated flavanones isolated from Erythrina sigmoidea Hua (sigmoidin A and sigmoidin B) were studied for their ability to inhibit the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and arachidonic acid metabolism. In addition, the compounds were studied in two experimental models of inflammation induced in mouse ears by 12- O-tetradecanoylphorbol 13-acetate (TPA) and the phospholipase A (2)-induced mouse paw oedema. Both sigmoidins A and B proved to be potent scavengers of the DPPH radical, while the study of the inhibition of arachidonic acid metabolism demonstrated that these same compounds were selective inhibitors of 5-lipoxygenase, with no effect on cyclooxygenase-1 activity.