Anti-acetylcholinesterase, antidiabetic, anti-inflammatory, antityrosinase and antixanthine oxidase activities of Moroccan propolis

Biological properties of Moroccan propolis have been scarcely studied. In the present work, the total phenols and flavonoids from 21 samples of propolis collected in different places of Morocco or 3 supplied in the market were determined, as well as the invitro capacity for inhibiting the activities of acetylcholinesterase, -glucosidase, -amylase, lipoxygenase, tyrosinase, xanthine oxidase and hyaluronidase. The results showed that samples 1 (region Fez-Boulemane, Sefrou city) (IC50=0.065, 0.006, 0.020, 0.050, 0.014mgmL(-1)) and 23 (marketed) (IC50=0.018, 0.002, 0.046, 0.037, 0.008mgmL(-1)) had the best invitro capacity for inhibiting the -amylase, -glucosidase, lipoxygenase, tyrosinase and xanthine oxidase activities, respectively. A negative correlation between IC50 values and concentration of phenols, flavones and flavanones was found. These activities corresponded to the generally higher amounts of phenols and flavonoids. In the same region, propolis samples have dissimilar phenol content and enzyme inhibitory activities

Effects of abasic sites on structural, thermodynamic and kinetic properties of quadruplex structures

Abasic sites represent the most frequent lesion in DNA. Since several events generating abasic sites concern guanines, this damage is particularly important in quadruplex forming G-rich sequences, many of which are believed to be involved in several biological roles. However, the effects of abasic sites in sequences forming quadruplexes have been poorly studied. Here, we investigated the effects of abasic site mimics on structural, thermodynamic and kinetic properties of parallel quadruplexes. Investigation concerned five oligodeoxynucleotides based on the sequence d(TGGGGGT), in which all guanines have been replaced, one at a time, by an abasic site mimic (dS). All sequences preserve their ability to form quadruplexes; however, both spectroscopic and kinetic experiments point to sequence-dependent different effects on the structural flexibility and stability. Sequences d(TSGGGGT) and d(TGGGGST) form quite stable quadruplexes; however, for the other sequences, the introduction of the dS in proximity of the 3′-end decreases the stability more considerably than the 5′-end. Noteworthy, sequence d(TGSGGGT) forms a quadruplex where dS does not hamper the stacking between the G-tetrads adjacent to it. These results strongly argue for the central role of apurinic/apyrimidinic site damages and they encourage the production of further studies to better delineate the consequences of their presence in the biological relevant regions of the genome

Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo

BACKGROUND: Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study. METHODS: We compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation. RESULTS: The in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression. CONCLUSION: This study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies

Regulation of intracellular pH by phospholipase A2 and protein kinase C upon neutrophil adhesion to solid substrata

AbstractAdhesion to solid substrata has been shown to increase intracellular pH (pH(i)) of fibroblasts and of other cells (FEBS Lett. (1988) 234, 449–450; Proc. Natl. Acad. Sci. USA (1989) 86, 4525–4529; J. Biol. Chem. (1990) 265, 1327–1332; Exp. Cell Res. (1992) 200, 211–214; FEBS Lett. (1995) 374,17–20). We have found that the inhibitors of PLA2, 4-bromophenacyl bromide and manoalide, completely blocked the increase of pH(i) and spreading of neutrophils upon adhesion to solid substrata. Inhibition of phospholipase C with neomycin or removal of extracellular Ca2+ affects neither neutrophil spreading nor their pH(i). Inhibition of PKC with H-7 or staurosporin increased pH(i). PMA, an activator of PKC, dramatically decreased pH(i) but did not impair the spreading of neutrophils. The effect of arachidonic acid, a product of PLA2 activity, on neutrophil pH(i) and spreading was similar to that of PMA. H-7, an inhibitor of PKC, partially blocked the effect of arachidonic acid (AA) on pH(i). BW755C, an inhibitor of AA metabolism by cyclooxygenase or lipoxygenase, affected neither the pH(i) nor cell spreading. We propose that the increase of pH(i) upon neutrophil adhesion is mediated by PLA2 activity, while PKC decreased pH(i). AA produced by PLA2 activates PKC, thus forming a feedback regulation of pH(i)

Respiratory burst inhibition in human neutrophils by ultra-low doses of [D-Ala2]methionine enkephalinamide

AbstractAn ultra-low dose (10−14 M) of opioid peptide [D-Ala2]methionine enkephalinamide (DAMEA) is found to exert an inhibitory effect on the production of reactive oxygen species (respiratory burst) in human neutrophils. The validity of this phenomenon has been verified in a series of studies that comprised 30 experiments. The inhibition has proved to be statistically significant (P<0.001). The dose-response dependence of the effect (10−15−10−9 M) followed a characteristic biphasic pattern (with the maximum effect at ultra-low doses). An opioid antagonist, naloxone partially blocks the inhibitory effect, which indicates that the DAMEA action is at least partially mediated by opioid receptors

Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties

AbstractCaffeic 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 μM, it completely blocks production of reactive oxygen species in human neutrophils and the xanthine/xanthine oxidase system

Adhesive interactions of neutrophils and leukotriene synthesis

AbstractCell-substrate and cell-cell adhesion of neutrophils has been found to slow down the calcium ionophore A23187-induced synthesis of 5-lipoxygenase (5-LO) metabolites of arachidonic add. Addition of the exogenous substrate, arachidonic acid (AA), together with A23187, resulted in the enhanced production of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) by adherent neutrophils in comparison with those by the cells in suspension. We observed also the enhanced production of 5-LO metabolites in attached cells when we stimulated the cells by the combined action of phorbol 12-myristate 13-acetate (PMA) and A23187. Thus, the adhesion to solid substrate and to other cells, an important regulatory factor for the activity of many cells, is a powerful regulator of leukotriene production by neutrophils