Lipoxygenase Inhibitor

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Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells

Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells

Abstract: Leukocyte adhesion contributes to perfusion abnormalities and tissue damage during trauma, shock or overwhelming infl ammation. This study was performed to determine whether the lipoxygenase inhibitor phenidone and derivatives decrease the expression of adhe- sion molecules on tumor necrosis factor- α (TNF- α ) stimulated endothelial cells and attenuate leukocyte-endothelial interactions under fl ow in vitro. TNF- α stimulated human umbilical venous endothelial cells (HUVECs) were incubated with phenidone, 4-methyl-phenidone, 4-4-dimethyl-phenidone, 5-methyl-phenidone, 5-phenyl-phenidone, and 5-methyl-1,(2,5-di- chloro-phenyl)-3-pyrazolidone. We tested the inhibition of adhesion molecule expression at different inhibitor concentrations before, during, and after the stimulation of HUVECs. The inhibition of endothelial cell expression on HUVECs was measured by fl ow cytometry. Roll- ing and fi rm adhesion of leukocytes to pretreated endothelium was examined in a parallel plate fl ow chamber. Phenidone inhibited the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVECs when added prior to HUVEC stimulation. The inhibitory effect of phenidone was still observed when added simultaneously, but not when added after HUVEC stimulation. 4-4-dimethyl-phenidone and 5-phenyl-phenidone inhibited the expression of adhesion molecules more effectively than phenidone. The attenuation of leukocyte rolling under fl ow conditions was also signifi cantly more effective with 4-4-dimethyl-phenidone than with phenidone. Lipoxygenase inhibitors might be of therapeutically interest for the treatment of overwhelming systemic infl ammation during shock, trauma, and sepsis.

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5 LIPOXYGENASE INHIBITOR (ZILEUTON) PRODUCES ANTI DEPRESSION EFFECT IN STRESS INDUCE CRS MICE MODEL

5 LIPOXYGENASE INHIBITOR (ZILEUTON) PRODUCES ANTI DEPRESSION EFFECT IN STRESS INDUCE CRS MICE MODEL

Result: Stress induces CRS model guide to the significant depressive-like behavior of the mice in behavioral tests which was united by adverse changes at the cellular/molecular level responsible for regulation of inflammatory and apoptotic processes. CRS triggered Microglial over activation in the DG of the hippocampus, which was successfully inhibited by Zileuton post-treatment at the dose of 100mg/kg than 50mg/kg. Level of TNF-α, IL- 1β, nuclear NF-κB p65, Bax, and cleaved Caspase-3 was high and Bcl-2 expression was low in the stress induce CRS -treated mice which were found to be opposite in the Zileuton (100mg/kg). However, the dose of 50mg/kg less to mimic the effects as exhibited more by the 100mg/kg dose of Zileuton. Conclusion: It can be concluded that selective 5-lipoxygenase inhibitor Zileuton can efficiently inhibit the depressive-like behavior/activity in CRS- induced depressive mouse model. The study is the first to show the role of 5-lipoxygenase enzyme in and Chronic Restraint Stress (CRS)-induced mice models of stress, anxiety or depression.

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The 1,4 benzoquinone-featured 5-lipoxygenase inhibitor RF-Id induces apoptotic death through downregulation of IAPs in human glioblastoma cells

The 1,4 benzoquinone-featured 5-lipoxygenase inhibitor RF-Id induces apoptotic death through downregulation of IAPs in human glioblastoma cells

In this context, the pro-inflammatory microenviroment in various human brain tumors is characterized by high ex- pression of 5-Lipoxygenases (5-LOX) [8], a versatile class of oxidative enzymes involved in arachidonic acid metabolism, that promote the proliferation of glioma cells [9 – 12]. In addition, is well recognized that the inhibitors of 5-LOX can activate Caspase-3 inducing glioma cell apoptosis, sug- gesting that 5-LOX can participate in the survival of glioma cells [13]. In this context NDGA, a natural 5-LOX inhibitor, and its methylated derivative, terameprocol, exhibited anti- cancer activity; moreover, terameprocol is a global tran- scription inhibitor that affects cell division, apoptosis, drug resistance, hypoxia responsive genes, and radiation resist- ance in hypoxia. Previous research indicated terameprocol as a drug that could be safely combined with radiation in newly diagnosed high-grade glioma [14].

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EFFECTS AND UNDERLYING MECHANISM OF 5 LIPOXYGENASE INHIBITOR (ZILEUTON) ON MICE DEPRESSIVE LIKE BEHAVIOR

EFFECTS AND UNDERLYING MECHANISM OF 5 LIPOXYGENASE INHIBITOR (ZILEUTON) ON MICE DEPRESSIVE LIKE BEHAVIOR

Results: Zileuton (50/100 mg/kg) administration improved the performance of the mice in the behavioral experiments (p<0.05 or 0.01). Immunohistochemistry detection of Iba1+ revealed over activation of microglial cells in the corticosteroid-treated mice which was suppressed by the zileuton (50 or 100 mg/kg [p<0.05 or 0.01]). Through Western blotting tests, it had been found that CORT (i.p.) administration led to the increment of the protein 5-Lipoxygenase in the mouse hippocampus associated with neuroinflammation, which was decreased significantly by zileuton (p<0.05 or 0.01). Level of tumor necrosis factor-alpha, interleukin-1 beta, nuclear factor kappa B p65 protein (for neuroinflammation), Bax, and cleaved caspase-3 and TUNEL assay increased, and Bcl-2 expression decreased in the CORT-induced depressive mice. These were significantly reversed by zileuton (50 or 100 mg/kg [p<0.05 or 0.01]).

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Resistance to type 1 diabetes induction in 12 lipoxygenase knockout mice

Resistance to type 1 diabetes induction in 12 lipoxygenase knockout mice

Several studies also have addressed the question of whether lipoxygenase inhibitors can prevent pancreatic β-cell death. Zhou and colleagues recently demonstrated that thapsigargin-induced apoptosis in the MIN6 pan- creatic β-cell line was significantly attenuated by lipoxy- genase inhibitors. Furthermore, direct 12-HETE applica- tion in MIN6 cells reproduced the decrease in cell viability seen with thapsigargin (21). Earlier work by Rabi- novitch and colleagues demonstrated that nordihy- droguaiaretic acid, a lipoxygenase inhibitor, protected rat islets from cytokine-induced destruction (11). Others have demonstrated that lipoxygenase pathway products are activated in inflammatory disease states like inflam- matory bowel disease (22), neuronal cells undergoing apoptosis (8), and human monocyte-mediated LDL oxi- dation (23). Therefore, lipoxygenase product generation may participate in a variety of inflammatory conditions. Evidence also exists that lipoxygenase pathway prod- ucts have a role in NO production. Kolb and colleagues demonstrated that nordihydroguaiaretic acid, a prefer- ential lipoxygenase inhibitor, inhibited LPS-stimulated NO production in cultured macrophages in a dose- dependent fashion (24, 25). Our data are consistent with this report in that stimulated macrophages from 12-LO KO mice generated only 50% of the NO seen in similarly treated C57BL/6 macrophages. In contrast, AA metabolism does not seem to affect the production of superoxide by macrophages (15).

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Disruption of the 12/15 lipoxygenase gene diminishes atherosclerosis in apo E–deficient mice

Disruption of the 12/15 lipoxygenase gene diminishes atherosclerosis in apo E–deficient mice

A study of overexpression of 15-lipoxygenase in rabbit iliac arteries indicated that the enzyme might promote atherogenesis (56). The occurrence of oxLDL epitopes was demonstrated in the transfected areas as compared with the contralateral sham-transfected iliac artery (56). Furthermore, in 2 recent publications, it was found that a 15-lipoxygenase inhibitor, PD146176, attenuated the progression of atherosclerosis and monocyte-macro- phage enrichment of lesions in hypercholesterolemic rab- bits in the absence of changes in plasma total or lipopro- tein cholesterol (42, 43), although there was no direct proof of enzyme inhibition in vivo. However, in another study, a different result was found when transgenic rab- bits were generated that overexpressed 15-lipoxygenase in macrophages under control of a lysozyme promoter. These rabbits appeared to develop less atherosclerosis in 2 of 3 experiments (44). The reasons for the differences among these studies are not clear at present.

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In vivo action of 15 lipoxygenase in early stages of human atherogenesis

In vivo action of 15 lipoxygenase in early stages of human atherogenesis

In addition to the results presented here several lines of ex- perimental evidence obtained in different laboratories suggest a patho-physiological role of the 15-lipoxygenase in atherogen- esis. ( a ) The 15-lipoxygenase is expressed in foamy macro- phages (10, 11) as well as in certain types of smooth muscle cells (26) of atherosclerotic lesions. Because the enzyme is not expressed in the normal human arterial wall (10) nor in mac- rophage precursor cells (27) there must be a specific induction of the 15-lipoxygenase during atherogenesis. ( b ) The in vivo activity of the 15-lipoxygenase appears to coincide in time with the onset of lipid deposition in the vessel wall in cholesterol fed rabbits (15). ( c ) Somatic gene transfer of the 15-lipoxygen- ase to a rabbit iliac artery led to the appearance of oxidized LDL epitopes in the transfected areas (28). In contrast, in the contralateral iliac artery that was mock transfected such epitopes were not detected. ( d ) A 15-lipoxygenase inhibitor which lacks antioxidative properties appears to inhibit the de- velopment of atherosclerotic lesions in cholesterol fed rabbits (29). Although these data suggest a role of the enzyme in atherogenesis the molecular mechanism of its action is unclear. Since the 15-lipoxygenase in vitro is capable of oxidizing LDL to an atherogenic form (14, 22) and because fibroblasts transfected with the 15-lipoxygenase cDNA exhibit a higher LDL oxidizing capability than mock-transfected cells (30) one may conclude that the enzyme in vivo may be involved in LDL oxidation. There are several hypothesis to explain how an in- tracellular lipoxygenase can oxidize extracellular LDL (30, 31) but additional experimentation is needed to verify them. On the other hand, initiation of extracellular LDL oxidation may not be the only and, most probably, not even the major action of the enzyme during atherogenesis. It might be possible that the 15-lipoxygenase is induced in foam cells as a part of a lipid metabolizing cascade designed to prevent intracellular lipid deposition (32). Thus, for further mechanistic studies even an antiatherogenic action of the 15-lipoxygenase may be consid- ered (32, 33). In fact, transgenic rabbits which overexpress the Figure 2. Enantiomer separation of 13-HODE isolated from young

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Role of lipoxygenase products in murine pulmonary granuloma formation

Role of lipoxygenase products in murine pulmonary granuloma formation

Various arachidonic acid (AA) metabolites are known to regulate immune cell function(s) and dictate the progression of both acute and chronic inflammatory reactions. Using a model of Schistosoma mansoni egg-induced hypersensitivity granulomas, we have delineated the in vivo effects of inhibitors of cyclooxygenase (CO) and lipoxygenase (LO) pathways on granuloma development and granuloma macrophage I-region-associated (Ia) antigen expression. In addition, by high performance liquid chromatography (HPLC) we have profiled the metabolism of AA by macrophages that are isolated from granulomatous foci, and have biochemically characterized the in vitro specificity and activity of selected CO and LO inhibitors. The development of hypersensitivity-type pulmonary granulomas in mice was dramatically suppressed by inhibitors with anti-LO activity (nordihydroguairetic acid (NDGA), nafazatrom, and BW755c) in a dose-dependent manner, while indomethacin, which is primarily CO-selective, had no significant effect. Furthermore, NDGA and nafazatrom profoundly arrested the normal progression of preformed granulomatous lesions. The inhibitors of the LO pathway also suppressed the in vivo kinetics of Ia antigen expression by granuloma macrophages. In contrast, indomethacin augmented Ia-antigen expression. The major AA metabolites that were synthesized by the granuloma

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The impairment of endothelium-dependent relaxations in isolated rabbit aorta and coronary arteries by low-density lipoproteins and oxidised fatty acids

The impairment of endothelium-dependent relaxations in isolated rabbit aorta and coronary arteries by low-density lipoproteins and oxidised fatty acids

protective role in the vessel wall since it has been identified as a platelet chemorepellant factor produced intracellularly by endothelial cells (Buchanan et al, 1985b) and it has been shown to increase prostacyclin production by endothelial cells (Setty et al, 1987). Furthermore, 13-HODE levels in atherosclerotic rabbit aorta and plasma linoleic acid levels in humans have been found to have an inverse correlation with the degree o f fatty streaks and the risk o f coronary heart disease (Wood et al, 1987; De Meyer et al, 1991). However, other studies have demonstrated increased levels o f linoleic acid-derived hydroperoxides in atherosclerotic lesions and noted a positive correlation between the concentrations o f these products and the degree o f atherosclerosis (Harland et al, 1971; Yalcien et al, 1989). It is possible that 13-HODE is produced from linoleic acid by the increased 15- lipoxygenase activity in vascular tissues as a protective response to hypercholesterolaemia (Simon et al, 1989a). However, 15-HETE was found to be the most abundant lipoxygenase-derived product formed in aortae from atherosclerotic rabbits with more severe lesions (Henriksson et al, 1985; Simon et a/., 1989b). During early fatty streak formation an increased synthesis o f prostacyclin has been demonstrated in endothelial cells, possibly due to the presence o f 13-HODE whereas synthesis o f prostacyclin by endothelial cells is suppressed as the disease progresses (Beetens et al,

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Antioxidant and Lipoxygenase Inhibitory Activity of the Kino of Eucalyptus citriodora

Antioxidant and Lipoxygenase Inhibitory Activity of the Kino of Eucalyptus citriodora

In the present study, antioxidant activity, total phenolic and flavonoid content, and 15-lipoxygenase inhibitory activity of ethanol extract and its ethyl acetate, n-butanol and aqueous fractions of Eucalyptus citriodora kino were evaluated. The antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) methods. The IC 50 values of the ethanol extract were 5.11±0.13, 2.72±0.08 and 25.86±1.81 μg/ml in the 2,2-diphenyl-1-picrylhydrazyl, 2,2’-azino-bis(3-ethylbenzothiazoline- 6-sulfonic acid) methods and the 15-lipoxugenase assay, respectively. Total phenolic and flavonoid content of the ethanol extract were 490.77±1.95 mg catechin equivalents/g and 21.81±0.23 mg quercetin equivalents/g, respectively. Solvent partition of the ethanol extract yielded ethyl acetate, n-butanol and aqueous fractions. Among the three fractions, the ethyl acetate fraction showed the highest total phenolic and flavonoid contents, which were 575.87±3.92 mg catechin equivalents/g and 34.57±0.30 mg quercetin equivalents/g, respectively. This fraction also showed the strongest free radical scavenging activity in the two methods used as well as inhibitory activity against 15-lipoxygenase, with IC 50 values of 4.67±0.09, 2.57±0.06 and 14.67±0.93 μg/ml, respectively. These findings revealed that high antioxidant and lipoxygenase inhibitory activity of Eucalyptus citriodora kino might be due to high phenolic and flavonoid content. These results showed that Eucalyptus citriodora kino could be a potential source of natural antioxidants and lipoxygenase inhibitors which could be used to prevent free radical and lipoxygenase mediated diseases.

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Lipoxygenase contributes to the oxidation of lipids in human atherosclerotic plaques

Lipoxygenase contributes to the oxidation of lipids in human atherosclerotic plaques

Oxidized LDL is present in human atherosclerotic lesions, but the mechanisms responsible for oxidation in vivo have not been definitively demonstrated. Circumstantial evidence has implicated the enzyme 15-lipoxygenase as a contributor to the formation of oxidized lipids in this disease. To assess whether oxidized lipids are indeed formed by the action of 15- lipoxygenase on polyunsaturated fatty acids (PUFAs) in vivo, we have used a sensitive and specific method (chiral phase HPLC) to analyze the lipid oxidation products present in human atherosclerotic lesions. Human 15-lipoxygenase is an omega-6 lipoxygenase that has previously been shown to oxidize esterified PUFA in a stereospecific manner, forming predominantly cholesteryl hydroperoxy-octadecadienoate (13(S)-HPODE) from cholesteryl linoleate substrate in LDL. This property allows its activity to be distinguished from

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In-Vitro Anti-inflammatory Activity Evaluation of the Latex Protease of Holostemma Ada-Kodien Schult

In-Vitro Anti-inflammatory Activity Evaluation of the Latex Protease of Holostemma Ada-Kodien Schult

The anti-inflammatory effects of H. ada-kodien latex protease (HA protease) on the production of leukotrienes were estimated by inhibition of lipoxygenase activity. Results are shown in the Table.2. The HA protease showed good 5-lipoxygenase inhibitory activity when compared to control and standard. These activities are due to the presence of flavonoids, steroids and terpenoids which act as free radical scavenger or acting possibly as primary oxidant thereby inhibiting inflammation.The results of the study indicated that inhibitory effect of each plant extract on enzymes were dose dependent.

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PHYTOCHEMICAL ANALYSIS AND ANTI-INFLAMMATORY ACTIVITY OF MEDICINAL PLANT AQUEOUS AND ETHANOLIC EXTRACT OF BOERHAAVIA DIFFUSA LEAVES EXTRACTS

PHYTOCHEMICAL ANALYSIS AND ANTI-INFLAMMATORY ACTIVITY OF MEDICINAL PLANT AQUEOUS AND ETHANOLIC EXTRACT OF BOERHAAVIA DIFFUSA LEAVES EXTRACTS

inhibitory action. Heat induced haemolysis of erythrocyte was significantly 50% of inhibited atthe concentration of 300.47±2.57 and 238.97±2.03 μg/ml for aqueous and ethanol extract, respectively. Hypotonicity induced haemolysis and lipoxygenase activity were significantly 50% inhibited at the concentrationof309.87±2.69 and300.94±1.77μg/ml, respectively by the aqueous extract. Ethanol extract showed 50% of inhibition of hypotonicity induced haemolysis and lipoxygenase activity was found to be 205.94±2.07 and259.34±2.33μg/ml, respectively. The results obtained in the present study indicate that ethanol extracts of B. diffusa leaves can be a potential source of anti-inflammatory agents compared than aqueous extract.

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Purification and properties of lipoxygenase from wheat seedlings infected by Fusarium graminearum and treated by salicylic acid

Purification and properties of lipoxygenase from wheat seedlings infected by Fusarium graminearum and treated by salicylic acid

Sweden) and Sepharose CL­6B ion­exchange chro­ matography (Pharmacia, Sweden). Column chroma­ tography of lipoxygenase was performed with the help of the equipment of the firm LKB (Sweden), using a low­temperature cabinet (Combicoldrac II), peristaltic pump (Microperpex), ultraviolet detec­ tor with a flow­type cuvette (Uvicord S), collec­ tor of fractions (Ultrorac II), columns 2.6×60 cm, 1.6×95 cm (for G­100), 1.6×70 cm (for DEАE­ Sepharose CL­6B) at 4 °С. Treatment of the Sepha­ dex G­100, ion exchanger DEAE­Sepharose CL­6B was performed following standard methods [7, 8]. The enzyme activity was determined spectrophoto­ metrically by the reaction of fermentative formation of fatty acid hydroperoxides, recorded at 234 nm. A mixture of fatty acids isolated from walnut kernels was used as a substrate. The content of linoleic acid in the mixture was 67%. Concentration of the acid in the mixture was 2.8 mM. The extinction change by 0.01 for 1 min was taken as the unit of lipoxygenase activity. The total protein content in the extract was determined by the Lowry method [10]. The isolated lipoxygenase was determined by the method of ana­ lytical electrophoresis in PAAG in the alkali buffer system at pH 8.3, using a specific oxidation reaction of linoleic acid in the presence of starch and potas­ sium iodide [11, 12]. To reveal the zone of lipoxy­ genase location in gels we used the method by Heil with co­authors [13], based on formation of stained iodine­starch complex in the presence of potassium iodide and linoleic acid hydroperoxides. This in mind soluble starch was introduced before polym­ erization in gel to concentration of 1%; electropho­ resis being finished, gel was incubated for 30­min in 0.5­1.0% solution of sodium salt of linoleic acid. Then the gel, thoroughly washed in distilled water, was placed into mixture­develo per which consisted of 100 ml of 7% acetic acid and 5 ml of freshly pre­ pared saturated solution of KI. The appearance of brown­violet stripes on the yellow background of the gel evidenced for availability of lipoxygenase isoforms.

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Formulation and evaluation of embelin emulgel for topical delivery

Formulation and evaluation of embelin emulgel for topical delivery

Background: Embelin is an isolated compound from Embelia ribes and well known for its potent antioxidant and anti-inflammatory properties. However, so far, embelin has not been explored into a topical dosage form due to its hydrophobic nature. Emulgel is a recently developed formulation and emerged as a promising topical delivery system for the delivery of hydrophobic drugs. Aim: The aim of the study to formulate emulgel of embelin and tested for its antioxidant and anti-inflammatory properties. Materials and Methods: The emulsion was prepared and incorporated in a gel base. The formulations were evaluated for physicochemical properties and tested for in vitro antioxidant activity using 2, 2-Diphenyl-1-picrylhydrazyl method. The formulated emulgels were also tested for inhibition of albumin denaturation and lipoxygenase inhibition to evaluate its in vitro anti-inflammatory activity. Results and Discussion: Both the formulated Emulgels (F1 and F2) were looks a purple creamy with a smooth homogeneous texture and glossy appearance. The formulated embelin emulgel showed potent antioxidant and moderate anti-inflammatory properties that is water soluble gel. Conclusion: This embelin emulgel will be further developed into a commercial standard and tested for in vivo studies to confirm its anti-inflammatory properties.

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Journal of Applied Pharmaceutical Science

Journal of Applied Pharmaceutical Science

genital apparatus inflammation, in the treatment of malaria (Nacoulma, 1996). Despite the widespread use of species belonging to the amaranthaceae’s family, scientific literature provide little data on the biological potential of the extract/fraction of pandiaka angustifolia. In the vision to bring our modest contribution to Burkina Faso’s traditional medicine, the aim of the present study was to evaluate and compare phenolic content, the antioxidant activities, the lipoxygenase and xanthine oxidase inhibition potentials of five fractions and the hydroacetonic macerate of P. angustifolia.

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Systems pharmacology based approach to investigate the in vivo therapeutic efficacy of Albizia lebbeck (L ) in experimental model of Parkinson’s disease

Systems pharmacology based approach to investigate the in vivo therapeutic efficacy of Albizia lebbeck (L ) in experimental model of Parkinson’s disease

ADRA2B: Alpha-2B adrenergic receptor; ADRA2C: Alpha-2C adrenergic receptor; AKR1A1: Alcohol dehydrogenase [NADP(+)]; AKR1B1: Aldo-keto reductase family 1 member B1; AKR1B10: Aldo-keto reductase family 1 member B10; Akt: Protein kinase B; ALE 100: 100 mg/kg treatment control; ALE 200: 200 mg/kg treatment control; ALE 300: 300 mg/kg treatment control; ALE: Albizia lebbeck (L.) extract; ALOX12: Arachidonate 12- lipoxygenase, 12S-type; ALOX12B: Arachidonate 12-lipoxygenase, 12R-type; ALOX15: Arachidonate 15-lipoxygenase; ALOX15B: Arachidonate 15- lipoxygenase B; ALOX5: Arachidonate 5-lipoxygenase; AOX1: Aldehyde oxidase; AR: Androgen receptor; BT: Tissue homogenate of brain; CA1: Carbonic anhydrase 1; CA12: Carbonic anhydrase 12; CA13: Carbonic anhydrase 13; CA14: Carbonic anhydrase 14; CA2: Carbonic anhydrase 2; CA3: Carbonic anhydrase 3; CA4: Carbonic anhydrase 4; CA5A: Carbonic anhydrase 5A; CA5B: Carbonic anhydrase 5B; CA6: Carbonic anhydrase 6; CA7: Carbonic anhydrase 7; CA9: Carbonic anhydrase 9; CAT: Catalase; CDC25A: M-phase inducer phosphatase 1; CDC25B: M-phase inducer phosphatase 2; CDK4: Cyclin-dependent kinase 4; CDK6: Cyclin-dependent kinase 6; cGMP: Cyclic guanosine monophosphate; CHRM1: Muscarinic acetylcholine receptor M1; CHRM2: Muscarinic acetylcholine receptor M2; CHRM4: Muscarinic acetylcholine receptor M4; CHRM5: Muscarinic acetylcholine receptor M5; CSF1R: Macrophage colony-stimulating factor 1 receptor; C-T network: Compound - Target network; CYP17A1: Steroid 17- alpha-hydroxylase/17,20 lyase; CYP19A1: Cytochrome P450 19A1; CYP1A2: Cytochrome P450 1A2; CYP1B1: Cytochrome P450 1B1; CYP2C19: Cytochrome P450 2C19; CYP51A1: Lanosterol 14-alpha demethy- lase; DF: Dilution factor; DNA: Deoxyribonucleic acid; DTNB: 5,5 ′ -Dithiobis-(2- nitrobenzoic acid); EGFR: Epidermal growth factor receptor; ERBB2: Receptor tyrosine-protein kinase erbB-2; ERBB4: ERBB4 intracellular domain; ESR1: Estrogen receptor; ESR2: Estrogen receptor beta; FGFR1: Fibroblast

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Antioxidant and anticancer activities of polyphenolic compounds from three Acanthaceae medicinal species from Burkina Faso

Antioxidant and anticancer activities of polyphenolic compounds from three Acanthaceae medicinal species from Burkina Faso

Lipoxygenase inhibiting activity of plant extracts with linoleic acid as a substrate was measured with a UV/visible light spectrophotometer as described by Malterud and adapted by Compaoré & al. [17]. Extracts were screened for Lipoxygenase inhibitory activity at a final concentration of 50μg/mL. The mixture assay consisted of 150 μL of phosphate borate buffer (1/15 M, pH 7.5), 50 μL of extract solution (1mg/mL) and 50 μL of enzyme solution (0.28 U/mL in phosphate borate). The reaction was initiated by adding 250 μL of substrate solution (0.15 mM in water). Enzymatic kinetic was recorded at 234 nm for 02 min. Negative control was prepared and contained 1% methanol solution without extract solution. All experiments were performed in triplicate. Lipoxygenase inhibitory activity was expressed as the percentage inhibition of Lipoxygenase, calculated as (%) inhibition following equation: (%) inhibition = (A - B/A) 100, where A is the change in absorbance of the assay without the plants extracts and B is the change in absorbance of the assay with the plants extracts. Acetylcholinesterase (AChE) inhibition assay

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A RARE AND SEVERE ICHTHYOSIS OF NEONATES -HARLEQUIN ICHTHYOSIS

A RARE AND SEVERE ICHTHYOSIS OF NEONATES -HARLEQUIN ICHTHYOSIS

.The known causative molecules underlying ichthyosis include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and stero- id sulfatase, all of which are thought to be related to the intercellular lipid layers.ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules and a loss of ABCA12 function leads to defective lipid transport in the keratinocytes, resulting in the most severe, harlequin ichthyosis pheno- type (3,5) .Other causative molecules for ichthyoses are transglutaminase 1, keratins and filag- grin.Harlequin ichthyosis is a severe genetic dis- order that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies.The underlying genetic abnormality in harlequin ichthyosis is a mutation in the lipid-transporter gene ABCA12 on chromosome 2 (6) . In this re- view we are providing the data regarding history,

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Genetic variation in the leukotriene pathway is associated with myocardial infarction in the Chinese population

Genetic variation in the leukotriene pathway is associated with myocardial infarction in the Chinese population

Background: Genetic variation in the genes ALOX5 (arachidonate 5-lipoxygenase), ALOX5AP (arachidonate 5- lipoxygenase-activating protein) and LTA4H (leukotriene A4 hydrolase) has previously been shown to contribute to the risk of MI (myocardial infarction) in Caucasian and African American populations. All genes encode proteins playing a role in the synthesis of the pro-inflammatory leukotriene B mediators, possibly providing a link between MI and inflammation. The aim of the present study was to investigate whether these associations could be confirmed in the study of China MI patients. The study included 401 Han Chinese MI patients and 409 controls. Six tag single nucleotide polymorphisms (SNPs) — ALOX5 rs12762303 and rs12264801, ALOX5AP rs10507391, LTA4H rs2072512, rs2540487 and rs2540477 — were selected. SNP genotyping was performed by an improved multiplex ligation detection reaction assay. Results: The rs2540487 genotype was associated with the risk of MI in overdominant model ( P = 0.008). rs12762303 and rs10507391 SNPs were significantly associated with lipid levels in MI patients ( P < 0.006 – 0.008). Several SNPs interacted with alcohol consumption, cigarette smoking, and hypertension to modify TC, TG, LDL-C and CRE levels, and the risk of MI ( P < 0.0017 for all). No association between the SNPs of LT pathway and susceptibility to MI was found ( P > 0.05 for all).

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