Antioxidant and neuroprotective effects of synthesized sintenin derivatives

Three series of sintenin derivatives (compounds 1-14) were designed and prepared and their antioxidative and neuroprotective effects were evaluated. The in vitro models of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, chelating ferrous ions, inhibiting the rat brain homogenates lipid peroxidation, and protecting neurons damaged by hydrogen peroxide were employed for bioassays. It was found that sintenin derivatives 4 and 13 showed remarkable antioxidative and neuroprotective activities.     

Neuroprotective effects of (E)-3,4-diacetoxystyryl sulfone and sulfoxide derivatives in vitro models of Parkinson's disease

(E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides have been reported as novel multifunctional neuroprotective agents in previous studies, which as phenolic compounds display antioxidative and antineuroinflammatory properties. To further enhance the neuroprotective effects and study structure-activity relationship of the derivatives, we synthesized their acetylated derivatives, (E)-3,4-diacetoxystyryl sulfones and sulfoxides, and examined their neuroprotective effects in vitro models of Parkinson’s disease. The results indicate that (E)-3,4-diacetoxystyryl sulfones and sulfoxides can significantly inhibit kinds of neuron cell injury induced by toxicities, including 6-OHDA, NO, and H₂O₂. More important, they show higher antineuroinflammatory properties and similar antioxidative properties to corresponding un-acetylated compounds. Thus, we suggest that (E)-3,4-diacetoxystyryl sulfones and sulfoxides may have potential for the treatment of neurodegenerative disorders, especially Parkinson’s disease.     

Quinic acid derivatives from Saussurea triangulata attenuates glutamate-induced neurotoxicity in primary cultured rat cortical cells

The leaves of Saussurea triangulata (Compositae) have been eaten with rice as a wrapping vegetable for preventing neuro-aging. However, the components responsible for the neuroprotective effects of S. triangulata still remain unidentified. In the process of investigating the neuroprotective activity of S. triangulata, we found that a methanol extract of S. triangulata exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. Three quinic acid derivatives were isolated from the n-BuOH fraction of S. triangulata. Among these three quinic acid derivatives, methyl 5-caffeoylquinic acid (3) exhibited significant neuroprotective activities against glutamate-induced toxicity exhibiting cell viability of about 50%, at concentrations ranging from 0.1 μM to 10 μM. Therefore, the neuroprotective effect of S. triangulata might be due to the inhibition of glutamate-induced toxicity by the quinic acid derivatives from S. triangulata.     

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen–Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.     

Occurrence of l-Saccharopine and γ-L-Glutamylglycine in the Mushroom,Agaricus bisporus

Microfolicoumarin (1), a prenylcoumarin from Cedrelopsis microfoliata, was synthesized from 2,4,5-trimethoxybenzaldehyde in five steps. 1 did not show significant antioxidative activity, but the key intermediates, esculetin (3) and 5-prenylesculetin (6), exhibited strong antioxidative activity in both the superoxide-radical and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging models.     

Design,synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors

Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC₅₀?=?1.06, 1.63 and 1.63?µM, respectively). The structure–activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (K_i?=?7.46 and 3.09?µM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi–Sigma interaction and three Pi–Alkyl interactions.     

Serum prolidase activity and oxidative–antioxidative status in patients with developmental dysplasia of the hip and its relationship with radiographic severity

Background: We aimed to investigate serum prolidase activity and to investigate its association with oxidative–antioxidative status in patients with developmental dysplasia of the hip (DDH).

Methods: Oxidative status parameters, including lipid hydroperoxide (LOOH), total oxidant status (TOS), and the oxidative stress index (OSI), and antioxidative status parameters, free sulfhydryl groups (Total –SH), and total antioxidative capacity (TAC), as well as serum prolidase activity were assessed in patients with DDH (n?=?93), and in healthy controls (n?=?82). The severity of dysplasia was evaluated according to the Tonnis grading system.

Results: Serum prolidase activity and the oxidant parameters (LOOH, TOS, and OSI) were significantly higher and the antioxidant parameters (Total –SH and TAC) were significantly lower in patients with DDH compared to the controls (P?P?P?Conclusion: Increased levels of serum prolidase activity, LOOH, TOS, and OSI, and decreased levels of total –SH and TAC, may be associated with DDH, and these parameters may be useful adjunctive tools to assess the severity of DDH.     

Protective effect of Mori Cortex radicis extract against high glucose-induced oxidative stress in PC12 cells

ABSTRACT

This study was undertaken to investigate the neuroprotective effect of an ethanolic extract of Mori Cortex radicis (MCR) against high glucose (HG)-induced oxidative damage in PC12 cells. Cell cytotoxicity was examined using MTT and lactate dehydrogenase assays. To examine the antioxidative effects, intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the activities of antioxidant enzymes were measured. The expressions of apoptosis-associated proteins were assessed. MCR was found to increase the viabilities of HG-induced PC12 cells and to inhibit ROS and MDA production and to promote antioxidative enzyme activities. Furthermore, MCR reduced apoptosis by upregulating p-Akt and Bcl-2/Bax ratio and reducing cytochrome c level. The main flavonoids in MCR were identified by HPLC to be kuwanon G and morusin. These results suggest the antioxidative effects of MCR protect against HG-induced oxidative stress and that MCR has potential therapeutic use for the prevention and treatment of diabetic neuro-degeneration.     

Water-soluble ferulic acid derivatives improve amyloid-β-induced neuronal cell death and dysmnesia through inhibition of amyloid-β aggregation

Ferulic acid (FA) has been reported to exhibit protective effects against amyloid-β (Aβ)-induced neurodegeneration in vitro and in vivo. Recently, we developed two water-soluble FA derivatives: 1-feruloyl glycerol and 1-feruloyl diglycerol. In this study, we examined the neuroprotective effects of these water-soluble FA derivatives on Aβ-induced neurodegeneration both in vitro and in vivo. FA and water-soluble FA derivatives inhibited Aβ aggregation and destabilized pre-aggregated Aβ to a similar extent. Furthermore, water-soluble FA derivatives, as well as FA, inhibited Aβ-induced neuronal cell death in cultured neuronal cells. In in vivo experiments, oral administration of water-soluble FA derivatives to mice improved Aβ-induced dysmnesia assessed by contextual fear conditioning test and protected hippocampal neurons against Aβ-induced neurotoxicity. This study provides useful evidence suggesting that water-soluble FA derivatives are expected to be effective neuroprotective agents.     

Antioxidative Activities of Galloyl Glucopyranosides from the Stem-Bark of Juglans mandshurica

Two phenolics, 1,2,6-trigalloylglucose (1) and 1,2,3,6-tetragalloylglucose (2), isolated from the stem-bark of Juglans mandshurica were evaluated for their antioxidative activities. The results showed that compounds 1 and 2 exhibited strong scavenging activities against 1,1′-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzenthiazoline-6-sulphonic) acid (ABTS^?+), and superoxide radicals (O₂ ^??), and also had a significant inhibitory effect on lipid peroxidation and low-density lipoprotein (LDL) oxidation. The strong superoxide radical scavenging of 1 and 2 resulted from the potential competitive inhibition with xanthine at the active site of xanthine oxidase (OX). In addition, compounds 1 and 2 displayed significant lipoxygenase inhibitory activity, the mode of inhibition also being identified as competitive. In comparison, the antioxidative activities of compounds 1 and 2, together with gallic acid, indicated that the number of galloyl moieties could play an important role in the antioxidative activity.     

NADH-Dependent Glutamat Synthase in Euglena gracilis z

Novel antioxidative phenylpropanoid-substituted tocopherol derivatives, prunusols A and B, were isolated from the leaf wax of Prunus grayana Maxim., and their structures were fully characterized by spectroscopic and synthetic methods. Prunusols A and B were found to be the conjugates of γ-tocopherol and p-coumaric acid, which are diastereoisomers of each other. They showed almost the same antioxidative activity as α-tocopherol in a water/alcohol system measured by thiocyanate and TBA methods.     

A Unique γ-Glutamyltransferase from Fruiting Bodies of Tricholoma shimeji

The extract of terrestrial alga Nostoc commune Vauch. has high antioxidative activity. Our study on N. commune Vauch. resulted in the isolation of two β-ionone derivatives, nostocionone and 3-oxo-β-ionone, together with four indole alkaloids, scytonemin, reduced scytonemin, N-(p-coumaroyl)tryptamine, and N-acetyltryptamine. The structures of the isolated compounds were determined on the basis of 1D and 2D NMR and MS analyses. Among these isolates, nostocionone and reduced scytonemin demonstrated strong antioxidative activities which were assessed by using a β-carotene oxidation assay.     

Turnover of Phospholipids in Bacillus cereus under Various Growth Conditions

As a search for natural antioxidants from plant materials, strong antioxidative activity was observed in leaf waxes extracted from Eucalyptus species. A novel type of antioxidant was isolated from the leaf wax of Eucalyptus globulus and identified as n-tritriacontan-16,18-dione. Antioxidative activities were determined by different methods; a thiocyanate method, a thiobarbituric acid method, a total carbonyl value method and a weighing test. The anti-oxidant showed remarkable antioxidative activity in a water/alcohol system and was more effective than α-tocopherol and BHA; however, it has no antioxidative activity in an oil system.     

In vivo assessment of antidiabetic and antioxidative activity of natural phytochemical isolated from fruit-pulp of Eugenia jambolana in streptozotocin-induced diabetic rats

Objectives: Eugenia jambolana (E. jambolana) is well known for its antidiabetic potential. The aim of the present study was to investigate the antidiabetic and antioxidative effect of an active compound (FIIc) isolated from fruit-pulp of E. jambolana in streptozotocin (45?mg/kg body weight)-induced diabetic rats.

Methods: FIIc was isolated from the crude aqueous extract of fruit-pulp by ion-exchange column chromatography and high-performance column chromatography. Detailed UV, NMR, and IR spectra suggested that FIIc is α-hydroxy succinamic acid. FIIc was orally administered to diabetic rats at a dose of 10, 15, and 20?mg/kg body weight (mg/kg bwt.) to determine its effective dose. Thereafter, effective dose was administered to 8 weeks to determine its antidiabetic and antioxidative activity by estimation of glycemic index, lipid profile, key enzymes of carbohydrate metabolism, and oxidative stress parameters.

Results: Administration of 15?mg/kg dose daily for 8 weeks led to significant (P?P?Discussion: The results demonstrate that FIIc possesses significant antidiabetic and antioxidative activity.     

Chroman amide and nicotinyl amide derivatives: Inhibition of lipid peroxidation and protection against head trauma

A series of chroman amide and nicotinyl amide derivatives was designed and synthesized for the treatment of traumatic and ischemic CNS injury. Five compounds were significantly more potent inhibitors of lipid peroxidation in vitro than the reference antioxidant, trolox (p < 0.01). Quantitative structure activity studies demonstrated that the inhibitory action was related to the ability to donate electrons, charge on hydroxy group and E_LUMO, to scavenging radicals and to the lipophilicity log P, which determines penetration of membrane lipids. ESR study indicated the ability of 12 to scavenge the hydroxyl radicals. The most promising compound, [(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2yl)carbonyl]-3′-(aminoethyl) indole (12), inhibited ex vivo lipid peroxidation in a head injury model and showed potent in vivo neuroprotective efficacy. Improvement of neurological recovery within 1 h of injury (grip test score) by as much as 200% was observed together with significant anti-anoxia activity. Compound 12 was a potent antagonist of methamphetamine-induced hypermotility resulting from dopamine release in the mouse brain. These results support the importance of cerebroprotective radical-scavenging agents for the treatment of traumatic injury and anoxia as well as provide additional evidence for the role of oxygen radicals and dopamine in brain damage.     

Synthesis and Biological Activity of O,O-Dialkyl S-(5-Aryl-l,3,4-oxadiazol-2(3H)-on-3-yl)methyl Phosphorothioates and Phosphorodithioates

Some phosphorus derivatives of oxadiazoles were synthesized to seek insecticidal lead compounds. The l,3,4-oxadiazol-2-ones were converted via the N-methylol derivatives to the corresponding N-chloromethyl derivatives. From these derivatives a variety of O,O-dimethyl phosphorodithioates 4, O,O-dimethyl phosphorothioates 5 and O,O-di-i-propyl phosphorothioates 6 were prepared.

These phosphorus derivatives were examined for insecticidal activity towards houseflies and for anti-acetylcholinesterase (anti-AChE) activity using the housefly heads as an enzyme source. Most of the compounds 4 and 5 showed contact toxicity as high as the analogous methidathion insecticides, which appeared to correlate with the strong anti-AChE activity. On the other hand, all the compounds 6 showed a high activity in AChE inhibition but only a poor insecticidal activity.     

New Pyrano-4H-benzo[g]chromene-5,10-diones with Antiparasitic and Antioxidant Activities

New pyranonaphthoquinone derivatives were synthesized and investigated for their activity against Trypanosoma brucei, Leishmania major, and Toxoplasma gondii parasites. The pentafluorophenyl derivative was efficacious against T. brucei with single digit micromolar EC₅₀ values and against T. gondii with even sub-micromolar values. The 3-chloro-4,5-dimethoxyphenyl derivative showed an activity against amastigotes of Leishmania major parasites comparable to that of amphotericin B. In addition, antioxidant activities were observed for the bromophenyl derivatives, and their redox behavior was studied by cyclovoltammetry. Anti-parasitic and antioxidative activities of the new naphthoquinone derivatives appear uncorrelated.     

A Rennin-like Enzyme from Penicillium expansum

dl-(1,3/2)-3-Acetamido-1,2-di-O-benzylcyclohex-4-enediol (IIIa) and dl-(1,3/4)-1-acetamido-3,4-di-O-benzylcyclohex-5-enediol (IIIb) were synthesized from dl-trans-1,2-di-O-benzylcyclohex-3-enediol (I) via the corresponding azide derivatives (IIa-b) prepared by bromination and subsequent treatment with sodium azide in N,N-dimethylformamide. Compounds (IIIa and IIIb) were converted into a variety of deoxyinosamine and deoxyinosadiamine derivatives via epoxides (VIII and IX) or by cis-hydroxylation with osmium tetroxide. Hexaacetyl-rac-inosamine-1 (XVIIIc) was synthesized from dl-(1,3,4/2,5)-3-acetamido-1,2-di-O-benzyl-5-bromocyclohexanetriol (VIa) via conduramine derivatives (XVIIa-c). Conformationai analysis of partially O-benzylated aminocyclitol derivatives were studied by means of NMR spectroscopy.     

The acute phase protein haptoglobin and its relation to oxidative status in piglets undergoing weaning-induced stress

Abstract

Haptoglobin (Hp) prevents the hemoglobin driven generation of hydroxyl radicals and lipid peroxides. Hp can reduce the neutrophil respiratory burst and is an antioxidative molecule in its own right. We aimed to evaluate Hp concentrations, oxidative stress and antioxidative capacity in blood during weaning and to characterise potential relationships between these parameters. Two batches of 10 piglets each (2 trials) weaned at the age of 27–30 days were fed a starter feed mix ad libitum. Blood samples were taken 1 week before weaning and at weekly intervals thereafter. Oxidative stress was monitored via the D-ROM^® system, antioxidative capacity was measured with the TEAC assay and Hp concentrations were measured by ELISA. Neutrophil phagocytic activity and oxidative burst were examined via flow-cytometry. Body weights were recorded weekly. Hp concentrations were increased in both trials post-weaning (P < 0.01); oxidative stress and oxidative burst were elevated in trial I (P < 0.005). In trial I, Hp and ROM values returned to baseline levels at 6 weeks post-weaning. The piglets in trial II showed respiratory symptoms and maintained elevated Hp concentrations. ROM values and Hp were related (r = 0.58; P < 0.01). Hp and body weight gain were inversely related post-weaning.     

Dopamine Promotes the Survival of Embryonic Striatal Cells: Involvement of Superoxide and Endogenous NADPH Oxidase

The dopaminergic system appears early in mammalian brain development, and a neurodevelopmental role for dopamine (DA) has been suggested. In the present study, we found that DA markedly promoted the survival of embryonic striatal cells in cultures. The failure of DA receptor antagonists to block this survival-promoting effect and the capability of S-apomorphine, which is devoid of DA receptor agonist activity but possesses antioxidative activity as R-apomorphine and DA, to completely mimic this effect suggested that DA receptor activation was not required in the survival-promoting effect elicited by DA, and its antioxidative activity might be involved. Moreover, it was found that mRNA of NADPH oxidase was expressed in the embryonic striatum. Furthermore, DPI or apocynin, NADPH oxidase inhibitors, promoted the survival of embryonic striatal cells. Addition of either DA or DPI into striatal cell cultures decreased the superoxide level. These results indicate that the mechanisms underlying the neuroprotective effects of DA were likely associated with its antioxidative activity. NADPH oxidase might contribute, at least in part, to ROS generation.