Anticholinesterse and antioxidant investigations of crude extracts,subsequent fractions,saponins and flavonoids of atriplex laciniata L.: potential effectiveness in Alzheimer’s and other neurological disorders

Background

Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer’s and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H₂O₂ free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman’s assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively.

Results

In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC₅₀ for these fractions were 33, 83 and 82 μg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC₅₀ of 30, 190 and 70 μg/ml respectively. further, H₂O₂ percent scavenging was highly appraised in Al.FLVF (91.29 ± 0.53, IC₅₀ 75), Al.SPF (85.35 ± 0.61, IC₅₀ 70) and Al.EaF (83.48 ± 0.67, IC₅₀ 270 μg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC₅₀ 70 μg/mL), Al.SPF, 84.36 ± 0.64 (IC₅₀ 90 μg/mL), Al.MeF, 78.65 ± 0.70 (IC₅₀ 280 μg/mL), Al.EaF, 77.45 ± 0.46 (IC₅₀ 270 μg/mL) and Al.WtF 72.44 ± 0.58 (IC₅₀ 263 μg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC₅₀ 100 μg/mL), Al.CfF 83.49 ± 0.46 (IC₅₀ 160 μg/mL), Al.MeF 82.68 ± 0.60 (IC₅₀ 220 μg/mL) and Al.SPF 80.37 ± 0.54 (IC₅₀ 120 μg/mL).

Conclusions

These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer’s and other neurological disorders.     

A procedure for estimating the relevant forces in the human knee using a four-bar mechanism

Knee injuries, especially those that affect the cruciate and lateral ligaments, are one of the most serious and frequent pathologies that affect the lower human extremity. Hence, the aim of this study is to develop a dynamic model for the lower extremity capable of estimating forces, forces in the cruciate and collateral ligaments and those normal to the articular cartilage, generated in the knee. The proposed model considers a four-bar mechanism in the knee, a spherical joint in the pelvis and a revolute one in the ankle. The four-bar mechanism is obtained by a synthesis process. The dynamic model includes the inertial properties of the femur, tibia, patella and the foot, the ground reaction force and the most important muscles in the knee. Muscle forces are estimated using an optimisation technique. Results from the application of the model on a real human task are presented.     

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.     

Variation in volatile leaf oils of seven eucalyptus species harvested from Zerniza arboreta (Tunisia)

Leaves of seven species of the genus Eucalyptus L'Hér., viz., E. cladocalyx F. Muell., E. citriodora Hook., E. diversicolor F. Muell., E. fasciculosa F. Muell., E. grandis W. Hill, E. ovata Labill., and E. botryoides Sm., were harvested from Zerniza arboreta (region of Sejnene, northwest of Tunisia) in June 2007. Of the latter species, leaves were collected from trees having two origins, Morocco and Italy. Hydrodistillation of the dried leaves provided essential oils in yields varying from 0.4±0.0 to 3.3±0.1%, according to the species. E. citriodora had the highest mean percentage of essential oil amongst the species examined, whereas the lowest one was obtained for E. botryoides originating from Morocco. Analysis by GC (RI) and GC/MS allowed the identification of 140 compounds, representing 92.5 to 99.4% of the total oil composition. The contents of the different samples varied according to the species. The main components were 1,8-cineole (2), followed by α-pinene (1), p-cymene, borneol, α-terpineol, cryptone, spathulenol, trans-pinocarveol (4), bicyclogermacrene (5), caryophyllene oxide, and β-phellandrene. Principal components analysis and hierarchical cluster analysis separated the eight Eucalyptus leaf essential oils into five groups, each constituting a chemotype.     

Biological studies of the predacious mite Amblyseius swirskii,a predator of the broad mite Polyphagotarsonemus latus on pepper plants (Acari: Phytoseiidae: Tarsonemidae)

The predatory phytoseiid mite Amblyseius swirskii (Athias-Henriot) completed its lifespan when fed on females of the broad mite, Polyphagotarsonemus latus (Banks). The development was the quickest and the number of prey consumed was highest when individuals were reared at 28?°C compared with 19?°C. The average number of eggs/female/day was 2.36 and 1.69, respectively. Life table parameters showed that the population of A. swirskii multiplied 16 and 20 times in a generation time of 22 and 18?days at 19 and 28?°C, respectively. Under these conditions, the intrinsic rate of increase (rm) was 0.139 and 0.170 individuals/female/day, respectively.     

Modelling of physical ageing in starch using the TNM equation

Gelatinised wheat starch, freeze dried and equilibrated at different RH, was aged at different temperatures and for different times. The Tool–Narayanaswamy–Moynihan (TNM) model was used to describe the ageing for all samples under all conditions. Three TNM parameters: x, Δh^∗ and A were determined experimentally using, respectively, the peak shift method (x) and the dependency of (the limiting value of T_f) on the cooling rate (Δh^∗ and A). The non-linearity parameter x and the non exponential parameter β were also estimated by optimising a fit of the experimental normalised specific heat at different ageing times and temperatures to curves generated using the TNM model. The TNM model successfully described the normalised experimental data. It was found that the intermolecular forces were strong and the relaxation times depended more strongly on the glass structure than the glass temperature. The hydration level of the starch had a direct impact of the breadth of the relaxation time distribution. A dependency of the non-linearity parameter x on ageing temperature (peak shift method) was observed. This suggests that physical ageing is more complex than is described by TNM formalism.     

Proton NMR-Based Metabolite Analyses of Archived Serial Paired Serum and Urine Samples from Myeloma Patients at Different Stages of Disease Activity Identifies Acetylcarnitine as a Novel Marker of Active Disease

Background

Biomarker identification is becoming increasingly important for the development of personalized or stratified therapies. Metabolomics yields biomarkers indicative of phenotype that can be used to characterize transitions between health and disease, disease progression and therapeutic responses. The desire to reproducibly detect ever greater numbers of metabolites at ever diminishing levels has naturally nurtured advances in best practice for sample procurement, storage and analysis. Reciprocally, since many of the available extensive clinical archives were established prior to the metabolomics era and were not processed in such an ‘ideal’ fashion, considerable scepticism has arisen as to their value for metabolomic analysis. Here we have challenged that paradigm.

Methods

We performed proton nuclear magnetic resonance spectroscopy-based metabolomics on blood serum and urine samples from 32 patients representative of a total cohort of 1970 multiple myeloma patients entered into the United Kingdom Medical Research Council Myeloma IX trial.

Findings

Using serial paired blood and urine samples we detected metabolite profiles that associated with diagnosis, post-treatment remission and disease progression. These studies identified carnitine and acetylcarnitine as novel potential biomarkers of active disease both at diagnosis and relapse and as a mediator of disease associated pathologies.

Conclusions

These findings show that samples conventionally processed and archived can provide useful metabolomic information that has important implications for understanding the biology of myeloma, discovering new therapies and identifying biomarkers potentially useful in deciding the choice and application of therapy.     

Structural modeling studies of aldehyde dehydrogenase X: insights into key interactions in the tetrameric assembly of the isoenzyme

Human mitochondrial aldehyde dehydrogenase is a member of superfamily of multisubunit enzymes, catalyzing the conversion of a broad range of aldehydes to corresponding acids via the NAD (P) (+)-dependent irreversible reaction. They play an important role in the detoxification of acetaldehyde, in the development of alcohol sensitivity and human alcohol-related disorders. The study aimed to understand the role of conserved residues by comparing similarities and differences between the two isoenzymes. A 3D model of the human ALDHX is constructed by molecular modeling based on the crystal structure of human ALDH2 by using MODELLER (8V1) program. Assessment of reliability of the 3D model is carried out by the programs PROCHECK and PROSAII. The ALDHX fold is similar to the previously described ALDH structures. Sequence and structural analyses have highlighted a close structural and functional relationship between the two isoenzymes of human origin. The interfacial residues that are involved in crucial interactions across the interface stabilize the dimer-tetramer interface in the enzyme. Stability factors like salt bonds and hydrogen bonds aid and maintain the tetrameric assembly of the enzyme.