Ahmed Mediani

Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract.

Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.

Cosmos Caudatus as a Potential Source of Polyphenolic Compounds: Optimisation of Oven Drying Conditions and Characterisation of Its Functional Properties

The aim of the study was to analyze the influence of oven thermal processing of Cosmos caudatus on the total polyphenolic content (TPC) and antioxidant capacity (DPPH) of two different solvent extracts (80% methanol, and 80% ethanol). Sonication was used to extract bioactive compounds from this herb. The results showed that the optimised conditions for the oven drying method for 80% methanol and 80% ethanol were 44.5 °C for 4 h with an IC50 of 0.045 mg/mL and 43.12 °C for 4.05 h with an IC50 of 0.055 mg/mL, respectively. The predicted values for TPC under the optimised conditions for 80% methanol and 80% ethanol were 16.5 and15.8 mg GAE/100 g DW, respectively. The results obtained from this study demonstrate that Cosmos caudatus can be used as a potential source of antioxidants for food and medicinal applications.

Antioxidant, Antityrosinase, Anticholinesterase, and Nitric Oxide Inhibition Activities of Three Malaysian Macaranga Species

The methanol extracts of three Macaranga species (M. denticulata, M. pruinosa, and M. gigantea) were screened to evaluate their total phenolic contents and activities as cholinesterase inhibitors, nitric oxide (NO) production inhibitors, tyrosinase inhibitors, and antioxidants. The bark of M. denticulata showed the highest total phenolic content (2682 mg gallic acid equivalent (GAE)/100 g) and free radical scavenging activity (IC50 = 0.063 mg/mL). All of the samples inhibited linoleic acid peroxidation by greater than 80%, with the leaves of M. gigantea exhibiting the highest inhibition of 92.21%. Most of the samples exhibited significant antioxidant potential. The bark of M. denticulata and the leaves of both M. pruinosa and M. gigantea exhibited greater than 50% tyrosinase inhibition, with the bark of M. denticulata having the highest percentage of inhibition (68.7%). The bark and leaves of M. denticulata exhibited greater than 50% inhibition (73.82% and 54.50%, resp.) of the acetylcholinesterase enzyme (AChE), while none of the samples showed any significant inhibition of butyrylcholinesterase (BChE). Only the bark of M. denticulata and M. gigantea displayed greater than 50% inhibition of nitric oxide production in cells (81.79% and 56.51%, resp.). These bioactivities indicate that some Macaranga spp. have therapeutic potential in medicinal research.

Effects of Different Drying Methods and Storage Time on Free Radical Scavenging Activity and Total Phenolic Content of Cosmos Caudatus.

The present study was conducted to determine the effect of air (AD), oven (OD) and freeze drying (FD) on the free radical scavenging activity and total phenolic content (TPC) of Cosmos caudatus and the effect of storage time by the comparison with a fresh sample (FS). Among the three drying methods that were used, AD resulted in the highest free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50 = 0.0223 mg/mL) and total phenolic content (27.4 g GAE/100 g), whereas OD produced the lowest scavenging activity and TPC value. After three months of storage, the dried samples showed a high and consistent free radical scavenging activity when compared to stored fresh material. The drying methods could preserve the quality of C. caudatus during storage and the stability of its bioactive components can be maintained.

Metabolite profiling, antioxidant, and α-glucosidase inhibitory activities of germinated rice: nuclear-magnetic-resonance-based metabolomics study

In an attempt to profile the metabolites of three different varieties of germinated rice, specifically black (GBR), red, and white rice, a 1H-nuclear-magnetic-resonance-based metabolomics approach was conducted. Multivariate data analysis was applied to discriminate between the three different varieties using a partial least squares discriminant analysis (PLS-DA) model. The PLS model was used to evaluate the relationship between chemicals and biological activities of germinated rice. The PLS-DA score plot exhibited a noticeable separation between the three rice varieties into three clusters by PC1 and PC2. The PLS model indicated that α-linolenic acid, γ-oryzanol, α-tocopherol, γ-aminobutyric acid, 3-hydroxybutyric acid, fumaric acid, fatty acids, threonine, tryptophan, and vanillic acid were significantly correlated with the higher bioactivities demonstrated by GBR that was extracted in 100% ethanol. Subsequently, the proposed biosynthetic pathway analysis revealed that the increased quantities of secondary metabolites found in GBR may contribute to its nutritional value and health benefits.

Characterization of metabolites in different kiwifruit varieties by NMR and fluorescence spectroscopy

&NA; It is known from our previous studies that kiwifruits, which are used in common human diet, have preventive properties of coronary artery disease. This study describes a combination of 1H NMR spectroscopy, multivariate data analyses and fluorescence measurements in differentiating of some kiwifruit varieties, their quenching and antioxidant properties. A total of 41 metabolites were identified by comparing with literature data Chenomx database and 2D NMR. The binding properties of the extracted polyphenols against HSA showed higher reactivity of studied two cultivars in comparison with the common Hayward. The results showed that the fluorescence of HSA was quenched by Bidan as much as twice than by other fruits. The correlation between the binding properties of polyphenols in the investigated fruits, their relative quantification and suggested metabolic pathway was established. These results can provide possible application of fruit extracts in pharmaceutical industry. Graphical abstract Figure. No caption available. HighlightsNMR‐based metabolomic analysis of different kiwifruit varieties is reported.Total phenolics, flavonoids, antioxidant and binding activities of kiwifruit extracts in vitro assays were done.The presence of the metabolites suggested by the NMR analysis was verified.The interaction between HSA and phenolic extracts was investigated in vitro.Phenolics bind to HSA with moderately strong binding affinity.

Metabolite Variation in Lean and Obese Streptozotocin (STZ)-Induced Diabetic Rats via 1H NMR-Based Metabolomics Approach

Diabetes mellitus (DM) is considered as a complex metabolic disease because it affects the metabolism of glucose and other metabolites. Although many diabetes studies have been conducted in animal models throughout the years, the pathogenesis of this disease, especially between lean diabetes (ND + STZ) and obese diabetes (OB + STZ), is still not fully understood. In this study, the urine from ND + STZ, OB + STZ, lean/control (ND), and OB + STZ rats were collected and compared by using 1H NMR metabolomics. The results from multivariate data analysis (MVDA) showed that the diabetic groups (ND + STZ and OB + STZ) have similarities and dissimilarities for a certain level of metabolites. Differences between ND + STZ and OB + STZ were particularly noticeable in the synthesis of ketone bodies, branched-chain amino acid (BCAA), and sensitivity towards the oral T2DM diabetes drug metformin. This finding suggests that the ND + STZ group was more similar to the T1DM model and OB + STZ to the T2DM model. In addition, we also managed to identify several pathways and metabolism aspects shared by obese (OB) and OB + STZ. The results from this study are useful in developing drug target-based research as they can increase understanding regarding the cause and effect of DM.

1 H NMR and antioxidant profiles of polar and non-polar extracts of persimmon ( Diospyros kaki L.) – Metabolomics study based on cultivars and origins

Persimmon (Diospyros kaki L.) is one of the most important fruits that has been consumed for its medicinal properties due to the presence of some active metabolites, particularly polyphenols and carotenoids. Previously described methods, including HPLC, were limited in the determination of metabolites in different persimmon varieties. The present study shows the evaluation and the differences among persimmon polar and non-polar extracts by 1H NMR-based metabolomics approach. The hierarchical clustering analysis (HCA) based on score values of principal component analysis (PCA) model was used to analyze the important compounds in investigated fruits. The 1H NMR spectrum of persimmon chloroform (CDCl3) extracts showed different types of compounds as compared to polar methanol-water (CD3OD-D2O) ones. Persimmons growing in Israel were clustered different from those growing in Korea with the abundance of phenolic compounds (gallic, caffeic and protocathecuic acids), carotenoids (β-cryptoxanthin, lutein, and zeaxanthin), amino acids (alanine), maltose, uridine, and fatty acids (myristic and palmitoleic acids). Glucose, choline and formic acid were more prominent in persimmon growing in Korea. In CD3OD-D2O and CDCl3 persimmon extracts, 43 metabolites were identified. The metabolic differences were shown as well on the results of bioactivities and antioxidant capacities determined by ABTS, FRAP, CUPRAC and DPPH assays. The presented methods can be widely used for quantitation of multiple compounds in many plant and biological samples especially in vegetables and fruits.

Characterization of Metabolite Profile in Phyllanthus niruri and Correlation with Bioactivity Elucidated by Nuclear Magnetic Resonance Based Metabolomics

Phyllanthus niruri is an important medicinal plant. To standardize the extract and guarantee its maximum benefit, processing methods optimization ought to be amenable and beneficial. Herein, three dried P. niruri samples, air (AD), freeze (FD) and oven (OD), extracted with various ethanol to water ratios (0%, 50%, 70%, 80% and 100%) were evaluated for their metabolite changes using proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach. The amino acids analysis showed that FD P. niruri exhibited higher content of most amino acids compared to the other dried samples. Based on principal component analysis (PCA), the FD P. niruri extracted with 80% ethanol contained higher amounts of hypophyllanthin and phenolic compounds based on the loading plot. The partial least-square (PLS) results showed that the phytochemicals, including hypophyllanthin, catechin, epicatechin, rutin, quercetin and chlorogenic, caffeic, malic and gallic acids were correlated with antioxidant and α-glucosidase inhibitory activities, which were higher in the FD material extracted with 80% ethanol. This report optimized the effect of drying and ethanol ratios and these findings demonstrate that NMR-based metabolomics was an applicable approach. The FD P. niruri extracted with 80% ethanol can be used as afunctional food ingredient for nutraceutical or in medicinal preparation.

Application of BATMAN and BAYESIL for quantitative 1 H-NMR based metabolomics of urine: discriminant analysis of lean, obese, and obese-diabetic rats

IntroductionBATMAN and BAYESIL are software tools, which can provide a solution for automated metabolite quantifications based on the proton nuclear magnetic resonance (1H-NMR) spectral data of bio-fluids. However, their specific application for the quantitative 1H-NMR based metabolomics of urine has not been investigated.ObjectivesThe aim of this study is to evaluate the performance of BATMAN and BAYESIL in the quantitative metabolite analysis of urine based on its 1H-NMR spectra.MethodsBATMAN and BAYESIL were used for automated metabolite quantification based on the 1H-NMR spectra of the urine from the lean, obese and obese-diabetic rat groups. PLS-DA model was used to discriminate the three different groups based on the results from the quantifications.ResultsBATMAN was found to be superior to BAYESIL in identifying and quantifying the metabolites in the urine samples, owing to its flexibility that allows users to define and adjust the relevant signals of the pure standard metabolites in the database in order to fit the signals in the samples, a necessary step since variations and peak shift are natural in most 1H-NMR spectra. The results of BATMAN also agreed well with that of the manual deconvolution method, which indicated the higher accuracy in metabolite quantification, despite the need of pre-processing and longer processing time than BAYESIL. However, in the case where the problems in baseline correction and peak shift of 1H-NMR spectra are absent, the use of BAYESIL is more advantageous. Application of quantitative 1H-NMR based metabolomics of the urine showed that PLS-DA model derived from BATMAN could satisfactorily discriminate the lean, obese, and obese-diabetic rat groups.ConclusionBoth BATMAN and BAYESIL are useful for the quantitative automation of urine metabolites based on its 1H-NMR spectra. The results from BATMAN method is superior to BAYESIL but require expertise in spectroscopy and longer computer time. Both methods help in simplifying the interpretation of metabolite status in the VIP analysis.