Nuclear Magnetic Resonance Spectral Data Research Articles

Metabolomics Analysis of C. lanceolatum Roots in the Presence of Its Endophytic Fungi

The aim of this work was to identify and quantify the metabolites present in the roots of Combretum lanceolatum inoculated with its endophytic fungi. The metabolomics was accomplished using the 1H nuclear magnetic resonance (NMR) spectral data and evaluated via rNMR software and Madison Metabolomics Consortium Database (MMCD). The principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed that plants inoculated with Trichoderma spirale (Ts) present differentiation and discrimination over the time as compared to control. Seven days after Ts fungal inoculation, 15 metabolites were identified at different concentrations comparing to the control plants. The plants inoculated with Ts fungus present the metabolites spermidine and pantothenate in higher concentrations and 3-hydroxybutyric acid and β-alanine in lower concentrations as compared to control plants, indicating any response to biotic stress. These metabolites are involved in various plant processes, including secondary metabolites biosynthesis, energy metabolism and self-defense. Therefore, this work demonstrates the diversification of primary metabolites composition influenced by endophytes inoculation.

Easy Structural Dereplication of Natural Products by Means of Predicted Carbon‐13 Nuclear Magnetic Resonance Spectroscopy Data**

AbstractThe present article reports the creation and usage of a general natural product database for the structural dereplication of natural products. This database, acd_lotusv7, derives from the LOTUS natural products database as the sole source of chemical structures. Database construction also relies on the commercial “ACD/C+H Predictors and DB” software for the prediction of the carbon‐13 nuclear magnetic resonance (NMR) spectral data associated with structures. The linkage of each natural compound with a Wikidata resource identifier already present in LOTUS accelerates the access to the primary literature data such as biologic origin and bibliographic references. The open source nmrshiftdb2 web interface and search engine provide a simple and free way to retrieve compound structures stored in acd_lotusv7 from carbon‐13 data and to analyze search results. Dereplication is illustrated by the easy and free retrieval of the structure of three natural compounds of low, medium, and high complexity from published lists of carbon‐13 NMR chemical shifts.

ISOLATION, IDENTIFICATION AND BIOASSAY OF FLAVONOIDS FROM Bouea macrophylla GRIFF.

Bouea macrophylla Griff., a species belonging to the Anacardiaceae family is a flowering plant native to Southeast Asia and also known as kundang, kundang daun besar, and setar in Malaysia. The fruit can be eaten raw or as a pickle, while the young leaves can be consumed as salads. It has been claimed to be able to accelerate wound healing, prevent cancer, reduce the risk of stroke, and be good for blood circulation. The previous study on the plant from the same genus, known as B. oppositofolia has shown the presence of various. The present study was designed to isolate and elucidate flavonoids from this plant. The twig extract of kundang was purified by using several chromatographic techniques including Vacuum Liquid Chromatography (VLC), Column Chromatography (CC), and preparative-Thin Layer Chromatography (pTLC). The structures of isolated compounds were characterized by using spectroscopic methods including Nuclear Magnetic Resonance (NMR), infrared (IR), and ultraviolet (UV) spectral data, as well as comparison with the data reported in the literature. Five flavonoids were isolated and purified from the twigs of B. macrophylla which includes one flavanonol known as garbanzol; one flavonol which is resokaempferol; one flavandiol characterized as catechin; and two flavandiol known as mollisacacidin and guibourtacacidin. The results of the glucose uptake experiment indicated that the extract and compounds tested affected the glucose uptake rate of the insulin-resistant C2C12 cell line as compared to the standard. This is the first report describing the elucidation of the stated compounds from B. macrophylla as well as its glucose uptake study.

Curcuminoids from the Vietnamese Curcuma longa: Phytochemical analysis and biological activities

A phytochemical investigation on the ethanolic (EtOH) extract of the Vietnamese Curcuma longa (C. longa) rhizomes has led to the isolation of four curcuminoids including curcumin (1), demethoxycurcumin (2), bisdemethoxycurcumin (3), and cyclocurcumin (4). The chemical structure of compounds 1-4 was elucidated by Nuclear magnetic resonance (NMR) and Mass spectrometry (MS) spectral data. Based on High-performance liquid chromatography (HPLC) quantitative analysis, the amounts of three major compounds 1-3 in the C. longa extract were calculated and reached 7.215±0.101, 3.927±0.031, and 2.255±0.049 mg/g, respectively. Curcuminoids 1-4 have induced IC50 values of 9.23-14.6 μg/ml in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay as compared with that of the positive control resveratrol (IC50 11.5 μg/ml). Compounds 1-4 with IC50 values ranging between 8.7-15.54 μg/ml were better than the positive control acarbose (IC50 169.14 μg/ml) in α-glucosidase inhibitory examination. In addition, the EtOH extract and compounds 1-4 were also responsible for inhibitions against enzyme acetylcholinesterase and four cancer cell lines including including epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), lung cancer (SK-LU-1), and breast cancer (MCF7).

NADES Compounds Identified in Hypoxis hemerocallidea Corms during Dormancy.

Soaking Hypoxis hemerocallidea corms in distilled water improved the propagation and development of cormlets, suggesting the potential leaching-out of inhibitory chemical compounds. To investigate the presence of inhibitory compounds, nuclear magnetic resonance (NMR) spectral data of the leachate from dormant H. hemerocallidea corms were obtained using a 600 MHz 1H-NMR spectrometer. The 1H-NMR analysis led to the identification of choline, succinate, propylene glycol, and lactose, as inhibitory compounds. These four chemical compounds are part of the “Natural Deep Eutectic Solvents” (NADES) that protect plant cells during stress periods, each of which has the potential to inhibit bud growth and development. These compounds are supposedly leached out of the corms during the first rain under natural conditions, possibly accompanied by changes in the ratios of dormancy-breaking phytohormones and inhibitory compounds, to release bud dormancy. The identified chemical compounds heralded a novel frontier in the vegetative propagation of H. hemerocallidea as a medicinal plant, and for its enhanced sustainable uses.

低场核磁共振技术结合机器学习判别水稻种子活力方法研究

Physiological index data and low-field nuclear magnetic resonance (LF-NMR) spectral data of rice seed samples from three varieties harvested in different years were collected through a combination of the standard germination test and an LF-NMR test. Three parameters of seed vigor: germination energy, germination percentage, and germination index, were calculated based on the physiological index data of the rice seed samples to determine their vigor over the years after harvest. LF-NMR Carr-Purcell-Meiboom-Gill (CPMG) sequence echo-peak data were used as the input, and rice seed vigor was used as the output to establish discriminative models using principal component analysis, support vector machine, logistic regression, K-nearest neighbor, artificial neural network, and Fisher’s linear discriminant. The results showed that models constructed using any algorithm, except for principal components analysis-algorithm distinguished between seeds with high and low vigor, while models constructed using Fisher’s linear discriminant algorithm gave the best results. This study provided a rapid, accurate, and non-destructive method to test rice seed vigor, offering theoretical support and a reference for rice seed-sorting and storage research.

One step protocol and green synthesis of 2-N,N-dimethylamino-3-alkyl(aryl)-2-oxido-1- hydro-2-benzo[1,3,2]diazaphosphinine-4-one derivatives

ABSTRACT. 2-N,N-dimethylamino-2-oxido-3-alkyl(aryl)-1-hydro-2-benzo[1,3,2]diazaphosphinin-4-one (2) derivatives are synthesized by one pot reaction by reacting equimolar quantities of anthranilic acid, primary amine, and N,N-dimethylphosphoramic dichloride under reflux of ethanol with good yields. The structure of the compounds were established on the basis of their infrared, nuclear magnetic resonance spectral data (1H NMR, 13C NMR and 31P NMR), mass spectrometry, and elemental analysis.
 
 KEY WORDS: Anthranilic acid, N,N-Dimethylphosphoramic dichloride, Diazaphosphinine
 Bull. Chem. Soc. Ethiop. 2022, 36(4), 859-864. 
 
 DOI: https://dx.doi.org/10.4314/bcse.v36i4.11

Green Synthesis, Biological Evaluation, and Molecular Docking of 4'-(Substituted Phenyl)Spiro[Indoline-3,3'-[1,2,4]Triazolidine]-2,5'-Diones

We reported herein a green and efficient catalyst-free synthesis of 4'-(substituted phenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-diones (3a–g) in excellent yields. A one-pot multi-component synthesis was achieved using a glycerol-water (4:1) green solvent system. The current synthetic procedure has the advantage of being environmentally friendly, catalyst free, and having a simple workup with high yields. The structure of the title compounds (3a–g) was confirmed by infrared (IR), nuclear magnetic resonance (NMR) and mass spectral data, followed by their biological evaluation. Using the standard protocol, all of the compounds were tested for antibacterial, antifungal, and antitubercular activities. 4'-(4-Chlorophenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-dione (3b) was found to be the most potent compound in the series, with MIC values ranging from 12.71 to 50.84 M, but it was found to be inactive against Mycobacterium tuberculosis H37Ra and M. bovis. 4'-(4-Methoxyphenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-dione (3e) displayed significant antifungal activity with MIC values of 12.89 and 25.78 µM. The SwissADME prediction studies of revealed that the compounds (3a–g) followed the Lipinski rule of 5 and have good absorption from gastrointestinal tract. The title compounds were also investigated using molecular docking against bacterial DNA gyrase (PDB ID: 1KZN).

Antinociceptive activity of the Caesalpinia eriostachys Benth. ethanolic extract, fractions, and isolated compounds in mice.

Caesalpinia eriostachys Benth. (CE) is native to the Mexico and multiple effects have been observed from several plants belonging to the same family. CE was subjected to extraction with 95% ethanol, and the components were isolated through column chromatography. The structure of the compound was elucidated based on nuclear magnetic resonance (NMR) spectral data, electron ionization–mass (EI‐MS) spectroscopy, and liquid chromatography–mass (LC‐MS) spectroscopy. In vivo antinociceptive studies were conducted using writhing, 5% formalin, tail‐flick, hot‐plate, and von Frey filament tests. The ethanolic extract showed a significant effect in the acetic acid‐induced pain model and nociceptive behavior in the formalin model (second phase). In hot‐plate test and tail‐flick test, the results showed no difference compared to the control group. The results suggest that the ethanolic extract may act peripherally to reduce pain. In the streptozotocin (STZ)‐induced pain model, the ethanolic extract showed significant effect in the von Frey test model. The n‐Hex (Hexane) and MC (Methylene chloride) fractions and isolated compounds, ellagic acid and agathisflavone, showed increased effect. Based on these results, we confirmed that the CE ethanolic extract and their compounds, ellagic acid and agathisflavone, have antinociceptive effect on diabetes mellitus‐induced pain. Furthermore, the results of this study might be valuable for identifying compounds with antinociceptive activity from natural products.

Lignans and Other Compounds From the Roots of Pandanus tonkinensis and Their Lipid Peroxidation Inhibitory Activity

A new phenylpropane (1) and 9 known (2-10) compounds were isolated from the methanol extract of Pandanus tonkinensis roots. Their chemical structures were determined as (7 S)-2,6-dimethoxyphenyl-7,9-propanediol-1 -O-β-D-glucopyranoside (1), isorhapontigenin (2), pinoresinol-4,4′-di -O-β-D-glucoside (3), isoeucommin A (4), pinoresinol-4′ -O-β-D-glucoside (5), acanthoside B (6), eucommin A (7), urolignoside (8), benzyl O-α-L-arabinopyranosyl-(1→6) -β-D-glucopyranoside (9), and (6 S,9 S)-roseoside (10) by comprehensive analysis of high-resolution electron spray ionization mass spectrum and nuclear magnetic resonance spectral data, as well as by comparison of their spectral data with those reported in the literature. In addition, the stereochemistry of 1 was successfully determined by both theoretical and calculated CD spectra. All the isolates were tested for their lipid peroxidation inhibitory effects by in vitro assay. Compounds 2-7 exhibited significantly lipid peroxidation inhibitory effects with IC50 values of 21.3 ± 1.7, 61.9 ± 3.9, 57.5 ± 5.5, 10.4 ± 0.7, 28.9 ± 0.3, 54.2 ± 3.5 µM, respectively, compared to that of the positive control, trolox (31.4 ± 2.2 µM).

Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2'-(2-Oxo-1H-benzo[d]imidazole-1,3(2H)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives.

To identify new candidate anticancer compounds, we here report the synthesis of benzimidazole derivatives: diethyl 2,2′-(2-oxo-1H-benzo[d]imidazole-1,3(2H)-diyl) diacetate and its arylideneacetohydrazide derivatives, using ultrasonic irradiation and conventional heating. The compounds were confirmed by Nuclear magnetic resonance (NMR) (JEOL, Tokyo, Japan) and Fourier transform infrared spectroscopy (FTIR) spectroscopy (Thermoscientific, Waltham, MA, USA). The molecular structure and electronic properties of the studied compounds were predicted for the acetohydrazide hydrazones. These compounds exist as a mixture of configurational and conformational isomerism as well as amido-amidic acid tautomerism. The NMR spectral data proved the predominance of syn-E amido isomers. In addition, density functional theory (DFT) predicted stability in the gas phase and showed that syn-E amido isomers are the most stable in the presence of an electron donating group, while the anti-isomer is the most stable in the presence of electron-attracting substituents. The anticancer activity of these synthetic compounds 6a, 6b and 6c towards both colon cancer (HCT-116) and cervical cancer (HeLa) cells was examined by MTT assay and DAPI staining. The MTT assay revealed a strong antiproliferative effect against the cancer cells at low concentrations, and interestingly, no significant inhibitory action against the non-cancerous cell line, HEK-293. The IC50 values for HCT-116 were 29.5 + 4.53 µM, 57.9 + 7.01 µM and 40.6 + 5.42 µM for 6a, 6b, and 6c, respectively. The IC50 values for HeLa cells were 57.1 + 6.7 µM, 65.6 + 6.63 µM and 33.8 + 3.54 µM for 6a, 6b, and 6c, respectively. DAPI staining revealed that these synthesized benzimidazole derivatives caused apoptotic cell death in both the colon and cervical cancer cells. Thus, these synthetic compounds demonstrate encouraging anticancer activity as well as being safe for normal human cells, making them attractive candidates as anticancer agents.

NMR as Used in the Russian and Foreign Pharmacopoeias for Quality Control of Medicinal Products

The ongoing development of the Pharmacopoeia of the Eurasian Economic Union and the current trend for harmonisation of the Russian Pharmacopoeia with the world leading pharmacopoeias suggest the necessity of studying how different pharmacopoeias use nuclear magnetic resonance (NMR) for quality control of medicinal products. The aim of the study was to compare the extent of medicine quality characteristics assessed by NMR in the Russian and foreign pharmacopoeias. The review summarises the experience of various national and world pharmacopoeias in using the NMR method for quality control of medicines and certification of pharmacopoeial reference materials. The comparative analysis covered the following quality parameters: active ingredient identification, determination of the composition of non-stoichiometric compounds, determination of the average polymer chain length in polymers and block copolymers, determination of the absolute content of the active ingredient, identification and quantification of impurities, polymorphism, and crystallinity. It was shown that the United States and Japanese Pharmacopoeias are leading the way in introducing the NMR method into pharmacopoeial analysis. There have been some positive trends in the introduction of the NMR method in the State Pharmacopoeia of the Russian Federation as well. It was concluded that changes are needed in the general chapters “Nuclear Magnetic Resonance Spectroscopy” and “Reference Standards” of the State Pharmacopoeia of the Russian Federation, 14th ed. in order to harmonise the texts with those of the Eurasian Pharmacopoeia and the European Pharmacopoeia and to allow for the possibility of direct identification of a substance by complex analysis of NMR spectral data, without comparing the test sample and the reference standard spectra. The NMR method should be included in the list of absolute methods used for determination of purity of primary chemical reference substances during certification.

Phytochemical Analysis, Tuberculosis Effect, Purification and Characterization of Aerial Parts of Avicennia alba

The present study deals with phytochemical, pharmacological (In vitro antioxidant), purification and characterization studies of aerial parts of Avicennia alba. The phytochemical analysis for qualitative and quantitative investigation revealed the presence of more bioactive compounds in methanolic extract than hexane and chloroform extracts of Avicennia alba. The methanolic extract showed better activity on 2,2-diphenyl-1-picrylhydrazyl free radical than remaining free radical tests i.e hydrogen peroxide and hydroxyl radical. The methanolic extract was potent in inhibiting the free radicals upon comparison with standard ascorbic acid. The tuberculosis effect of the plant was not up to the mark when compared with standard control. The methanolic plant extract was subjected to column chromatography and three compounds were isolated. The isolated compounds were characterized by ultraviolet, fourier transform infrared spectroscopy, proton nuclear magnetic resonance, carbon nuclear magnetic resonance and mass spectral data studies and were identified as stigmasterol, beta-sitosterol and lupeol. The work carried out was distinctive as the source of plant was taken from coringa mangrove, Kakinada, first of its kind and the tuberculosis effect was also reported for the first time, though it was not up to the mark the work reported inspires the researcher to enlighten and save their time. The natural compounds selected were reported previously but an in depth characterization was reported for a thorough look.

Isolation and characterization of anti-tumor compounds from ethyl acetate extract of Rumex japonicus houtt roots and their cytotoxic effects

To isolate and characterize anti-tumor compounds through nuclear magnetic resonance (NMR) spectroscopy of ethyl acetate extract of R. japonicus Houtt root and their cytotoxic effects were evaluated in terms of measuring inhibition of growth of three cancer cell lines: human hepatoma cells (HepG2), cerebral glioma cells (U251) and ovarian carcinoma cells (SK-OV-3/DDP). The roots of R. japonicus Houtt were extracted with ethanol, and partitioned with petroleum ether, dichloromethane and ethyl acetate, respectively. The ethyl acetate extract was separated chromatographically using macroporous resin, positive and negative phase silica gel and high performance liquid chromatography. The structures of isolated compounds were elucidated by nuclear magnetic resonance (NMR) spectral data. Ten compounds were isolated form the ethyl acetate extract of R. japonicus roots. Their structures were determined as emodin (1), chrysophanol (2), aloe emodin (3), physcion (4), quercetin (5), resveratrol (6), β-sitosterol (7), 3β-acetoxy-28-hydroxyurs-12-ene (8), sucrose (9) and dibutyl phthalate (10). Among of them, compounds 1, 3, 4, 6 and 8 exhibited highly significant (p<0.05) cytotoxicities against HepG2 to a certain extent. Compounds 3-6 exhibited moderate cytotoxicities against U251 with IC50 values of 19.8, 23.5, 23.8 and 17.8 µM, respectively. Compounds 1, 2 and 7 also exhibited cytotoxicities against U251 to a certain extent with IC50 values of 48.3, 50.1 and 85.3 µM, respectively. Compounds 1-6 exhibited moderate cytotoxicities against (SK-OV-3/DDP) with IC50 values of 62.8, 64.2, 31.3, 61.0, 47.4 and 42.0 µM, respectively.

Four New Acyclic Diterpenes From Siegesbeckia orientalis

Four new acyclic diterpenes, siegetalises A-D (1-4), were isolated from the aerial parts of Siegesbeckia orientalis. Their chemical structures were elucidated by extensive analysis of high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectral data. The effects of the isolated compounds on the activity of xanthine oxidase were evaluated by the oxidative reaction with xanthine as a substrate. At a concentration of 50 µM, compounds 1-4 exhibited xanthine oxidase inhibitory activity at levels of 13.59% ± 0.51%, 19.64% ± 1.54%, 17.45% ± 1.26%, and 21.36% ± 1.40%, respectively.

SYNTHESIS OF 1-BENZOYL-3-PHENYL-1H-PYRAZOLE-4-CARBALDEHYDE AND EVALUATION OF THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITY

Objective: The main objective of this study is to synthesize a series of 1-Benzoyl-3-phenyl-1H-pyrazole-4-carbaldehyde (4a-e) derivatives and evaluation of the synthesized compounds for their antioxidant and anti-inflammatory activity. Methods: A series of substituted acetophenones are condensed with hydrazides to the corresponding hydrazones which are subsequently cyclized by using vilsmier-Haack reaction to give final series of 1-Benzoyl-3-phenyl-1H-pyrazole-4-carbaldehyde (4a-e) derivatives respectively. All newly synthesized compounds were characterized on the basis of infrared, proton nuclear magnetic resonance and mass spectral data and screened for their antioxidant and anti-inflammatory activities. Results: In view of the significant biological activity profile of Pyrazole, the synthesized compounds (4a-e) were evaluated for their antioxidant potency by DPPH, Nitric oxide, Hydroxyl radical scavenging, and Hydrogen Peroxide method. Compounds 4c and 4e showed potent antioxidant activity then standard. Synthesized compounds were also screened for anti-inflammatory activity. Among all the molecules 4c, 4e, and 4d showed significant activity as compared to standard drug diclofenac sodium. Conclusion: in this study, we synthesized 1-Benzoyl-3-phenyl-1H-pyrazole-4-carbaldehyde (4a-e) derivatives. Further, these derivatives showed significant antioxidant and anti-inflammatory activity. Among them, two molecules 4c and 4e have shown near action to the standard.

Separation and Characterization of Novel Degradation and Process Related Impurities of Bedaquiline Bulk Drug

Bedaquiline (BDQ) is a new drug approved by United States Food and Drug Administration (USFDA) in 2012 for the treatment of drug-resistant tuberculosis, which has become a major threat globally. The manuscript presents the development of three liquid chromatography (LC) based analytical methods. The first is a stability indicating RP-HPLC (reverse phase-high performance liquid chromatography) method to analyze the BDQ in presence of its degradation products. Another UPLC/ESI–MS (ultra-performance liquid chromatography/electron spray ionization–mass spectrometry) method was developed for the identification of different degradation based and process related impurities and the third, preparative HPLC method was developed for the isolation of major degradation products. Eleven degradation products and one process related impurity were identified using UPLC/ESI–MS whereas preparative HPLC was used to isolate two degradation products and their chemical structure was elucidated using nuclear magnetic resonance, mass and infra-red spectral data.

New Nitric Oxide Inhibitory Spirostane Glycosides from Polygonatum kingianum Collett &amp; Hemsl

Two new spirostane glycosides, (25 R)-12 β-hydroxyspirost-5-en-3 β-yl O- β-D-glucopyranosyl-(1→4)- β-D-galactopyranoside (1) and (25 S)-spirost-5-en-7-one-3 β-yl O- β-D-glucopyranosyl-(1→2)- β-D-glucopyranosyl-(1→4)- β-D-galactopyranoside (2), and a known spirostane glycoside, funkioside C (3), were isolated from the roots of Polygonatum kingianum Collett &amp; Hemsl. (Asparagaceae). Their structures were determined by extensive analysis of mass spectrometry high resolution electron spray ionization mass spectrum and nuclear magnetic resonance spectral data, as well as by comparison of the spectral data with those reported in the literature. Compound 2 showed inhibitory effects on nitric oxide production in the lipopolysaccharide stimulated RAW 264.7 cells with an IC50 value of 8.78 ± 0.05 µM compared to a value of 7.12 ± 0.08 µM for the positive control compound, NG-monomethyl-L-arginine.

Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model

ABSTRACT Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.

Aramatosides C and D, 2 Previously Undescribed Triterpene Glycosides Isolated From the Roots of Aralia armata

The 2 new oleanane-type triterpene glycosides, 23-hydroxyoleanolic acid-[28- O- β-D-glucopyranosyl]-3- O-{ β-D-glucopyranosyl-(1→2)-[ β-D-glucopyranosyl-(1→3)]- β-D-galactopyranoside}, (1) and oleanolic acid-[28- O- β-D-glucopyranosyl]-3- O-{ β-D-glucopyranosyl-(1→2)-[ β-D-glucopyranosyl-(1→3)]- β-D-galactopyranoside} (2) were isolated from the roots of Aralia armata. Their chemical structures were elucidated by using a combination of high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1 dimensional (1D), and 2 dimensional (2D) nuclear magnetic resonance spectral data, as well as by comparison with the previous literature. Compounds 1 and 2 displayed weak cytotoxic activity toward KB and HepG2 cell lines with IC50 values of 25.1 ± 1.2 and 23.7 ± 0.9 µM (for 1) and 29.5 ± 1.3 and 23.9 ± 0.7 µM (for 2), respectively, compared to that of the positive control compound, ellipticine (IC50: 1.3 ± 0.1 and 1.6 ± 0.1 µM, respectively) in in vitro assay.