The cortical representation of language timescales is shared between reading and listening.

Language comprehension involves integrating low-level sensory inputs into a hierarchy of increasingly high-level features. Prior work studied brain representations of different levels of the language hierarchy, but has not determined whether these brain representations are shared between written and spoken language. To address this issue, we analyze fMRI BOLD data that were recorded while participants read and listened to the same narratives in each modality. Levels of the language hierarchy are operationalized as timescales, where each timescale refers to a set of spectral components of a language stimulus. Voxelwise encoding models are used to determine where different timescales are represented across the cerebral cortex, for each modality separately. These models reveal that between the two modalities timescale representations are organized similarly across the cortical surface. Our results suggest that, after low-level sensory processing, language integration proceeds similarly regardless of stimulus modality.

The Cortical Representation of Language Timescales is Shared between Reading and Listening.

Language comprehension involves integrating low-level sensory inputs into a hierarchy of increasingly high-level features. Prior work studied brain representations of different levels of the language hierarchy, but has not determined whether these brain representations are shared between written and spoken language. To address this issue, we analyzed fMRI BOLD data recorded while participants read and listened to the same narratives in each modality. Levels of the language hierarchy were operationalized as timescales, where each timescale refers to a set of spectral components of a language stimulus. Voxelwise encoding models were used to determine where different timescales are represented across the cerebral cortex, for each modality separately. These models reveal that between the two modalities timescale representations are organized similarly across the cortical surface. Our results suggest that, after low-level sensory processing, language integration proceeds similarly regardless of stimulus modality.

Phonemic segmentation of narrative speech in human cerebral cortex.

Speech processing requires extracting meaning from acoustic patterns using a set of intermediate representations based on a dynamic segmentation of the speech stream. Using whole brain mapping obtained in fMRI, we investigate the locus of cortical phonemic processing not only for single phonemes but also for short combinations made of diphones and triphones. We find that phonemic processing areas are much larger than previously described: they include not only the classical areas in the dorsal superior temporal gyrus but also a larger region in the lateral temporal cortex where diphone features are best represented. These identified phonemic regions overlap with the lexical retrieval region, but we show that short word retrieval is not sufficient to explain the observed responses to diphones. Behavioral studies have shown that phonemic processing and lexical retrieval are intertwined. Here, we also have identified candidate regions within the speech cortical network where this joint processing occurs.

Semantic Representations during Language Comprehension Are Affected by Context.

The meaning of words in natural language depends crucially on context. However, most neuroimaging studies of word meaning use isolated words and isolated sentences with little context. Because the brain may process natural language differently from how it processes simplified stimuli, there is a pressing need to determine whether prior results on word meaning generalize to natural language. fMRI was used to record human brain activity while four subjects (two female) read words in four conditions that vary in context: narratives, isolated sentences, blocks of semantically similar words, and isolated words. We then compared the signal-to-noise ratio (SNR) of evoked brain responses, and we used a voxelwise encoding modeling approach to compare the representation of semantic information across the four conditions. We find four consistent effects of varying context. First, stimuli with more context evoke brain responses with higher SNR across bilateral visual, temporal, parietal, and prefrontal cortices compared with stimuli with little context. Second, increasing context increases the representation of semantic information across bilateral temporal, parietal, and prefrontal cortices at the group level. In individual subjects, only natural language stimuli consistently evoke widespread representation of semantic information. Third, context affects voxel semantic tuning. Finally, models estimated using stimuli with little context do not generalize well to natural language. These results show that context has large effects on the quality of neuroimaging data and on the representation of meaning in the brain. Thus, neuroimaging studies that use stimuli with little context may not generalize well to the natural regime.SIGNIFICANCE STATEMENT Context is an important part of understanding the meaning of natural language, but most neuroimaging studies of meaning use isolated words and isolated sentences with little context. Here, we examined whether the results of neuroimaging studies that use out-of-context stimuli generalize to natural language. We find that increasing context improves the quality of neuro-imaging data and changes where and how semantic information is represented in the brain. These results suggest that findings from studies using out-of-context stimuli may not generalize to natural language used in daily life.

Massachusetts General Hospital Hairpulling Scale: Validity and Reliability Study of the Turkish Form. / Massachusetts Genel Hastane Saç/Kil Yolma Ölçegi: Türkçe Formunun Geçerlik ve Güvenirlik Çalismasi.

OBJECTIVE: The aim of this study is to analyze the validity and reliability of the Turkish form of Massachusetts General Hospital Hairpulling Scale (MGH-HPS), which is used to measure the severity of Trichotillomania (TTM). METHODS: Fifty patients diagnosed with TTM according to the DSM-5 diagnostic criteria and fifty healthy controls participated in the study. The participants were asked to complete a sociodemographic questionnaire, the MGH-HPS-TR, the Clinical Global Impression (CGI), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the Barratt Impulsiveness Scale (BIS-11). The construct validity and the criterion validity of the MGH-HPS-TR were determined by means of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), respectively. The reliability analysis of the MGH-HPS-TR was assessed by calculating the Cronbach's α coefficient and the item total correlation coefficient. The values for the area under the curve (AUC), sensitivity and specificity were based on the ROC analysis. RESULTS: AFA and CFA results indicated a single factor structure with 7 items explaining 82.5% of the variance. The item/factor loadings were satisfactory with the best fit indeces. Correlations were found between the scores on the MGH-HPS-TR and the other scales used for criterion validity analyses. The internal consistency and the item-total correlation coefficients of the scale were found to be satisfactory. Based on a cut of point of ≥ 9, the scale had high power for discriminating between the patient and the control groups and high sensitivity and specificity. CONCLUSION: This study showed that the MGH-HPS-TR can be used as a valid and reliable psychometric tool in Turkey.

Absolute configuration of spiro-flavostilbenoids from Yucca schidigera Roezl ex Ortgies: First indication of (2R)-naringenin as the key building block.

The absolute configurations of the known but unusual spiro-flavostilbenoids found in the bark of Yucca schidigera Roezl ex Ortgies, were determined by applying time-dependent density functional theory simulation of electronic circular dichroism spectra. The absolute configurations obtained were as follows: (2S,3R) for yuccaol A, yuccaol D and yuccalide A; (2S,3S) for yuccaol B, yuccaol C and yuccaol E; (2S,3S,2'S,3'S) for gloriosaol A; (2S,3R,2'S,3'R) for gloriosaol C; (2S,3S,2'S,3'R) for gloriosaol D; (2S,3R,2'S,3'S) for gloriosaol E. These findings indicate that the compounds are all biosynthetic derivatives either of (2R)-naringenin and trans-resveratrol or of trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene. In contrast, gloriosaols are direct derivatives of yuccaols (note that substituting by stilbenoid changes the absolute configuration of C-2 naringenin carbon to 2S). A putative mechanism for their biosynthesis is proposed taking into account key aspects of regio- and stereoselectivity. Yuccaol B and gloriosaol A showed in vitro moderate inhibitory effects against acetyl-/butyrylcholinesterases (AChE/BChE) with IC50 values of 43/81 and 45/65 µM respectively. The selectivity index values calculated from the IC50 values of BChE and AChE were 1.9 and 1.4. Molecular docking simulations showed their interaction with the peripheral anionic site of human AChE and the catalytic site of the human BChE.

X-ray crystalographic data, absolute configuration, and anticholinesterase effect of dihydromyricitrin 3-O-rhamnoside.

Based on our continuous effort to investigate chemistry and biology of the plant secondary metabolites, we were able to isolate a glycosidal flavonoid 1 from the Wild Egyptian Artichoke. The activity of dihydromyricetin 3-O-rhamnoside (sin. dihydromyricitrin, ampelopsin 3-O-rhamnoside) (1) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE); its absolute configuration using X-ray crystallography were determined for the first time. Inhibitory activity of 1 against AChE and BChE enzymes were determined using a slightly modified version of Ellman's method. Compound 1 was revealed to have a potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 0.070 ± 0.008 and 0.071 ± 0.004 mM, respectively, where IC50 values of the reference drug (galanthamine) were 0.023 ± 0.15 and 0.047 ± 0.91 mM. Compound 1 could be a promising molecule against Alzheimer's disease.

Kombucha - An ancient fermented beverage with desired bioactivities: A narrowed review.

Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

Flavonoids as Sirtuin Modulators.

Sirtuins (SIRTs) are described as NAD+-dependent deacetylases, also known as class III histone deacetylases. So far, seven sirtuin genes (SIRTS 1-7) have been identified and characterized in mammals and are also known to occur in bacteria and eukaryotes. SIRTs are involved in various biological processes, including endocrine system, apoptosis, aging and longevity, diabetes, rheumatoid arthritis, obesity, inflammation, etc. Among them, the best-characterized one is SIRT1. Small molecules seem to be the most effective SIRT modulators. Flavonoids have been reported to possess many positive effects favorable for human health, while relatively less research has been reported so far on their functions as SIRT modulation mechanisms. In this regard, we aimed to focus on the modulatory effects of flavonoids on SIRTs as the most common secondary metabolites in natural products. Our literature survey covering the years from 2006 to 2021 pointed out that flavonoids frequently interact with SIRT1 and SIRT3, followed by SIRT6. It can also be concluded that some popular flavonoid derivatives, eg., resveratrol, quercetin, and catechin derivatives, came forward in terms of SIRT modulation.

Antiproliferative and cytotoxic activity of Geraniaceae plant extracts against five tumor cell lines.

AIM: To determine the antiproliferative and cytotoxic activities of Geranium and Erodium species against human cancer and noncancer cell lines, respectively. METHODS: Twenty-one species of Geranium and Erodium were extracted and screened against cancerous and noncancerous human cell lines. RESULTS: In a dose-response manner, G. glaberrimum, G. asphodeloides, E. brandianum and E. leucanthum were able, with variable potency, to inhibit cellular proliferation. Except for E. brandianum, all extracts induced cellular autophagy in tumor cells with similar levels to that of rapamycin; but, only E. brandianum induced cellular apoptosis, likely through Bcl2 and BAX protein expressions. DISCUSSION: This is the first study to report the potential antiproliferative effects of ethanol extracts of several Geraniaceae species.

Visual and linguistic semantic representations are aligned at the border of human visual cortex.

Semantic information in the human brain is organized into multiple networks, but the fine-grain relationships between them are poorly understood. In this study, we compared semantic maps obtained from two functional magnetic resonance imaging experiments in the same participants: one that used silent movies as stimuli and another that used narrative stories. Movies evoked activity from a network of modality-specific, semantically selective areas in visual cortex. Stories evoked activity from another network of semantically selective areas immediately anterior to visual cortex. Remarkably, the pattern of semantic selectivity in these two distinct networks corresponded along the boundary of visual cortex: for visual categories represented posterior to the boundary, the same categories were represented linguistically on the anterior side. These results suggest that these two networks are smoothly joined to form one contiguous map.

Evaluation of Healthy Lifestyle Behaviors in Psoriasis Patients.

OBJECTIVES: The purpose of our study was to compare healthy lifestyle behaviors between psoriasis patients and healthy controls. METHODS: This case-control study included 80 psoriasis patients and 80 sex- and age- matched healthy controls aged over 18. Participants completed the socio-demographic data form and the Health-Promoting Lifestyle Profile II (HPLP-II). The HPLP-II consists of 52 items and measures six components of health-promoting behavior outcomes: Nutrition, physical activity, health responsibility, spiritual growth, interpersonal relations, and stress management. Higher scores show that the individual applies the specified health behaviors at a high level. RESULTS: HPLP-II total scores were 128.3±21.1 in patient group and 132.5±22.3 in control group. Based on the scores, psoriasis patients showed a moderate level of health-promoting lifestyle, while controls showed a good level of health-promoting lifestyle. Spiritual growth score of patients (mean±SD = 25.6±4.9) was statistically lower than the controls (mean±SD = 27.3±4.5) (p=0.040). In addition, spiritual growth score and disease duration were negatively correlated in the patient group (r=-0.287, p=0.01). Furthermore, nutrition score of those with additional comorbidity was significantly higher than those with psoriasis alone in patient group (p=0.002). CONCLUSION: This is the first study to compare healthy lifestyle behaviors of psoriasis patients and healthy volunteers in Turkish population. The task of dermatologists is not only the medical treatment of psoriasis lesions but also questioning patients' lifestyle behaviors and supporting the development of healthy behaviors in patients.

Natural Products and Extracts as Xantine Oxidase Inhibitors - A Hope for Gout Disease?

Xanthine oxidase (EC 1.17.3.2) (XO) is one of the main enzymatic sources that create reactive oxygen species (ROS) in the living system. It is a dehydrogenase enzyme that performs electron transfer to nicotinamide adenine dinucleotide (NAD+), while oxidizing hypoxanthin, which is an intermediate compound in purine catabolism, first to xanthine and then to uric acid. XO turns into an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin turns into uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is crystallized, when present in high concentrations. Thus, XO inhibitors are one of the drug classes used against gout, a purine metabolism disease that causes urate crystal storage in the joint and its surroundings caused by hyperuricemia. Urate-lowering therapy includes XO inhibitors that reduce uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that obstruct uric acid synthesis through XO inhibition are allopurinol, febuxostat, and uricase. However, since the side effects, safety and tolerability problems of some current gout medications still exist, intensive research is ongoing to look for new, effective, and safer XO inhibitors of natural or synthetic origins for the treatment of the disease. In the present review, we aimed to assess in detail XO inhibitory capacities of pure natural compounds along with the extracts from plants and other natural sources via screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data pointed out to the fact that natural products, particularly phenolics such as flavonoids (quercetin, apigenin, and scutellarein), tannins (agrimoniin and ellagitannin), chalcones (melanoxethin), triterpenes (ginsenoside Rd and ursolic acid), stilbenes (resveratrol and piceatannol), alkaloids (berberin and palmatin) have a great potential for new XO inhibitors capable of use against gout disease. In addition, not only plants but other biological sources such as microfungi, macrofungi, lichens, insects (silk worms, ants, etc) seem to be the promising sources of novel XO inhibitors.

Spiro Heterocyclic Compounds as Potential Anti-Alzheimer Agents (Part 2): Their Metal Chelation Capacity, POM Analyses and DFT Studies.

BACKGROUND: One of the best methods to treat Alzheimer disease (AD) is through the effective use of cholinesterase inhibitors as vital drugs due to the identification of acetylcholine deficit in the AD patients. OBJECTIVE: The present study aims the investigation of spiro heterocyclic compounds as potential AD agents supported by their metal chelation capacity, POM analyses and DFT studies, respectively. METHODS: The cholinesterase inhibition and metal chelation ability were performed on ELISA microtiter assay. Whereas, the B3LYP method with 6-31+G(d,p) basis set was implemented to study HOMOLUMO energy calculations. The pharmacokinetic properties of the synthesized molecules were studied through Petra, Osiris and Molinspiration (POM). RESULTS: The six spiro (1-6) skeletons were tested for their inhibitory potential and metal-chelation capacity. Our findings revealed that the tested spiro skeletons exerted none or lower than 50% inhibition against both cholinesterases, while compound 4 proved to be the most active molecule with 57.21±0.89% of inhibition toward BChE. The spiro molecule 3 exhibited the highest metal-chelation capacity (9.12±5.26%). Molecular docking model for the most active molecule exhibited promising bindings with AChE and BChE's active site pertained to hydrophobic hydrogen bonds and positive ionizable interactions. The POM analyses gave the information about the flexibility at the site of coordination of spiro compounds (1-6). CONCLUSION: The screening of spirocompounds (1-6) against cholinesterases revealed that some of them show considerable potential to inhibit AChE and BChE. Herein, we propose that the spiro molecules after further derivatization could serve interesting AD inhibitor drugs.

Combined Structure and Ligand-Based Design of Selective Acetylcholinesterase Inhibitors.

Acetylcholinesterase is a prime target for therapeutic intervention in Alzheimer's disease. Acetylcholinesterase inhibitors (AChEIs) are used to improve cognitive abilities, playing therefore an important role in disease management. Drug repurposing screening has been performed on a corporate chemical library containing 11 353 compounds using a target fishing approach comprising three-dimensional (3D) shape similarity and pharmacophore modeling against an approved drug database, Drugbank. This initial screening identified 108 hits. Among them, eight molecules showed structural similarity to the known AChEI drug, pyridostigmine. Further structure-based screening using a pharmacophore-guided rescoring method identifies one more potential hit. Experimental evaluations of the identified hits sieve out a highly selective AChEI scaffold. Further lead optimization using a substructure search approach identifies 24 new potential hits. Three of the 24 compounds (compounds 10b, 10h, and 10i) based on a 6-(2-(pyrrolidin-1-yl)pyrimidin-4-yl)-thiazolo[3,2-a]pyrimidine scaffold showed highly promising AChE inhibition ability with IC50 values of 13.10 ± 0.53, 16.02 ± 0.46, and 6.22 ± 0.54 µM, respectively. Moreover, these compounds are highly selective toward AChE. Compound 10i shows AChE inhibitory activity similar to a known Food and Drug Administration (FDA)-approved drug, galantamine, but with even better selectivity. Interaction analysis reveals that hydrophobic and hydrogen-bonding interactions are the primary driving forces responsible for the observed high affinity of the compound with AChE.

Inhibition of Melanogenesis by Some Well-Known Polyphenolics: A Review.

Melanogenesis is simply defined as the production of melanin in melanosomes by melanocytes through a complex process. Melanin, a pigment derived from L-tyrosine, comes into two forms, namely eumelanin (brownish to black) and pheomelanin (red to yellow). Melanin synthesis starts via the hydroxylation of L-tyrosine to L-3,4-Dihydroxyphenylalanine (DOPA) catalyzed by the enzyme known as Tyrosinase (TYR), which triggers further conversion reaction to DOPAquinone and then to DOPAchrome. Additionally, this process is also related to two more proteins, i.e., oxygenase TYR-related Protein 1 (TYRP1), and Dopachrome Tautomerase TYRP2 (or DCT). However, TYR located in the melanosomal membrane still stands as the key enzyme to initiate the whole process of melanogenesis. Due to some deficits, melanogenesis may emerge as hypo- or hyperpigmentation in the skin. High production of melanin in melanocytes leads to hyperpigmentation- related skin disorders, including freckles, melasma, melanoma, etc., that may cause displeasure in personal appearance and reduce quality of life. Consequently, several melanogenesis inhibitors of synthetic and natural origins have been developed up to date, though most of them have been reported with serious side effects. For this reason, extensive research is still going on to find novel and more effective melanogenesis inhibitors with less side effects. In this sense, particularly flavonoids, catechins, and stilbenes from plants have been a hope to discover new inhibitors which gain significant attention from scientists. In this review, promising natural products effective in melanogenesis inhibition will be scrutinized.

Cholinesterase and Tyrosinase Inhibitory Potential and Antioxidant Capacity of Lysimachia verticillaris L. and Isolation of the Major Compounds.

OBJECTIVES: The scope of the present study was to specify the therapeutic potential for neurodegenerative diseases through evaluating cholinesterase and tyrosinase (TYR) inhibitory and antioxidant activity of Lysimachia verticillaris (LV), and to isolate the major compounds considering the most active fraction. MATERIALS AND METHODS: The methanol extract (ME) of LV and the chloroform, ethyl acetate (EtOAC), and aqueous fractions obtained from it were used for biological activity and isolation studies. The ME and all fractions were tested for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and TYR inhibitory and antioxidant potentials using ELISA microtiter assays. Seven major compounds were isolated from the active EtOAC fraction by semi-preparative high performance liquid chromatography. The structures of the compounds were elucidated by several spectroscopic methods. RESULTS: Marked AChE inhibitory activity was observed in the EtOAC fraction (6337±1.74%), BChE inhibitory activity in the ME and EtOAC fraction (85.84±3.01% and 83.82±3.93%), total phenol content in the EtOAC fraction (261.59±3.95 mg equivalent of gallic acid/1 g of extract) and total flavonoid contents in the EtOAC fraction (515.54±2.80 mg equivalent of quercetin/1 g of extract), and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and ferric-reducing antioxidant power values in the aqueous and EtOAC fractions (92.54±0.67%, 92.11±0.30%; 2.318±0.054, 2.224±0.091, respectively). Accordingly, the isolation studies were carried out on the EtOAC fractions. Compounds 1-7 (gallic acid, (+)-catechin, myricetin 3-O-arabinofuranoside, myricetin 3-O-α-rhamnopyranoside, quercetin 3-O-ß-glucopyranoside, quercetin 3-O-arabinofuranoside, and quercetin 3-O-α-rhamnopyranoside, respectively) were isolated from the active EtOAC fraction. CONCLUSION: LV may be a potential herbal source for treatment of neurodegenerative diseases based on its strong antioxidant activity and significant cholinesterase inhibition similar to that of the reference.

Reinvestigation of Herniaria glabra L. saponins and their biological activity.

Twelve undescribed triterpenoid pentacyclic glycosides, medicagenic acid (3-O-ß-D-glucuronopyranosyl-28-O-{[ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 3)]-4-O-acetyl-ß-D-fucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 3-O-ß-D-glucuronopyranosyl-28-O-{[α-L-rhamnopyranosyl-(1 → 2)]-[ß-D-apiofuranosyl-(1 → 3)]-4-O-acetyl-ß-D-fucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 3-O-ß-D-glucuronopyranosyl-28-O-{[α-L-rhamnopyranosyl-(1 → 2)]-3,4-O-diacetyl-ß-D-fucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 28-O-{[6-O-acetyl-ß-D-glucopyranosyl-(1 → 2)]-[2-O-acetyl-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 28-O-{[6-O-acetyl-ß-D-glucopyranosyl-(1 → 2)]-[3-O-acetyl-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 28-O-{[6-O-acetyl-ß-D-glucopyranosyl-(1 → 2)]-[4-O-acetyl-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 28-O-{[6-O-acetyl-ß-D-glucopyranosyl-(1 → 2)]-[ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid, 28-O-{[ß-D-glucopyranosyl-(1 → 2)]-[ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-12-ene-23,28-dioic acid), zanhic acid (3-O-ß-D-glucuronopyranosyl-28-O-{[ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 3)]-4-O-acetyl-ß-D-fucopyranosyl-(1→)}2ß,3ß,16α-trihydroxyolean-12-ene-23,28-dioic acid, 3-O-ß-D-glucuronopyranosyl-28-O-{[ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-ß-D-fucopyranosyl-(1→)}-2ß,3ß,16α-trihydroxyolean-12-ene-23,28-dioic acid), 29-hydroxy-medicagenic acid (3-O-ß-D-glucuronopyranosyl-28-O-{[ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 3)]-4-O-acetyl-ß-D-fucopyranosyl-(1→)}-2ß,3ß,29ß-trihydroxyolean-12-ene-23,28-dioic acid) and herniaric acid (28-O-{[6-O-acetyl-ß-D-glucopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-(1→)}-2ß,3ß-dihydroxyolean-18-ene-23,28-dioic acid) were isolated from the whole plant extract of Herniaria glabra L. (Caryophyllaceae), wild growing in the Ukraine. In addition, five known triterpenoid saponins; i.e. herniariasaponins 1, 4, 5, 6, and 7 were also isolated. Their structures were elucidated by HRESIMS, 1D and 2D NMR spectroscopy, as well as by comparison with the literature data. Twelve herniariasaponins, the purified crude extract, and the saponin fraction were evaluated in vitro for their xanthine oxidase, collagenase, elastase, and tyrosinase inhibitory activity. Moreover, herniariasaponins 4, 5, and 7 were screened for their cholinesterase inhibitory potential. As a result, no or low inhibition towards the mentioned enzymes was observed.

Yuccalechins A-C from the Yucca schidigera Roezl ex Ortgies Bark: Elucidation of the Relative and Absolute Configurations of Three New Spirobiflavonoids and Their Cholinesterase Inhibitory Activities.

The ethyl acetate fraction of the methanolic extract of Yucca schidigera Roezl ex Ortgies bark exhibited moderate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity (IC50 47.44 and 47.40 µg mL-1, respectively). Gel filtration on Sephadex LH-20 and further RP-C18 preparative HPLC of EtOAc fraction afforded 15 known and 3 new compounds, stereoisomers of larixinol. The structures of the isolated spirobiflavonoids 15, 26, and 29 were elucidated using 1D and 2D NMR and MS spectroscopic techniques. The relative configuration of isolated compounds was assigned based on coupling constants and ROESY (rotating-frame Overhauser spectroscopy) correlations along with applying the DP4+ probability method in case of ambiguous chiral centers. Determination of absolute configuration was performed by comparing calculated electronic circular dichroism (ECD) spectra with experimental ones. Compounds 26 and 29, obtained in sufficient amounts, were evaluated for activities against AChE and BChE, and they showed a weak inhibition only towards AChE (IC50 294.18 µM for 26, and 655.18 µM for 29). Furthermore, molecular docking simulations were performed to investigate the possible binding modes of 26 and 29 with AChE.