Phytochemical and bioactivities of promising flavonoid glycosides and their content from unmatured fruits of Vicia bungei with their bioactivity.

Flavonoids have extensive biological qualities that support human health. A molecular networking strategy produced representative networks despite mass fragmentation of spectra of untargeted data-dependent acquisition approach to target flavonoid glycosides from Vicia bungei by using UHPLC-MS guided isolation. Using contemporary methods, seven chemicals were extracted and identified. Antioxidative and anti-inflammatory effects of these isolates were assessed in vitro on free radicals and inflammatory mediators, cytokines, enzymatic proteins. Two active compounds, apigenin 6-C-ß-D-galactopyranosyl-8-C-ß-D-xylopyranoside, and sphaerobioside, were further assessed for their binding affinity to target protein in in silico study. The molecular mechanism of sphaerobioside was found to involve suppression of LPS-stimulated inflammation by NF-κB inactivation by inhibiting nuclear translocation of p65 and prevention of phosphorylation of κB inhibitor α (IκBα) and IκB kinase (IKKα/ß). Furthermore, an analytical method was successfully established and employed to quantify the total extract using these seven chemicals present in this plant as markers.

Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease.

INTRODUCTION: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure. METHODS: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls. RESULTS: Circulating amyloid beta (Aß), tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, p-tauS235, ubiquitin, and lysosomal-associated membrane protein 1-positive EVs distinguished AD samples. p-tau181, p-tau217, p-tauS235, and ubiquitin-positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p-tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p-tauS235. DISCUSSION: This nFC-based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC-based measurements in larger populations and comparison to "gold standard" biomarkers is an exciting next step for developing AD diagnostic tools. HIGHLIGHTS: Extracellular vesicles represent promising biomarkers of Alzheimer's disease (AD) that can be measured in the peripheral circulation. This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples. Multiple markers including amyloid beta, tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, and p-tauS235 accurately distinguished AD samples from healthy controls. Future studies should expand blood and cerebrospinal fluid-based EV biomarker development using nanoflow cytometry approaches.

Molecular Networking and Bioassay-Guided Preparation and Separation of Active Extract and Constituents from Vicia tenuifolia Roth.

Molecular networking drove the selection of material from V. tenuifolia organs that targeted active flavonoid glycosides. To optimize the extraction process, the flowers of V. tenuifolia were used to produce an anti-inflammatory extract. The effects of variables-organic solvent ratio; extraction time; and temperature-were investigated by the response of anti-inflammatory activity. Bioactivities-guided experiments helped identify fractions with high total phenolic and flavonoid content as well as antioxidant potential. Furthermore, one new compound (1), 19 first isolated together, and two known compounds were obtained and identified from the active fraction of this plant. Among them, compounds (15 and 22) were first reported for nuclear magnetic resonance (NMR) data from this study. All the isolates were evaluated for their anti-inflammatory capacity throughout, modulating nitric oxide (NO), interleukin (IL)-1ß, and IL-8 production. Active compounds were further investigated for their regulation and binding affinity to the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins by Western blot and in silico approaches, respectively. The findings of this study suggested that the developed extract method, active fraction, and pure components should be further investigated as promising candidates for treating inflammation and oxidation.

Molecular networking-guided isolation strategy of a new C-glycosyl flavone rotamer from Stellaria alsine and evaluation of anti-inflammatory and antioxidant activities.

INTRODUCTION: Stellaria alsine has traditionally been used as both a famine relief food and an alternative medicine in East Asia. Modern pharmacological studies have revealed that S. alsine has various biological effects such as anticancer, anti-hepatoma, anti-inflammatory, and antioxidative effects. However, the anti-inflammatory properties of chemical constituents derived from this plant have not been studied well. OBJECTIVES: To identify potential therapeutic candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD). METHODS: The distribution of chemical compounds was investigated by Global Natural Product Social (GNPS)-based molecular networking (MN) analysis using UPLC-Orbitrap tandem mass spectrometry. The anti-inflammatory and antioxidative effects of S. alsine extracts and fractions were evaluated by measuring interleukin (IL)-8 and reactive oxygen species (ROS) productions. RESULTS: The active EA layer of S. alsine showed the highest percentage of major compounds by feature-based molecular networking. The top candidate structures of EA fraction were rapidly annotated as flavone C- or O-glycosides via an advanced analysis tool, Network Annotation Propagation (NAP). With the GNPS molecular networking-guided isolation strategy, a new C-glycosyl flavone rotamer (1) was isolated. The structures of the major (1a) and minor (1b) rotational isomers were determined by extensive NMR analysis and MS/MS fragmentation. Finally, the anti-inflammatory activity of 1 was predicted by molecular docking simulations with IL-8 protein. CONCLUSION: These results suggested that the compound 1 is a potential therapeutic candidate for inflammatory bowel disease (IBD).

Anti-inflammatory activity of caffeic acid derivatives from Ilex rotunda.

Ilex rotunda Thunb. has been used in traditional medicine for treating rheumatoid arthritis, relieving pain and indigestion. In the present study, we isolated three new caffeic acid benzyl ester (CABE) analogs (1-3) along with eight known compounds (4-11) from the extract of I. rotunda. The absolute configuration of α-hydoxycarboxylic acid in 1 was assigned with the phenylglycine methyl ester (PGME) method. We further investigated their anti-inflammatory activities in lipopolysaccharide (LPS)-induced macrophages (RAW 264.7) cells. Among them, compounds 2-4, 7, 8, 10, and 11 suppressed the production of nitric oxide (NO), pro-inflammatory mediators. It was additionally confirmed that the anti-inflammatory effect of active compound 2 was through significant suppression of cytokines, including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and IL-8 in LPS-stimulated RAW 264.7 cells and colon epithelial (HT-29) cells. Western blot analysis revealed that compound 2 decreased the LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated extracellular regulated kinase (pERK)1/2. The following molecular docking simulations showed the significant interactions of compound 2 with the iNOS protein. These results suggested that the compound 2 can be used as potential candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD).

Comparison of Behavior-Related Features in the MMSE Sentence in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

Background: Despite the ubiquity of cognitive assessments using the MMSE, there has been little investigation of currently unscored features of the MMSE sentence item relevant to behavior and language in patients with behavioral variant Frontotemporal Dementia (bvFTD) and Alzheimer's disease (AD). Objective: To describe and compare the unscored content and grammar elements of the MMSE sentence item in patients with bvFTD and AD. Methods: Categorization of predefined content and grammar elements of the MMSE sentence was performed by two blinded raters in patients with bvFTD (n = 74) and AD (n = 84). Chi-square and ANCOVAs were conducted to identify differences between the diagnostic groups. A multinomial logistic regression analysis was conducted to determine whether these features aid in the prediction of diagnosis of bvFTD or AD. Results: A higher proportion of patients with bvFTD wrote sentences addressed to the examiner (22.7% vs. 4.7%, X 2 = 11.272, p = 0.001) and about interpersonal relationships (35.3% vs. 16.0%, X 2 = 10.139, p = 0.017) in comparison to those with AD. The number of words written was lower in patients with AD and was positively correlated with lower total MMSE scores in AD but not in bvFTD (AD: r = 0.370, p < 0.001; FTD: r = 0.209, p = 0.07). Assessment of the MMSE sentence content and grammar variables did not add to the prediction bvFTD or AD diagnosis beyond the variance explained by age and total MoCA score. Conclusions: Patients with bvFTD and AD showed differences in aspects of the content of the written MMSE sentence item, though these differences did not aid in the diagnosis prediction.