Inhibitory activity of chemical constituents from Arenaria serpyllifolia on nitric oxide production.

Five new compounds, including one new xanthone, 1-hydroxy-5-methoxyxanthone 6-O-ß-D-glucopyranoside (1), one new lignan, 3-(ß-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-acetoxypropyl)-7-methoxy-(2R,3S)-dihydrobenzofuran (2), and three new γ-pyrones, japonicumone A 4'-O-ß-D-glucopyranoside (3), japonicumone B 3'-O-ß-D-glucopyranoside (4), and japonicumone B 4'-O-ß-D-glucopyranoside (5), together with eight known compounds (6-13) were isolated from the whole plants of Arenaria serpyllifolia. Their structures were elucidated on the basis of extensive spectroscopic analysis (UV, IR, HRESIMS, 1D- and 2D-NMR, and CD) as well as chemical methods. The isolated compounds were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages. Compounds 1-5, sacranoside A (9), and pedunculoside (13) showed potential nitric oxide inhibitory activities with IC50 values ranging from 14.92 µM to 52.23 µM.

Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals.

Transcriptional regulation lies at the core of the circadian clockwork, but how the clock-related transcription machinery controls the circadian phase is not understood. Here, we show both in human cells and in mice that RuvB-like ATPase 2 (RUVBL2) interacts with other known clock proteins on chromatin to regulate the circadian phase. Pharmacological perturbation of RUVBL2 with the adenosine analog compound cordycepin resulted in a rapid-onset 12-hour clock phase-shift phenotype at human cell, mouse tissue, and whole-animal live imaging levels. Using simple peripheral injection treatment, we found that cordycepin penetrated the blood-brain barrier and caused rapid entrainment of the circadian phase, facilitating reduced duration of recovery in a mouse jet-lag model. We solved a crystal structure for human RUVBL2 in complex with a physiological metabolite of cordycepin, and biochemical assays showed that cordycepin treatment caused disassembly of an interaction between RUVBL2 and the core clock component BMAL1. Moreover, we showed with spike-in ChIP-seq analysis and binding assays that cordycepin treatment caused disassembly of the circadian super-complex, which normally resides at E-box chromatin loci such as PER1, PER2, DBP, and NR1D1 Mathematical modeling supported that the observed type 0 phase shifts resulted from derepression of E-box clock gene transcription.

Polygalins D-G, four new flavonol glycosides from the aerial parts of Polygala sibirica L. (Polygalaceae).

Four new flavonol glycosides (1-4), polygalins D-G, together with 12 known flavonoids (5-16) were isolated from the aerial parts of Polygala sibirica L. The chemical structures of these compounds were characterised by NMR and ESI-MS spectroscopic data and acid hydrolysis results. This report is a continuous research work on the systematic chemical investigations of plants of the genus Polygala in our laboratory.

A rapid and sensitive HPLC-MS/MS analysis and preliminary pharmacokinetic characterization of sibiricaxanthone F in rats.

A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantifying sibiricaxanthone F (SF) in rat plasma following oral and intravenous dosings. After addition of the internal standard (IS) kaempferol and the antioxidant, 20% ascorbic acid, plasma samples were precipitated with acetonitrile and separated on an Aglient Zorbax XDB-C(18) column (50 mm × 4.6mm I.D., 2.1 µm) with gradient acetonitrile and water (both containing 0.01% formic acid) as the mobile phase. The detection was performed on a Sciex API 4000 LC-MS/MS with electrospray ionization (ESI) inlet in the negative multiple reaction monitoring (MRM) mode. Good linearity was achieved over the concentration range of 0.5-500.0ng/mL (r>0.996). Intra- and inter-day precisions were less than 7.60%, and accuracy ranged from 97.18% to 99.84%. The lower limit of quantification for SF was 0.5 ng/mL, and analytes were stable under various conditions (during freeze-thaw, at room temperature and under deep-freeze conditions). This validated method was successfully applied to the preliminary pharmacokinetic study of SF in rats for the first time, and the absolute bioavailability of SF was found to be only 0.22 ± 0.15%.