Menisperdaurines A-W, structurally diverse isoquinoline alkaloids from Menispermum dauricum and their dopamine D1 receptor activities.

A total of 33 structurally diverse isoquinoline alkaloids were isolated from the rhizomes of Menispermum dauricum, including seventeen benzylisoquinoline analogues (menisperdaurines A-Q, 1-17), five protoberberine analogues (menisperdaurines R-V, 18-22), a quaternary phenanthrene alkaloid (menisperdaurine W, 23) and ten known compounds (24-33). Compound structures, including absolute configurations, were determined by extensive spectroscopic methods, quantum chemical calculations of chemical shifts, and calculated and experimental electronic circular dichroism (ECD) data. Compounds 1-5 were glycosidic benzylisoquinolines with glucose moieties attached at the C-12 position. Compound 8 was the first example that was isolated from the rhizomes of Menispermum dauricum, benzylisoquinoline and an aromatic unit connected by a sugar bridge. Compounds were evaluated for their inhibitory effects on the dopamine D1 receptor. Compounds 1, 8, 21, 24 and 29 showed potent D1 antagonistic activities, with IC50 values ranging from 1.0 to 4.5 µM. Compound 1 exhibited the highest antagonistic activity with an IC50 value of 1.0 ± 0.2 µM.

Isoquinoline alkaloid dimers with dopamine D1 receptor activities from Menispermum dauricum DC.

A phytochemical investigation on chemical constituents from the rhizomes of Menispermum dauricum DC. identified eight undescribed dimeric alkaloids with structurally diverse monomeric isoquinoline. Alkaloid structures were elucidated by a combination of spectroscopic data analyses and time-dependent density functional theory (TDDFT) ECD calculation. The isolates were evaluated for inhibitory effect on dopamine D1 receptor and compound 1 exhibited potent D1 receptor antagonistic activity with an IC50 value of 8.4 ± 2.0 µM.

Complete genome sequence of the bacterium Ketogulonicigenium vulgare Y25.

Ketogulonicigenium vulgare is characterized by the efficient production of 2KGA from L-sorbose. Ketogulonicigenium vulgare Y25 is known as a 2-keto-L-gulonic acid-producing strain in the vitamin C industry. Here we report the finished, annotated genome sequence of Ketogulonicigenium vulgare Y25.

Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10.

Toll-like receptor (TLR)-10 remains an orphan receptor without well-characterized ligands or functions. Here, we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting that dsRNA is a ligand of TLR10. Recognition of dsRNA by TLR10 activates recruitment of myeloid differentiation primary response gene 88 for signal transduction and suppression of interferon regulatory factor-7 dependent type I IFN production. We also demonstrate crosstalk between TLR10 and TLR3, as they compete with each other for dsRNA binding. Our results suggest for the first time that dsRNA is a ligand for TLR10 and propose novel dual functions of TLR10 in regulating IFN signaling: first, recognition of dsRNA as a nucleotide-sensing receptor and second, sequestration of dsRNA from TLR3 to inhibit TLR3 signaling in response to dsRNA stimulation.