scopoletin and scopolin

Artemisia iwayomogi has been used as a folk medicine for treating various diseases including inflammatory and immune-related diseases. Scopoletin (1) and scopolin (2) were isolated from this species. Scopoletin (1) showed more potent peroxyl radical-scavenging capacity, reducing capacity, and cellular antioxidant capacity compared to scopolin (2). The inhibitory effect of 1 on the receptor activator of nuclear factor κB ligand-induced osteoclastic differentiation of RAW 264.7 macrophage cells was also more potent than that of 2. The production of general reactive oxygen species (ROS) and superoxide anions during differentiation of preosteoclastic RAW 264.7 cells into osteoclasts was attenuated by compounds 1 and 2. These findings indicate that the suppressive effects of 1 and 2 on the differentiation of preosteoclastic RAW 264.7 cells is partially due to their intracellular antioxidant capacity, as they can scavenge ROS and play an important signaling role in the differentiation process.

Topics: Animals; Antioxidants; Artemisia; Cell Differentiation; Coumarins; Glucosides; Hydrogen Peroxide; Korea; Macrophages; Mice; Molecular Structure; Osteoclasts; Reactive Oxygen Species; Scopoletin

For the targeting selection of acetylcholinesterase (AChE) inhibitors from natural sources we generated a structure-based pharmacophore model utilizing an in silico filtering experiment for the discovery of promising candidates out of a 3D multiconformational database consisting of more than 110,000 natural products. In our study, scopoletin (1) and its glucoside scopolin (2) emerged as potential AChE inhibitors by the virtual screening procedure. They were isolated by different chromatographic methods from the medicinal plant Scopolia carniolica Jaqc. and tested in an enzyme assay using Ellman's reagent. They showed moderate, but significant, dose-dependent and long-lasting inhibitory activities. In the in vivo experiments (icv application of 2 micromol) 1 and 2 increased the extracellular acetylcholine (ACh) concentration in rat brain to about 170% and 300% compared to basal release, respectively. At the same concentration, the positive control galanthamine increased the ACh concentration to about the same level as 1. These are the first in vivo results indicating an effect of coumarins on brain ACh.

Topics: Acetylcholine; Acetylcholinesterase; Animals; Brain; Cholinesterase Inhibitors; Coumarins; Glucosides; Injections, Intraventricular; Models, Molecular; Molecular Structure; Plant Extracts; Quantitative Structure-Activity Relationship; Rats; Scopoletin; Scopolia