Chemical Constituents from the Roots of That Improve Glucose-Stimulated Insulin Secretion by Regulating Pancreatic β-Cell Metabolism.

The aim of this study was to discover bioactive constituents of that improve glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. Herein, three new compounds, namely, koseonolin A (), koseonolin B (), and isohydroxylomatin (), along with 28 compounds (-) were isolated from the roots of . by chromatographic methods. The chemical structures of new compounds (-) were elucidated through spectroscopic/spectrometric methods such as NMR and HRESIMS. In particular, the absolute configuration of the new compounds ( and ) was performed by electronic circular dichroism (ECD) studies. The effects of the root extract of . (KH2E) and isolated compounds (-) on GSIS were detected by GSIS assay, ADP/ATP ratio assay, and Western blot assay. We observed that KH2E enhanced GSIS. Among the compounds -, isohydroxylomatin (), (-)-marmesin (), and marmesinin () increased GSIS. In particular, marmesinin () was the most effective; this effect was superior to treatment with gliclazide. GSI values were: 13.21 ± 0.12 and 7.02 ± 0.32 for marmesinin () and gliclazide at a same concentration of 10 μM, respectively. Gliclazide is often performed in patients with type 2 diabetes (T2D). KH2E and marmesinin () enhanced the protein expressions associated with pancreatic β-cell metabolism such as peroxisome proliferator-activated receptor γ, pancreatic and duodenal homeobox 1, and insulin receptor substrate-2. The effect of marmesinin () on GSIS was improved by an L-type Ca channel agonist and K+ channel blocker and was inhibited by an L-type Ca channel blocker and K channel activator. Marmesinin () may improve hyperglycemia by enhancing GSIS in pancreatic β-cells. Thus, marmesinin () may have potential use in developing novel anti-T2D therapy. These findings promote the potential application of marmesinin () toward the management of hyperglycemia in T2D.