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

• Published in: Pharmaceutics 2023-04, Vol.15 (4), p.1239
• Main Authors: Kim, Hyo-Seon, Lee, Dahae, Seo, Young-Hye, Ryu, Seung-Mok, Lee, A-Yeong, Moon, Byeong-Cheol, Kim, Wook-Jin, Kang, Ki-Sung, Lee, Jun
• Format: Article
• Language: English
• Subjects: Angelica reflexa; Chromatography; diabetes; Glucose; glucose-stimulated insulin secretion; Herbal medicine; Hyperglycemia; Insulin; marmesinin; Medicine; Metabolism; Ostericum koreanum
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15041239

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.