Inhibitory activity of coumarins from Artemisia capillaris against advanced glycation endproduct formation

Arch Pharm Res. 2012 Jun;35(6):1021-35. doi: 10.1007/s12272-012-0610-0. Epub 2012 Jun 30.

Abstract

Since glycation can lead to the onset of diabetic complications due to chronic hyperglycemia, several indigenous Artemisia species were evaluated as potential inhibitors of advanced glycation endproducts (AGE). Among them, the Artemisia capillaris plant demonstrated the highest AGE inhibitory activity. Repeated column chromatography was performed to isolate a new acylated flavonoid glycoside, acacetin-7-O-(6″-O-acetyl)-β-D-glucopyranosyl-(1→2)[α-L-rhamnopyranosyl]-(1→6)-β-D-glucopyranoside, along with 11 known flavonoids (acacetin-7-O-β-D-glucopyranosyl-(1→2)[α-L-rhamnopyranosyl]-(1→6)-β-D-glucopyranoside, linarin, quercetin, hyperoside, isorhamnetin, isorhamnetin 3-galactoside, isorhamnetin 3-glucoside, isorhamnetin 3-arabinoside, isorhamnetin 3-robinobioside, arcapillin, and cirsilineol), six coumarins (umbelliferone, esculetin, scopoletin, scopolin, isoscopolin, and scoparone), and two phenolic derivatives (4,5-di-O-caffeoylquinic acid and chlorogenic acid). In determining the structure-activity relationship (SAR), it was found that the presence and position of hydroxyl group of test coumarins (coumarin, esculin, isoscopoletin, daphnetin, 4-methylcoumarin, and six isolated coumarins) may play a crucial role in AGE inhibition. A free hydroxyl group at C-7 and a glucosyl group instead of a methoxyl group at C-6 are two important parameters for the inhibitory potential of coumarins on AGE formation. A. capillaris and five key AGE inhibitors, including 4,5-di-Ocaffeoylquinic acid, umbelliferone, esculetin, esculin, and scopoletin, were identified as potential candidates for use as therapeutic or preventive agents for diabetic complications and oxidative stress-related diseases. We understand this to be the first detailed study on the SAR of coumarins in AGE inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors
  • Aldehyde Reductase / metabolism
  • Animals
  • Artemisia* / chemistry
  • Coumarins / chemistry
  • Coumarins / isolation & purification
  • Coumarins / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Free Radical Scavengers / pharmacology
  • Glycation End Products, Advanced / metabolism*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / enzymology
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Coumarins
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • Plant Extracts
  • Aldehyde Reductase