Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV

J Agric Food Chem. 2014 Jul 2;62(26):6147-58. doi: 10.1021/jf500639f. Epub 2014 Jun 13.

Abstract

Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis), and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims were to characterize and examine extracts from greenhouse-grown or commercially purchased herbs for their ability to inhibit dipeptidyl peptidase IV (DPP-IV) and protein tyrosine phosphatase 1B (PTP1B), enzymes that play a role in insulin secretion and insulin signaling, respectively. Greenhouse herbs contained more polyphenols (302.7-430.1 μg of gallic acid equivalents/mg of dry weight of extract (DWE)) and flavonoids (370.1-661.4 μg of rutin equivalents/mg of DWE) compared to the equivalent commercial herbs. Greenhouse rosemary, Mexican oregano, and marjoram extracts were the best inhibitors of DPP-IV (IC₅₀=16, 29, and 59 μM, respectively). Commercial rosemary, Mexican oregano, and marjoram were the best inhibitors of PTP1B (32.4-40.9% at 500 μM). The phytochemicals eriodictyol, naringenin, hispidulin, cirsimaritin, and carnosol were identified by LC-ESI-MS as being present in greenhouse-grown Mexican oregano and rosemary. Computational modeling indicated that hispidulin, carnosol, and eriodictyol would have the best binding affinities for DPP-IV. Biochemically, the best inhibitors of DPP-IV were cirsimaritin (IC₅₀=0.43±0.07 μM), hispidulin (IC₅₀=0.49±0.06 μM), and naringenin (IC₅₀=2.5±0.29 μM). Overall, herbs contain several flavonoids that inhibit DPP-IV and should be investigated further regarding their potential in diabetes management.

Keywords: DPP-IV; PTP1B; hispidulin; marjoram; oregano; rosemary; type 2 diabetes mellitus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Crops, Agricultural / chemistry
  • Crops, Agricultural / economics
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology
  • Dipeptidyl-Peptidase IV Inhibitors / analysis
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / isolation & purification*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Drug Discovery
  • Humans
  • Ligands
  • Lippia / chemistry*
  • Molecular Docking Simulation
  • Molecular Structure
  • Origanum / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Leaves / chemistry*
  • Protein Kinase Inhibitors / analysis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / isolation & purification*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Rosmarinus / chemistry*
  • Sus scrofa

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Ligands
  • Plant Extracts
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1