Ratanhiaphenol III from Ratanhiae radix is a PTP1B inhibitor.
The inhibition of protein tyrosine phosphatase 1B (PTP1B) is considered a valid strategy to combat insulin resistance and type II diabetes. We show here that a dichloromethane extract of Ratanhiae radix ( RR_EX) dose-dependently inhibits human recombinant PTP1B in vitro and enhances insulin-stimulated glucose uptake in murine myocytes. By determination of the PTP1B inhibiting potential of 11 recently isolated lignan derivatives from RR_EX, the observed activity of the extract could be partly assigned to ratanhiaphenol III. This compound inhibited PTP1B in vitro with an IC (50) of 20.2 µM and dose-dependently increased insulin receptor phosphorylation as well as insulin-stimulated glucose uptake in cultured myotubes. This is the first report to reveal an antidiabetic potential for a constituent of rhatany root, traditionally used against inflammatory disorders, by showing its capability of inhibiting PTP1B.
Department of Pharmacognosy, University of Vienna, Vienna, Austria.
Elke H
EH
Heiss
Lisa
L
Baumgartner
Stefan
S
Schwaiger
Raul Jimenez
RJ
Heredia
Atanas G
AG
Atanasov
Judith M
JM
Rollinger
Hermann
H
Stuppner
Verena M
VM
Dirsch
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D031326:Krameriaceae / Q000737:chemistry*; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D032342:Muscle Cells / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*
D001572:Benzofurans; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D017705:Lignans; D028321:Plant Preparations; C575484:ratanhiaphenol III; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose