Background: The main characteristic of Diabetes type II is the impaired activation of intracellular
mechanisms triggered by the action of insulin. PTP1b is a Protein Tyrosine Phosphatase that
dephosphorylates insulin receptor causing its desensitization. Since inhibition of PTP1b may prolong
insulin receptor activity, PTP1b has become a drug target for the treatment of Diabetes II. Although a
number of inhibitors have been synthesized during the last decades, the research still continues for the
development of more effective and selective compounds. Moreover, several constituents of plants and
edible algae with PTP1b inhibitory action have been found, adding this extra activity at the pallet of
properties of the specific natural products.
Objective: Sideritis L. (Lamiaceae) is a herbal plant growing around the Mediterranean sea which is included
in the Mediterranean diet for centuries. The present study is the continuation of a previous work
where the antioxidant and anti-inflammatory activities of the components of Sideritis L. were evaluated
and aimed to investigate the potential of some sideritis’s components to act as PTP1b inhibitors, thus
exhibiting the beneficial effect in the treatment of diabetes II.
Methods: Docking analysis was done to predict PTP1b inhibitory action. Human recombinant PTP1b
enzyme was used for the evaluation of the PTP1b inhibitory action, while inhibition of the human LAR
and human T-cell PTP was tested for the estimation of the selectivity of the compounds.
Conclusion: Docking analysis effectively predicted inhibition and mode of inhibitory action. According
to the experimental results, four of the components exhibited PTP1b inhibitory action. The most active
ones were acetoside, which acted as a competitive inhibitor, with an IC50 of 4 µM and lavandufolioside,
which acted as an uncompetitive inhibitor, with an IC50 of 9.3 µM. All four compounds exhibited increased
selectivity against PTP1b.