Diabetes mellitus describes a group of metabolic disorders characterized by chronic
hyperglycemia resulting either from a deficiency of insulin, or decreased ability
to transduce the insulin signal, or both. People with diabetes are at great risk of
developing long-term complications including neuropathy, retinopathy, nephropathy
and vascular diseases. Aldose reductase (AR, ALR2, E.C. 1.1.1.21, alditol//NADP+ oxidoreductase) of the polyol metabolic pathway was first found to be implicated
in the etiology of the secondary complications of diabetes. Inhibition of the enzyme
aldose reductase seems to be a good approach in the prevention of these diabetic complications.
There have been a number of reports about ALR2 inhibitors obtained from natural sources.
In vitro testing of the extracts and bioactive constituents of Centaurea phyllocephala Boiss., a plant that is reputed in certain parts of the Middle East to have an antidiabetic
effect, on aldose reductase was carried out. Then the IC50 for the most efficient of them was calculated. The crude extracts of the aerial parts
of C. phyllocephala afforded the dehydromelitensine derivatives, 8α-(3,4-dihydroxy-2-methylene-butanoyloxy)
(1) and 8α-(3-hydroxy-4-acetoxy-2-methylene-butanoyloxy) (2), one eudesmane derivative, malacitanolide (3), p-OH-benzoic acid (4), three flavonoids eupatorin (5), cirsilineol (6) and 5-hydroxy,6,7,3',4'-tetramethoxyflavone (7) and β-sitosterol (8). The polar extract of C. phyllocephala exhibited strong aldose reductase inhibition even at lower concentrations: for concentration
9.8µg/ml the %Inhibition (±SD) was 61(±1.4). From the tested compounds, 5 [IC50: 11(±0.775)µM] and 6 [IC50: 12(±0.983)µM] exhibited the best inhibitory activity.
