Inhibitory activity of extracts and bioactive constituents of Centaurea phyllocephala Boiss. (Asteraceae) on aldose reductase in vitro

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.