Inhibitory activities of prenylated flavonoids from Sophora flavescens against aldose reductase and generation of advanced glycation endproducts

Abstract

Important targets for the prevention and treatment of diabetic complications include aldose reductase (AR) inhibitors (ARIs) and inhibitors of advanced glycation endproduct (AGE) formation. Here we evaluate the inhibitory activities of prenylated flavonoids isolated from Sophora flavescens, a traditional herbal medicine, on rat lens AR (RLAR), human recombinant AR (HRAR) and AGE formation. Among the tested compounds, two prenylated chalcones — desmethylanhydroicaritin (1) and 8-lavandulylkaempferol (2) — along with five prenylated flavanones — kurarinol (8), kurarinone (9), (2S)-2′-methoxykurarinone (10), (2S)-3β,7,4′-trihydroxy-5-methoxy-8-(γ,γ-dimethylally)-flavanone (11), and kushenol E (13) were potent inhibitors of RLAR, with IC50 values of 0.95, 3.80, 2.13, 2.99, 3.77, 3.63 and 7.74 μM, respectively, compared with quercetin (IC50 7.73 μM). In the HRAR assay, most of the prenylated flavonoids tested showed marked inhibitory activity compared with quercetin (IC50 2.54 μM). In particular, all tested prenylated flavonols, such as desmethylanhydroicaritin (1, IC50 0.45 μM), 8-lavandulylkaempferol (2, IC50 0.79 μM) and kushenol C (3, IC50 0.85 μM), as well as a prenylated chalcone, kuraridin (5, IC50 0.27 μM), and a prenylated flavanone, (2S)-7,4′-dihydroxy-5-methoxy-8-(γ,γ-dimethylally)-flavanone (12, IC50 0.37 μM), showed significant inhibitory activities compared with the potent AR inhibitor epalrestat (IC50 0.28 μM). Interestingly, prenylated flavonoids 1 (IC50 104.3 μgmL−1), 2 (IC50 132.1 μgmL−1), 3 (IC50 84.6 μgmL−1) and 11 (IC50 261.0 μgmL−1), which harbour a 3-hydroxyl group, also possessed good inhibitory activity toward AGE formation compared with the positive control aminoguanidine (IC50 115.7 μgmL−1). Thus, S. flavescens and its prenylated flavonoids inhibit the processes that underlie diabetic complications and related diseases and may therefore have therapeutic benefit.