title: 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)-3beta,7,4'-trihydroxy-5-methoxy-8-(gamma,gamma-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 microM, respectively, compared with quercetin (IC50 7.73 microM). In the HRAR assay, most of the prenylated flavonoids tested showed marked inhibitory activity compared with quercetin (IC50 2.54 microM). In particular, all tested prenylated flavonols, such as desmethylanhydroicaritin (1, IC50 0.45 microM), 8-lavandulylkaempferol (2, IC50 0.79 microM) and kushenol C (3, IC50 0.85 microM), as well as a prenylated chalcone, kuraridin (5, IC50 0.27 microM), and a prenylated flavanone, (2S)-7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylally)-flavanone (12, IC50 0.37 microM), showed significant inhibitory activities compared with the potent AR inhibitor epalrestat (IC50 0.28 microM). Interestingly, prenylated flavonoids 1 (IC50 104.3 microg mL(-1)), 2 (IC50 132.1 microg mL(-1)), 3 (IC50 84.6 microg mL(-1)) and 11 (IC50 261.0 microg mL(-1)), which harbour a 3-hydroxyl group, also possessed good inhibitory activity toward AGE formation compared with the positive control aminoguanidine (IC50 115.7 microg mL(-1)). Thus, S. flavescens and its prenylated flavonoids inhibit the processes that underlie diabetic complications and related diseases and may therefore have therapeutic benefit.
authors: Division of Food Science and Biotechnology, Pukyong National University, Busan 608-737, South Korea.
authors: Hyun Ah
authors: HA
authors: Jung
authors: Na Young
authors: NY
authors: Yoon
authors: Sam Sik
authors: SS
authors: Kang
authors: Yeong Sik
authors: YS
authors: Kim
authors: Jae Sue
authors: JS
authors: Choi
mesh_terms: D000449:Aldehyde Reductase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D047188:Chalcones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D047309:Flavones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008519:Medicine, Traditional; D010936:Plant Extracts / Q000494:pharmacology; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012236:Rhodanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D029909:Sophora / Q000737:chemistry*; D053778:Thiazolidines / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D047188:Chalcones; D047309:Flavones; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D006146:Guanidines; D010936:Plant Extracts; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D011794:Quercetin; D000449:Aldehyde Reductase; C004479:pimagedine