title: Excretion of tectoridin metabolites in rat urine and bile orally administrated at different dosages and their inhibitory activity against aldose reductase.
abstract: This study investigated the urinary and biliary excretion of tectoridin, a major active isoflavonoid found in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Using UHPLC/Q-TOFMS, seven glucuronides and/or sulfated metabolites and four Phase I metabolites were simultaneously quantified in rat urine after oral administration of tectoridin at 100 and 200 mg/kg. Over a 72-h period, 14.2% and 14.7% of the tectoridin were excreted as eleven metabolites in urine, among which, two major metabolites tectorigenin-7-O-β-D-glucuronide (Te-7G) and tectorigenin accounted for 5.5-5.5% and 4.3-4.4%. Furthermore, the cumulative excretion of four glucuronides and sulfated metabolites in bile accounted for 7.3% and 3.9% of the dose within 60 h, among which, Te-7G and tectorigenin-7-O-glucuronide-4'-O-sulfate (Te-7G-4'S) accounted for 2.3-3.0% and 1.4-3.9%, respectively. The results indicate that the urine was the primary elimination route, and glucuronidation after deglycosylation at C-7 position was the major metabolic pathway of tectoridin in vivo. Moreover, the inhibitory activities of tectoridin and its five metabolites on rat lens aldose reductase were confirmed (IC₅₀: 1.4-15.5 μM), whereas irisolidone-7-O-glucuronide (Ir-7G) and irisolidone showed little activity.
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Qu
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China. Electronic address: wangtao@tjutcm.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: yuandan_kampo@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yuan
mesh_terms: D000284:Administration, Oral; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001646:Bile / Q000737:chemistry; D035264:Flowers / Q000737:chemistry; D027621:Iridaceae / Q000737:chemistry; D007529:Isoflavones / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D007908:Lens, Crystalline / Q000201:enzymology; D008297:Male; D029908:Pueraria / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry
chemical_list: D007529:Isoflavones; C120040:tectoridin; D000449:Aldehyde Reductase
keywords: Aldose reductase inhibitory activity; Conjugate metabolites; Excretion; Tectoridin; UHPLC/Q-TOF MS