Isolation of Cholinesterase-Inhibiting Flavonoids from Morus lhou = 뽕나무로부터 분리한 플라보노이드 화합물들의 콜린에스터레이즈 저해제 활성

Abstract

Cholinesterases are key enzymes that play important roles in cholinergic transmission. Nine flavonoids displaying cholinesterase inhibitory activity were isolated from the root bark of Morus lhou L., a cultivated edible plant. The isolated compounds were identified as a new flavone (1), 5′-geranyl-5,7, 2′,4′-tetrahydroxyflavone (2), kuwanon U (3), kuwanon E (4), morusin (5), morusinol (6), cyclomorusin (7), neocyclomorusin (8), and kuwanon C (9). All compounds apart from compound 6 inhibited cholinesterase enzyme in a dose-dependent manner with Ki values ranging between 3.1 and 37.5 μMand between 1.7 and 19.1 μM against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, respectively. The new compound was charactierized as 5′-geranyl-4′-methoxy-5,7,2′- trihydroxyflavone (1). It showed the most potent inhibitory activity (Ki = 3.1 μM for AChE, Ki = 1.74 μMfor BChE). Lineweaver-Burk and Dixon plots and their secondary replots indicated that flavones (5-9) with prenyl substitution on C-3 were noncompetitive inhibitors, whereas those unsubstituted (1-4) at C-3 were mixed inhibitors of both AChE and BChE. In conclusion, this is the first study to demonstrate that alkylated flavonoids of M. lhou have potent inhibitory activities against AChE and BChE.