Angiotensin converting enzyme inhibitory benzopyranoids from Angelica gigas

Angiotensin converting enzyme (ACE) plays a major role in the regulation of blood pressure. The potential antihypertensive activity of Angelica gigas was evaluated in vitro by its ability to inhibit ACE. A methanol extract of A. gigas roots exerted an inhibitory effect against ACE and was fractionated using several organic solvents, including dichloromethane, ethyl acetate, and n -butanol. The n -butanol soluble fraction, which manifested potent ACE inhibitory properties, was further purified via repeated silica gel and RP-18 column chromatography. Three benzopyriansides, such as nodakenin ( 1 ), umbelliferone ( 2 ), and umbelliferone 6-carboxylic acid ( 3 ) were isolated from A. gigas roots. Compounds 1–3 inhibited ACE activity in a dose-dependent manner, with IC 50 values of 63.95±0.16, 190.49±0.54, and 158.35±1.53 μM, respectively. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed that the three compounds showed a mixed-type inhibition. The equilibrium constants for the inhibitor binding (K i ) of 1 , 2 , and 3 were estimated to be 1.56×10 −4 , 4.70×10 −4 , and 2.17×10 −4 M, respectively. We used A. gigas roots to isolate nodakinin, umbelliferone, and umbelliferone 6-carboxylic acid and tested their inhibition efficacy against ACE for the first time.