Angiotensin-I-Converting Enzyme Inhibitory Activity of Coumarins from Angelica decursiva

The bioactivity of ten traditional Korean Angelica species were screened by angiotensin-converting enzyme (ACE) assay in vitro. Among the crude extracts, the methanol extract of Angelica decursiva whole plants exhibited potent inhibitory effects against ACE. In addition, the ACE inhibitory activity of coumarins 1−5, 8−18 was evaluated, along with two phenolic acids (6, 7) obtained from A. decursiva. Among profound coumarins, 11−18 were determined to manifest marked inhibitory activity against ACE with IC50 values of 4.68−20.04 µM. Compounds 12, 13, and 15 displayed competitive inhibition against ACE. Molecular docking studies confirmed that coumarins inhibited ACE via many hydrogen bond and hydrophobic interactions with catalytic residues and zinc ion of C- and N-domain ACE that blocked the catalytic activity of ACE. The results derived from these computational and in vitro experiments give additional scientific support to the anecdotal use of A. decursiva in traditional medicine to treat cardiovascular diseases such as hypertension.