title: Potent inhibition of monoamine oxidase A by decursin from Angelica gigas Nakai and by wogonin from Scutellaria baicalensis Georgi.
abstract: During the ongoing search for new monoamine oxidase (MAO) inhibitors, five coumarin derivatives and eight flavonoids were isolated from the roots of Angelica gigas Nakai and Scutellaria baicalensis Georgi, respectively. Of the phytochemicals, decursin (4) was found to potently and selectively inhibit human MAO-A (IC50=1.89μM). The IC50value of 4 for MAO-A belonged to the lowest group in herbal sources and was similar to that of toloxatone (1.78μM), a marketed drug. Wogonin (11) effectively inhibited MAO-A and MAO-B (IC50=6.35 and 20.8μM, respectively). Furthermore, compounds 5 (decursinol angelate) and 10 (baicalein) were observed to selectively and moderately inhibit MAO-A. In addition, compound 4 reversibly and competitively inhibited MAO-A with a Kiof 0.17μM. Compound 11 also competitively inhibited MAO-A and MAO-B (Ki=0.56 and 1.96μM, respectively). Molecular docking simulation revealed that 4 interacts with Asn181 residue of MAO-A or Asn116 residue of MAO-B by formation of hydrogen bond. The findings suggest compounds 4 and 11 be considered as new potent and reversible MAO-A inhibitors or useful lead compounds for the developments of MAO inhibitors for the treatment of disorders like depression, Parkinson's disease and Alzheimer disease.
authors.affiliation: Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors.forename: Myung-Gyun
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.affiliation: National Development Institute of Korean Medicine, Gyeongsan 38540, Republic of Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Lee
authors.affiliation: National Development Institute of Korean Medicine, Gyeongsan 38540, Republic of Korea.
authors.forename: Heung Mook
authors.initials: HM
authors.lastname: Shin
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea. Electronic address: hoon@sunchon.ac.kr.
authors.forename: Hoon
authors.initials: H
authors.lastname: Kim
mesh_terms: D029969:Angelica / Q000737:chemistry*; D001578:Benzopyrans / Q000378:metabolism / Q000494:pharmacology*; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology*; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D031364:Scutellaria baicalensis / Q000737:chemistry*
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D044950:Flavanones; D008996:Monoamine Oxidase Inhibitors; C101278:decursin; D008995:Monoamine Oxidase; C085514:wogonin
keywords: Decursin; Monoamine oxidase inhibition; Wogonin