Phytochemical constituents of Akebiae Caulis and their Aβ42 inhibitory activities.

Abstract

Akebia quinata DECAISENE (Lardizabalaceae) is a creeping woody vine that is widely distributed in East Asia, including Korea, China, and Japan. Traditionally, its dried stem is used mainly as a diuretic agent for the treatment of edema and rheumatic pain. Previous phytochemical investigations resulted in the isolation of triterpenes, triterpene glycosides, phenylethanoid glycosides and megastigmane glycoside. Amyloid β (Aβ), a main component of the senile plaque detected in Alzheimer’s disease, induces cell death. However, a limited number of studies have addressed the biological and pharmacological effects of EtOAc fraction of Akebiae Caulis. In particular, the inhibitory activity against Aβ-42 induced fibrilogenesis of Akebiae Caulis remains unclear. In the present study, by means of repeated column chromatography using silicagel, LiChroprep RP-18, MCI-gel, and MPLC, nine compounds: Pulsatillasaponin A (1), Collinsonidin (2), Akebonic acid (3), Hederagenin (4), 1-(3′, 4′-dihydroxycinnamoyl) cyclopentane-2, 3-diol (5), Asperosaponin C (6), Leontoside A (7), Quinatic acid (8), and Quinatoside A (9) was isolated from the Akebiae Caulis.The chemical structures of compounds (1-9) were identified based on 1D and 2D NMR, including H-H COSY, HSQC, and HMBC spectroscopic analyses. Compound 5 and 6 were isolated from this plant for the first time. For these isolated compounds, the inhibitory activities of Aβ-42 induced fibrilogenesis were examined. Among these isolated compounds, compound 2,3,and 6 have significant inhibitory effects against Aβ-42 induced fibrilogenesis. This is the first report on the Aβ-42 inhibitory effects of the components from Akebiae Caulis.|목통(Akebiae Caulis) 은으름덩굴( Akebia quinata Decaisne.) 또는기타동속식물의줄기로주피를제거하고가로로자른것으로한방에서소염, 이뇨, 통경에사용된다.목통의약리활성으로는이뇨, 항진균, 위액분비억제, 지질저하및산후유즙분비촉진작용등이알려져있다.이전의연구에의하면목통(Akebiae Caulis)으로부터triterpenes, triterpene glycosides, phenylethanoid glycosides, megastigmane glycoside 등을비롯한다양한성분이분리, 보고되었다.본연구실의예비실험결과목통의에틸아세테이트분획이Aβ-42에대한저해뛰어난활성을나타내활성성분의분리를시도하였다. 목통(Akebiae Caulis)의에틸아세테이트분획에대해실리카겔, RP-18, MCI-gel, MPLC 컬럼크로마토그래피를반복적으로수행하여9개의화합물: Pulsatillasaponin A (1), Collinsonidin (2), Akebonic acid (3), Hederagenin (4), 1-(3′, 4′-dihydroxycinnamoyl) cyclopentane-2, 3-diol (5), Asperosaponin C (6), Leontoside A (7), Quinatic acid (8), and Quinatoside A (9) 을분리했다. 화합물들 (1-9)의구조는1H-NMR, 13C-NMR, 1H-1HCOSY, HSQC, HMBC 분광분석등의 1D 및 2D NMR에기초하여확인하였다. 분리된화합물가운데화합물 (5) 및 (6)은목통에서처음으로분리된화합물들이다.분리된화합물에대해, Aβ-42 유도fibrillogenesis의저해활성을조사하였다. 화합물중, 화합물2,3및6은 Aβ-42 유도fibrillogenesis대해상당한억제효과를나타냈다. 본연구에서는목통으로부터분리된화합물들에대해Aβ-42 저해효과여부를처음으로확인하였다.