title: Anti-amyloidogenic effects of ID1201, the ethanolic extract of the fruits of Melia toosendan, through activation of the phosphatidylinositol 3-kinase/Akt pathway.
abstract: Amyloid beta (Aβ) peptides, which are generated from amyloid precursor protein (APP), are thought to play a major role in the pathogenesis of Alzheimer's disease (AD). This study investigated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using human embryonic kidney 293 cells with stably expressed human wild-type or Swedish mutant APP695 and β-secretase 1. ID1201 treatment enhanced the non-amyloidogenic metabolism of APP; increases in soluble APPα levels and decreases in soluble APPβ and Aβ levels resulted from the α-secretase activation through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, ID1201-treated 5×familial AD (FAD) mice with 5 mutations in APP and presenilin 1 showed reduced levels of Aβ and amyloid plaques in the brain relative to those of 5×FAD mice with vehicle treatments. These results indicate that ID1201 possesses anti-amyloidogenic effects via the activation of the PI3K/Akt pathway, suggesting that it is a potential therapeutic agent for AD.
authors.affiliation: ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea.
authors.forename: Hanbyeol
authors.initials: H
authors.lastname: Park
authors.affiliation: ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea.
authors.forename: Jong-Su
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea. Electronic address: swyeon@ildong.com.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Yeon
authors.affiliation: ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D000431:Ethanol / Q000737:chemistry; D005638:Fruit; D006801:Humans; D031585:Melia; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D053764:Presenilin-1 / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D012997:Solvents / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D053764:Presenilin-1; D012997:Solvents; C580804:presenilin 1, mouse; D000431:Ethanol; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer's disease; Amyloid beta; Anti-amyloidogenic; ID1201; Meliae Fructus