{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:15:47Z","timestamp":1788477347495,"version":"build-2803163510"},"reference-count":60,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T00:00:00Z","timestamp":1554336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B4005845"],"award-info":[{"award-number":["2017R1A2B4005845"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cholinesterase, \u03b2-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) are the three main enzymes responsible for the early onset of Alzheimer\u2019s disease (AD). The main aim of the present study was to delineate and accentuate the triple-inhibitory potential of arylbenzofurans from Morus alba against these enzymes. Overall, the enzyme inhibition assays demonstrated the prominence of mulberrofuran D2 as an inhibitor of AChE, BChE, BACE1, and GSK-3\u03b2 enzymes with IC50 values of 4.61, 1.51, 0.73, and 6.36 \u03bcM, respectively. Enzyme kinetics revealed different modes of inhibition, and in silico modeling suggested that mulberrofuran D2 inhibited these enzymes with low binding energy through hydrophilic, hydrophobic, and \u03c0\u2013cation interactions in the active site cavities. Similarly, in A\u03b2-aggregation assays, mulberrofuran D2 inhibited self-induced and AChE-induced A\u03b2 aggregation in a concentration-dependent manner that was superior to reference drugs. These results suggest that arylbenzofurans from M. alba, especially mulberrofuran D2, are triple inhibitors of cholinesterase, BACE1, and GSK-3\u03b2 and may represent a novel class of anti-AD drugs.<\/jats:p>","DOI":"10.1021\/acsomega.9b00198","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T11:17:17Z","timestamp":1554376637000},"page":"6283-6294","source":"Crossref","is-referenced-by-count":32,"title":["Arylbenzofurans from the Root Bark of\n                    <i>Morus alba<\/i>\n                    as Triple Inhibitors of Cholinesterase,\n\u03b2-Site Amyloid Precursor Protein Cleaving Enzyme 1, and\nGlycogen Synthase Kinase-3\u03b2: Relevance to Alzheimer\u2019s\nDisease"],"prefix":"10.1021","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8482-1129","authenticated-orcid":true,"given":"Pradeep","family":"Paudel","sequence":"first","affiliation":[{"name":"Pukyong National University , , ,","place":["Busan, Republic of Korea, 48513"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Hui","family":"Seong","sequence":"additional","affiliation":[{"name":"Pukyong National University , , ,","place":["Busan, Republic of Korea, 48513"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pukyong National University , , ,","place":["Busan, Republic of Korea, 48513"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manh Tuan","family":"Ha","sequence":"additional","affiliation":[{"name":"Catholic University of Daegu , , ,","place":["Gyeongbuk, Republic of Korea, 38430"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Sun","family":"Min","sequence":"additional","affiliation":[{"name":"Catholic University of Daegu , , ,","place":["Gyeongbuk, Republic of Korea, 38430"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ah","family":"Jung","sequence":"additional","affiliation":[{"name":"Chonbuk National University , , ,","place":["Jeonju, Republic of Korea, 54896"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-8868","authenticated-orcid":true,"given":"Jae Sue","family":"Choi","sequence":"additional","affiliation":[{"name":"Pukyong National University , , ,","place":["Busan, Republic of Korea, 48513"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"2026090318125667500_cit1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/s0165-0173(97)00016-7","article-title":"Cholinergic activity and amyloid precursor protein\nmetabolism","volume":"25","author":"Roberson","year":"1997","journal-title":"Brain Res. 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