{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:27:32Z","timestamp":1785191252462,"version":"3.55.0"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"15","funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"crossref","award":["94-01-33-28734"],"award-info":[{"award-number":["94-01-33-28734"]}],"id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Restoration of cholinergic function is considered a rational approach to enhance cognitive performance. Acetylcholinesterase inhibitors are still the best therapeutic option for Alzheimer\u02bcs disease. The fruits of Piper longum have been used in traditional medicines for the treatment of memory loss. It was demonstrated that the dichloromethane extract of these fruits is able to inhibit acetylcholinesterase. Thus, the aim of this study was to identify the contained acetylcholinesterase inhibitors. The active zones were presented via TLC-bioautography, and five compounds were isolated in the process of a bioassay-guided phytochemical investigation. Their structures were characterized as piperine, methyl piperate, guineenisine, pipercide, and pellitorine using spectroscopy and spectrometry methods (UV, IR, MS, 1H-, and 13C-NMR). In vitro acetylcholinesterase inhibitory activities of the isolates and their IC50 values were\n\t\t\t\t\tdetermined via a colorimetric assay. Three of them exhibited enzyme inhibitory activities, with piperine being the most potent compound (IC50 of 0.3\u2009mM). In order to investigate the binding mode of the tested compounds, docking studies were performed using the X-ray crystal structure of acetylcholinesterase from Tetronarce californica with the Protein Data Bank code 1EVE. The content of the active compounds in the extract was determined by a developed HPLC method. Piperine was present in the maximum quantity in the fruits (0.57%), whereas methyl piperate contained the minimum content (0.10%).<\/jats:p>","DOI":"10.1055\/a-1199-7084","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T22:48:01Z","timestamp":1594853281000},"page":"1118-1124","source":"Crossref","is-referenced-by-count":12,"title":["Isolation and Characterization of Acetylcholinesterase Inhibitors from Piper longum and Binding Mode Predictions"],"prefix":"10.1055","volume":"86","author":[{"given":"Zakie","family":"Khatami","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Herdlinger","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Paracelsus Medical University, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parisa","family":"Sarkhail","sequence":"additional","affiliation":[{"name":"Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zehl","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre & Department of Analytical Chemistry, University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanspeter","family":"Kaehlig","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Schuster","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Paracelsus Medical University, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-047X","authenticated-orcid":false,"given":"Hamid-Reza","family":"Adhami","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cger.2014.04.001","article-title":"Dementia and cognitive impairment: epidemiology, diagnosis, and treatment","volume":"30","author":"J Hugo","year":"2014","journal-title":"Clin Geriatr Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2012.11.006","article-title":"The worldwide economic impact of dementia 2010. 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