{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T02:03:31Z","timestamp":1789351411052,"version":"build-2803163510"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":77,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015747","name":"University Grants Commission of Bangladesh","doi-asserted-by":"publisher","award":["37-01-0000-073-04-012\/2019"],"award-info":[{"award-number":["37-01-0000-073-04-012\/2019"]}],"id":[{"id":"10.13039\/100015747","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      A recent report showed that\n                      <jats:italic>Stephania japonica<\/jats:italic>\n                      chloroform fraction has potential anticholinesterase and antioxidant activities and is able to improve learning and memory in mice. Therefore, the aim of the present study was to isolate and identify compounds from the chloroform fraction with cholinesterase inhibitory and antioxidant activity that may be useful as new candidates for the treatment of AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Chromatographic methods were used for isolation of compounds and the isolated compounds were analyzed by spectroscopic methods for structure elucidation. Acetyl- and butyryl-cholinesterase inhibitory activity were evaluated for by Ellman\u2019s method and the antioxidant activity by several in vitro models such as DPPH and hydroxyl radicals scavenging, reducing power, total antioxidant activity, and inhibition of brain lipid peroxidation. The interaction of cholinesterase enzymes and isolated compounds were examined by molecular docking studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bioactivity guided approach led to the isolation of four compounds from the chloroform fraction and identified as aknadinine, aknadilactam, aknadicine and stephisoferuline on the basis of their\n                      <jats:sup>1<\/jats:sup>\n                      H-NMR and\n                      <jats:sup>13<\/jats:sup>\n                      C-NMR spectral data. All the compounds were of hasubanan type. They showed significant inhibition against acetylcholinesterase and butyrylcholinesterase, with at least two fold increased affinity for butyrylcholinesterase than acetylcholinesterase. The IC\n                      <jats:sub>50<\/jats:sub>\n                      values of the alkaloids were in the range of 9.36\u201314.89\u00a0\u00b5g\/mL against acetylcholinesterase and 3.97\u20136.66\u00a0\u00b5g\/mL against butyrylcholinesterase. Kinetic analysis revealed that all the four compounds exhibited mixed type of inhibition against both acetylcholinesterase and butyrylcholinesterase. The interaction of compounds with several amino acids of enzymes was supported by molecular docking studies. All the hasubanan alkaloids showed antioxidant activity in all in vitro assays and inhibited peroxidation of brain lipid. The IC\n                      <jats:sub>50<\/jats:sub>\n                      values of the compounds for scavenging of DPPH and hydroxyl radicals, and lipid peroxidation inhibition were found to be in the range of 5.1-40.91, 10.44\u201319.41, and 20.60\u201331.72\u00a0\u00b5g\/mL, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The hasubabanan alkaloids isolated from\n                      <jats:italic>S. japonica<\/jats:italic>\n                      may represent a new class of anti-cholinesterase compounds. The multitargeted activity of hasubanan alkaloids may lead to new candidates for the treatment of AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12906-026-05447-7","type":"journal-article","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T23:04:52Z","timestamp":1782687892000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isolation and identification of hasubanan alkaloids having anti-cholinesterase and antioxidant activity from the stem Stephania japonica"],"prefix":"10.1186","volume":"26","author":[{"given":"Anik Kumar","family":"Dey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Yusuf","family":"Al-Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafia","family":"Ferdous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H. M. Khurshid","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz Abdur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Bayazid","family":"Hossen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Nurul Haque","family":"Mollah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Golam","family":"Sadik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"5447_CR1","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/S0140-6736(76)91936-X","volume":"308","author":"P Davies","year":"1976","unstructured":"Davies P, Maloney AJF. Selective loss of central cholinergic neurons in Alzheimer\u2019s disease. Lancet. 1976;308:1403.","journal-title":"Lancet"},{"key":"5447_CR2","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.3390\/pharmaceutics15041133","volume":"15","author":"H Chen","year":"2023","unstructured":"Chen H, Xu J, Xu H, Luo T, Li Y, Jiang K, Shentu Y, Tong Z. New insights into Alzheimer\u2019s disease: novel pathogenesis, drug target and delivery. Pharmaceutics. 2023;15:1133. https:\/\/doi.org\/10.3390\/pharmaceutics15041133.","journal-title":"Pharmaceutics"},{"key":"5447_CR3","doi-asserted-by":"crossref","unstructured":"Greig N.H., Utsuki T., Ingram D.K., Wang Y., Pepeu G., Scali C., Yu Q-S., Mamczarz J., Holloway H.W., Giordano T., Chen D., Furukawa K., Sambamurti K., Brossi A., Lahiri D.K. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proc Natl Acad Sci. 2005;102:17213\u20138.","DOI":"10.1073\/pnas.0508575102"},{"key":"5447_CR4","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1093\/brain\/awy132","volume":"141","author":"H Hampel","year":"2018","unstructured":"Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, Khachaturian AS, Vergallo A, Cavedo E, Snyder PJ, Khachaturian ZS. The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease. Brain. 2018;141:1917\u201333. https:\/\/doi.org\/10.1093\/brain\/awy132.","journal-title":"Brain"},{"key":"5447_CR5","doi-asserted-by":"publisher","unstructured":"Pang R, Jia Q, Ma C, Li T, Bi W, Wang H, Liu R, Chen P, Lee ES, Jiang HB. Alzheimer\u2019s disease: the current and emerging treatment approaches. Behav Neurol. 2025;2025(9627699). https:\/\/doi.org\/10.1155\/bn\/9627699.","DOI":"10.1155\/bn\/9627699"},{"key":"5447_CR6","doi-asserted-by":"publisher","first-page":"101619","DOI":"10.1016\/j.arr.2022.101619","volume":"77","author":"R Bai","year":"2022","unstructured":"Bai R, Guo J, Ye XY, Xie Y, Xie T. Oxidative stress: The core pathogenesis and mechanism of Alzheimer\u2019s disease. Age Res Rev. 2022;77:101619. https:\/\/doi.org\/10.1016\/j.arr.2022.101619.","journal-title":"Age Res Rev"},{"key":"5447_CR7","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1152\/physrev.00030.2022","volume":"104","author":"M Perluigi","year":"2024","unstructured":"Perluigi M, Di F, Domenico, Butterfield DA. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease. Physiol Rev. 2024;104:103\u201397. https:\/\/doi.org\/10.1152\/physrev.00030.2022.","journal-title":"Physiol Rev"},{"issue":"14","key":"5447_CR8","doi-asserted-by":"publisher","first-page":"6980","DOI":"10.3390\/ijms26146980","volume":"26","author":"N Scarano","year":"2025","unstructured":"Scarano N, Musumeci F, Casini B, Brullo C, D\u2019Ursi P, Fossa P, Schenone S, Cichero E. Alzheimer\u2019s disease etiology hypotheses and therapeutic strategies: a perspective. Int J Mol Sci. 2025;26(14):6980. https:\/\/doi.org\/10.3390\/ijms26146980.","journal-title":"Int J Mol Sci"},{"key":"5447_CR9","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.3390\/ijms21041505","volume":"21","author":"YC Kao","year":"2020","unstructured":"Kao YC, Ho PC, Tu YK, Jou IM, Tsai KJ. Lipids and Alzheimer\u2019s disease. Int J Mol Sci. 2020;21:1505. https:\/\/doi.org\/10.3390\/ijms21041505.","journal-title":"Int J Mol Sci"},{"key":"5447_CR10","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.3390\/antiox10081231","volume":"10","author":"C Sharma","year":"2021","unstructured":"Sharma C, Kim SR. Linking oxidative stress and proteinopathy in Alzheimer\u2019s disease. Antioxidants. 2021;10:1231. https:\/\/doi.org\/10.3390\/antiox10081231.","journal-title":"Antioxidants"},{"key":"5447_CR11","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.ejmech.2018.07.033","volume":"156","author":"D Knez","year":"2018","unstructured":"Knez D, Coquelle N, Pi\u0161lar A, \u017dakelj S, Juki\u010d M, Sova M, Mravljak J, Nachon F, Brazzolotto X, Kos J, Colletier JP. Multi-target-directed ligands for treating Alzheimer\u2019s disease: butyrylcholinesterase inhibitors displaying antioxidant and neuroprotective activities. Eur J Med Chem. 2018;156:598\u2013617. https:\/\/doi.org\/10.1016\/j.ejmech.2018.07.033.","journal-title":"Eur J Med Chem"},{"key":"5447_CR12","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","volume":"20","author":"AG Atanasov","year":"2021","unstructured":"Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021;20:200\u201316.","journal-title":"Nat Rev Drug Discov"},{"key":"5447_CR13","doi-asserted-by":"publisher","first-page":"999","DOI":"10.3390\/life13040999","volume":"13","author":"B Koul","year":"2023","unstructured":"Koul B, Farooq U, Yadav D, Song M. Phytochemicals: a promising alternative for the prevention of Alzheimer\u2019s disease. Life. 2023;13:999. https:\/\/doi.org\/10.3390\/life13040999.","journal-title":"Life"},{"key":"5447_CR14","doi-asserted-by":"publisher","first-page":"728","DOI":"10.3390\/molecules26030728","volume":"26","author":"YR Kong","year":"2021","unstructured":"Kong YR, Tay KC, Su YX, Wong CK, Tan WN, Khaw KY. Potential of naturally derived alkaloids as multi-targeted therapeutic agents for neurodegenerative diseases. Molecules. 2021;26:728. https:\/\/doi.org\/10.3390\/molecules26030728.","journal-title":"Molecules"},{"key":"5447_CR15","unstructured":"Ghani A. Medicinal plants of Bangladesh. Dhaka Asiat Soc Bangladesh. 2003;321."},{"key":"5447_CR16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1080\/10496475.2020.1786874","volume":"27","author":"S Rudra","year":"2021","unstructured":"Rudra S, Islam KN, Rahman MM, Uddin SB. Medicinal plant diversity and their therapeutic uses in selected village common forests in chittagong hill tracts, Bangladesh. J Herbs Spices Med Plants. 2021;27:83\u2013107. https:\/\/doi.org\/10.1080\/10496475.2020.1786874.","journal-title":"J Herbs Spices Med Plants"},{"key":"5447_CR17","first-page":"154","volume":"2","author":"M Hossain","year":"2017","unstructured":"Hossain M, Azad MAK, Tareq SM, Islam MT. Botanical and phyto-pharmacological reports on Stephania japonica. Int J Appl Pharm Sci Res. 2017;2:154\u201360.","journal-title":"Int J Appl Pharm Sci Res"},{"key":"5447_CR18","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1080\/10942912.2015.1048355","volume":"19","author":"MN Uddin","year":"2016","unstructured":"Uddin MN, Ahmed NU, Rahman MA, Akter R, Akter R. Antioxidative potential of the polyphenolics of Stephania japonica var. Discolor (Blume) Forman: a chromatographic (high-performance liquid chromatography) and spectrophotometric measure. Int J Food Prop. 2016;19:911\u201328.","journal-title":"Int J Food Prop"},{"key":"5447_CR19","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8305271","author":"MY Al-Amin","year":"2022","unstructured":"Al-Amin MY, Lahiry A, Ferdous R, Hasan KK, Kader MA, Alam AHM, Saud ZA, Sadik MG. Stephania japonica ameliorates scopolamine-induced memory impairment in mice through inhibition of acetylcholinesterase and oxidative stress. Adv Pharmacol Pharma Sci. 2022. . Article ID 8305271. https:\/\/doi.org\/10.1155\/2022\/8305271. Article ID 8305271.","journal-title":"Adv Pharmacol Pharma Sci"},{"key":"5447_CR20","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1351\/pac197021020227","volume":"21","author":"MS Kupchan","year":"1970","unstructured":"Kupchan MS. Recent advances in the chemistry of terpenoid tumor inhibitors. Pure Appl Chem. 1970;21:227\u201346. https:\/\/doi.org\/10.1351\/pac197021020227.","journal-title":"Pure Appl Chem"},{"key":"5447_CR21","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1021\/np960080d","volume":"59","author":"N Kashiwaba","year":"1996","unstructured":"Kashiwaba N, Morooka S, Kimura M, Ono M, Toda J, Suzuki H, Sano T. New morphinane and hasubanane alkaloids from Stephania cepharantha. J Nat Prod. 1996;59:476\u201380. https:\/\/doi.org\/10.1021\/np960080d.","journal-title":"J Nat Prod"},{"key":"5447_CR22","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1021\/np0500833","volume":"68","author":"H Zhang","year":"2005","unstructured":"Zhang H, Yue JM. Hasubanan type Alkaloids from Stephania longa. J Nat Prod. 2005;68:1201\u20137. https:\/\/doi.org\/10.1021\/np0500833.","journal-title":"J Nat Prod"},{"key":"5447_CR23","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/S0040-4020(01)97839-1","volume":"26","author":"BK Moza","year":"1970","unstructured":"Moza BK, Bhaburi B, Basu DK, Kunitomo J, Okamoto Y, Yuge E, Nagai Y, Ibuka T. Constitution of three new alkaloids, aknadinine (4-demethylhasubanonine), aknadicine (4-demethylnorhasubanonine), and aknadilactam (4-demethyl-16-oxohasubanonine). Tetrahedron. 1970;26:427\u201333. https:\/\/doi.org\/10.1016\/S0040-4020(01)97839-1.","journal-title":"Tetrahedron"},{"key":"5447_CR24","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1021\/np100009j","volume":"73","author":"AR Carroll","year":"2010","unstructured":"Carroll AR, Arumugan T, Redburn J, Ngo A, Guymer GP, Forster PI, Quinn RJ. Hasubanan alkaloids with \u03b4-opioid binding affinity from the aerial parts of Stephania japonica. J Nat Prod. 2010;73:988\u201391. https:\/\/doi.org\/10.1021\/np100009j.","journal-title":"J Nat Prod"},{"key":"5447_CR25","doi-asserted-by":"publisher","first-page":"4975","DOI":"10.1016\/S0040-4039(00)89324-7","volume":"11","author":"SM Kupchan","year":"1970","unstructured":"Kupchan SM, Suffness MI. The structure of stephisoferuline, a new hasubanan ester alkaloid from Stephania hernandifolia. Tetrahedron Lett. 1970;11:4975\u20138. https:\/\/doi.org\/10.1016\/S0040-4039(00)89324-7.","journal-title":"Tetrahedron Lett"},{"key":"5447_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12906-021-03373-4","volume":"21","author":"MA Islam","year":"2021","unstructured":"Islam MA, Zaman S, Biswas K, Al-Amin MY, Hasan MK, Alam AHMK, Tanaka T, Sadik G. Evaluation of cholinesterase inhibitory and antioxidant activity of Wedelia chinensis and isolation of apigenin as an active compound. BMC Complement Med Ther. 2021;21:1\u201312. https:\/\/doi.org\/10.1186\/s12906-021-03373-4.","journal-title":"BMC Complement Med Ther"},{"key":"5447_CR27","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265\u201375.","journal-title":"J Biol Chem"},{"key":"5447_CR28","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","volume":"7","author":"GL Ellman","year":"1961","unstructured":"Ellman GL, Courtney KD, Andres JV, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88\u201395. https:\/\/doi.org\/10.1016\/0006-2952(61)90145-9.","journal-title":"Biochem Pharmacol"},{"key":"5447_CR29","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5569054","author":"S Ahammed","year":"2021","unstructured":"Ahammed S, Afrin R, Uddin N, Al-Amin MY, Hasan K, Haque U, Islam KM, Alam AHMK, Tanaka T, Sadik G. Acetylcholinesterase inhibitory and antioxidant activity of the compounds isolated from Vanda roxburghii. Adv Pharmacol Pharma Sci 2021. https:\/\/doi.org\/10.1155\/2021\/5569054. Article ID 5569054.","journal-title":"Adv Pharmacol Pharma Sci"},{"key":"5447_CR30","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0076-6879(94)33008-5","volume":"233","author":"OI Aruoma","year":"1994","unstructured":"Aruoma OI. Deoxyribose assay for detecting hydroxyl radicals. Methods Enzymol. 1994;233:57\u201366. https:\/\/doi.org\/10.1016\/S0076-6879(94)33008-5. Academic Press.","journal-title":"Methods Enzymol"},{"key":"5447_CR31","doi-asserted-by":"publisher","first-page":"307","DOI":"10.5264\/eiyogakuzashi.44.307","volume":"44","author":"M Oyaizu","year":"1986","unstructured":"Oyaizu M. Studies on products of browning reaction antioxidative activities of products of browning reaction prepared from glucosamine. Jpn J Nutr Diet. 1986;44:307\u201315.","journal-title":"Jpn J Nutr Diet"},{"key":"5447_CR32","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1006\/abio.1999.4019","volume":"269","author":"P Prieto","year":"1999","unstructured":"Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal Biochem. 1999;269:337\u201341. https:\/\/doi.org\/10.1006\/abio.1999.4019.","journal-title":"Anal Biochem"},{"key":"5447_CR33","doi-asserted-by":"publisher","first-page":"117095","DOI":"10.1016\/j.jep.2023.117095","volume":"319","author":"R Ferdous","year":"2024","unstructured":"Ferdous R, Islam MB, Al-Amin MY, Dey AK, Mondal MOA, Islam MN, Alam AK, Rahman AA, Sadik MG. Anticholinesterase and antioxidant activity of Drynaria quercifolia and its ameliorative effect in scopolamine-induced memory impairment in mice. J Ethnopharmacol. 2024;319:117095. https:\/\/doi.org\/10.1016\/j.jep.2023.117095.","journal-title":"J Ethnopharmacol"},{"key":"5447_CR34","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8862025","author":"SS Lopa","year":"2021","unstructured":"Lopa SS, Al-Amin MY, Hasan MK, Ahammed MS, Islam KM, Alam AHM, Tanaka T, Sadik MG. Phytochemical analysis and cholinesterase inhibitory and antioxidant activities of Enhydra fluctuans relevant in the management of Alzheimer\u2019s disease. Int J Food Sci. 2021. https:\/\/doi.org\/10.1155\/2021\/8862025.","journal-title":"Int J Food Sci"},{"key":"5447_CR35","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1107\/S0907444902003451","volume":"58","author":"HM Berman","year":"2002","unstructured":"Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, Feng Z, Gilliland GL, Iype L, Jain S, Fagan P. The protein data bank. Acta Crystallogr Sect D: Biol Crystallogr. 2002;58:899\u2013907. https:\/\/doi.org\/10.1107\/S0907444902003451.","journal-title":"Acta Crystallogr Sect D: Biol Crystallogr"},{"key":"5447_CR36","doi-asserted-by":"crossref","unstructured":"Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Chem Bio 2015, 243\u201350.","DOI":"10.1007\/978-1-4939-2269-7_19"},{"key":"5447_CR37","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009;30:2785\u201391. https:\/\/doi.org\/10.1002\/jcc.21256.","journal-title":"J Comput Chem"},{"key":"5447_CR38","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455\u201361. https:\/\/doi.org\/10.1002\/jcc.21334.","journal-title":"J Comput Chem"},{"key":"5447_CR39","first-page":"51","volume":"993","author":"E Krieger","year":"2013","unstructured":"Krieger E, Vriend G, Spronk C. YASARA\u2013yet another scientific artificial reality application. YASARA org. 2013;993:51\u201378.","journal-title":"YASARA org"},{"key":"5447_CR40","doi-asserted-by":"publisher","unstructured":"Alzheimer\u2019s Association Report. 2023 Alzheimer\u2019s disease facts and figures. Alzheimers Dement. 2023;19:1598\u20131695. https:\/\/doi.org\/10.1002\/alz.13016.","DOI":"10.1002\/alz.13016"},{"key":"5447_CR41","doi-asserted-by":"publisher","unstructured":"Alzheimer\u2019s Association Report. 2022 Alzheimer\u2019s disease facts and figures. Alzheimers Dement. 2022;18:700\u2013789. https:\/\/doi.org\/10.1002\/alz.12638.","DOI":"10.1002\/alz.12638"},{"key":"5447_CR42","doi-asserted-by":"publisher","unstructured":"Singh AK, Rai SN, Maurya A, Mishra G, Awasthi R, Shakya A, Chellappan DK, Dua K, Vamanu E, Chaudhary SK, Singh MP. Therapeutic potential of phytoconstituents in management of Alzheimer\u2019s disease. Evid Based Complement Altern Med. 2021;1\u201319. https:\/\/doi.org\/10.1155\/2021\/5578574.","DOI":"10.1155\/2021\/5578574"},{"key":"5447_CR43","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1080\/14786419.2018.1539979","volume":"34","author":"G Zeng","year":"2020","unstructured":"Zeng G, Wu Z, Cao W, Wang Y, Deng X, Zhou Y. Identification of anti-nociceptive constituents from the pollen of Typha angustifolia L. using effect-directed fractionation. Nat Prod Res. 2020;34:1041\u20135. https:\/\/doi.org\/10.1080\/14786419.2018.1539979.","journal-title":"Nat Prod Res"},{"key":"5447_CR44","doi-asserted-by":"publisher","first-page":"e202300721","DOI":"10.1002\/cmdc.202300721","volume":"19","author":"Y Wang","year":"2024","unstructured":"Wang Y, Sun F, Liang Y, Zhou D, Chen G, Li N, Distribution N. Structures, Synthesis, and Bioactivity of Hasubanan Alkaloids. ChemMedChem. 2024;19:e202300721. https:\/\/doi.org\/10.1002\/cmdc.202300721.","journal-title":"ChemMedChem"},{"key":"5447_CR45","doi-asserted-by":"publisher","first-page":"552453","DOI":"10.3389\/fphar.2020.552453","volume":"11","author":"CK Kong","year":"2021","unstructured":"Kong CK, Low LE, Siew WS, Yap WH, Khaw KY, Ming LC, Mocan A, Goh BH, Goh PH. Biological activities of snowdrop (Galanthus spp., Family Amaryllidaceae). Front Pharmacol. 2021;11:552453. https:\/\/doi.org\/10.3389\/fphar.2020.552453.","journal-title":"Front Pharmacol"},{"key":"5447_CR46","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1002\/ddr.21726","volume":"81","author":"Q-Q Lu","year":"2020","unstructured":"Lu Q-Q, Chen Y-M, Liu H-R, Yan J-Y, Cui P-W, Zhang Q-F, Gao X-H, Feng X, Liu Y-Z. Nitrogen-containing flavonoid and their analogs with diverse B-ring in acetylcholinesterase and butyrylcholinesterase inhibition. Drug Dev Res. 2020;81:1037\u201347. https:\/\/doi.org\/10.1002\/ddr.21726.","journal-title":"Drug Dev Res"},{"key":"5447_CR47","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.3390\/molecules25194545","volume":"25","author":"NAN Azman","year":"2020","unstructured":"Azman NAN, Alhawarri MB, Rawa MSA, Dianita R, Gazzali AM, Nogawa T, Wahab HA. Potential anti-acetylcholinesterase activity of Cassia timorensis DC. Molecules. 2020;25:4545.","journal-title":"Molecules"},{"key":"5447_CR48","doi-asserted-by":"publisher","first-page":"e70297","DOI":"10.1002\/pro.70297","volume":"34","author":"LW Hung","year":"2025","unstructured":"Hung LW, Sanbonmatsu KY, Williams RF, Chen JC. Acetylcholinesterase: structure, dynamics, and interactions with organophosphorus compounds. Protein Sci. 2025;34:e70297. . PMID: 40970461; PMCID: PMC12447245. https:\/\/doi.org\/10.1002\/pro.70297. PMID: 40970461; PMCID: PMC12447245.","journal-title":"Protein Sci"},{"key":"5447_CR49","doi-asserted-by":"publisher","first-page":"7529","DOI":"10.1021\/bi052176p","volume":"45","author":"D Su\u00e1rez","year":"2006","unstructured":"Su\u00e1rez D, D\u00edaz N, Fontecilla-Camps J, Field MJ. A computational study of the deacylation mechanism of human butyrylcholinesterase. Biochemistry. 2006;45:7529\u201343. https:\/\/doi.org\/10.1021\/bi052176p.","journal-title":"Biochemistry"},{"key":"5447_CR50","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s13065-024-01170-x","volume":"18","author":"A Asadipour","year":"2024","unstructured":"Asadipour A, Pourshojaei Y, Mansouri M. Amino-7,8-dihydro-4H-chromenone derivatives as potential inhibitors of acetylcholinesterase and butyrylcholinesterase for Alzheimer\u2019s disease management; in vitro and in silico study. BMC Chem. 2024;18:70. https:\/\/doi.org\/10.1186\/s13065-024-01170-x.","journal-title":"BMC Chem"},{"key":"5447_CR51","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/8056462","author":"M Hatami","year":"2023","unstructured":"Hatami M, Mortazavi M, Baseri Z, Khani B, Rahimi M, Babaei S. Antioxidant compounds in the treatment of Alzheimer\u2019s Disease: natural, hybrid, and synthetic products. Evid Based Complement Altern Med. 2023. https:\/\/doi.org\/10.1155\/2023\/8056462.","journal-title":"Evid Based Complement Altern Med"},{"key":"5447_CR52","doi-asserted-by":"publisher","first-page":"554","DOI":"10.3390\/antiox11030554","volume":"11","author":"SNA Bukhari","year":"2022","unstructured":"Bukhari SNA. Dietary polyphenols as therapeutic intervention for Alzheimer\u2019s disease: a mechanistic insight. Antioxidants. 2022;11:554.","journal-title":"Antioxidants"},{"key":"5447_CR53","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1111\/jphp.12090","volume":"65","author":"EL Konrath","year":"2013","unstructured":"Konrath EL, Passos CDS, Klein-J\u00fanior LC, Henriques AT. Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer\u2019s disease. J Pharm Pharmacol. 2013;65:1701\u201325. https:\/\/doi.org\/10.1111\/jphp.12090.","journal-title":"J Pharm Pharmacol"},{"key":"5447_CR54","doi-asserted-by":"publisher","unstructured":"King SM, Herzon SB. The hasubanan and acutumine alkaloids. In The Alkaloids: Chemistry and Biology. 2014;73:161\u2013222. Academic Press. https:\/\/doi.org\/10.1016\/B978-0-12-411565-1.00003-2.","DOI":"10.1016\/B978-0-12-411565-1.00003-2"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12906-026-05447-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-026-05447-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-026-05447-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:37:28Z","timestamp":1789349848000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12906-026-05447-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5447"],"URL":"https:\/\/doi.org\/10.1186\/s12906-026-05447-7","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"23 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approval for the experimental protocol was received from the Institute of Biological Sciences, University of Rajshahi, Bangladesh [No: 336(18)\/320\/IAMEBBC\/IBSc].","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"270"}}