{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:21:35Z","timestamp":1793388095424,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ICMR","award":["3\/1\/3\/196\/Neuro\/2021-NCD-I"],"award-info":[{"award-number":["3\/1\/3\/196\/Neuro\/2021-NCD-I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a neurodegenerative disease characterized by beta-amyloid (A\u03b2) deposition and increased acetylcholinesterase (AchE) enzyme activities. Indole 3 carbinol (I3C) and diindolylmethane (DIM) are reported to have neuroprotective activities against various neurological diseases, including ischemic stroke, Parkinson\u2019s disease, neonatal asphyxia, depression, stress, neuroinflammation, and excitotoxicity, except for AD. In the present study, we have investigated the anti-AD effects of I3C and DIM. Methods: Docking and molecular dynamic studies against AchE enzyme and network pharmacological studies were conducted for I3C and DIM. I3C and DIM\u2019s neuroprotective effects against self and AchE-induced A\u03b2 aggregation were investigated. The neuroprotective effects of I3C and DIM against A\u03b2-induced neurotoxicity were assessed in SH-S5Y5 cells by observing cell viability and ROS. Results: Docking studies against AchE enzyme with I3C and DIM show binding efficiency of \u22127.0 and \u221210.3, respectively, and molecular dynamics studies revealed a better interaction and stability between I3C and AchE and DIM and AchE. Network pharmacological studies indicated that I3C and DIM interacted with several proteins involved in the pathophysiology of AD. Further, I3C and DIM significantly inhibited the AchE (IC50: I3C (18.98 \u00b5M) and DIM (11.84 \u00b5M)) and self-induced A\u03b2 aggregation. Both compounds enhanced the viability of SH-S5Y5 cells that are exposed to A\u03b2 and reduced ROS. Further, I3C and DIM show equipotential neuroprotection when compared to donepezil. Conclusions: Our findings indicate that both I3C and DIM show anti-AD effects by inhibiting the A\u03b2 induced neurotoxicity and AchE activities.<\/jats:p>","DOI":"10.3390\/diseases12080184","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T04:29:57Z","timestamp":1723782597000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Indole-3 Carbinol and Diindolylmethane Mitigated \u03b2-Amyloid-Induced Neurotoxicity and Acetylcholinesterase Enzyme Activity: In Silico, In Vitro, and Network Pharmacology Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2067-1410","authenticated-orcid":false,"given":"Kakarla","family":"Ramakrishna","sequence":"first","affiliation":[{"name":"KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur 522302, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praditha","family":"Karuturi","sequence":"additional","affiliation":[{"name":"KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur 522302, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Queen","family":"Siakabinga","sequence":"additional","affiliation":[{"name":"KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur 522302, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajendra","family":"T.A.","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, IIT BHU, Varanasi 221005, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairam","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, IIT BHU, Varanasi 221005, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-9597","authenticated-orcid":false,"given":"Shreya","family":"Singh","sequence":"additional","affiliation":[{"name":"SBS College of Pharmacy, Malwan, Fatehpur 212664, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali 160062, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9762-3500","authenticated-orcid":false,"given":"G. Siva","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali 160062, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Elizabeth","family":"Sobhia","sequence":"additional","affiliation":[{"name":"Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali 160062, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-9549","authenticated-orcid":false,"given":"Sachchida Nand","family":"Rai","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1474-4422(18)30403-4","article-title":"Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Nichols","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, X., Feng, X., Sun, X., Hou, N., Han, F., and Liu, Y. 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