Research Article Phytochemical Analysis and Evaluation of Biological Activity of Lawsonia inermis Seeds Related to Alzheimer’s Disease Majid Balaei-Kahnamoei , 1 Mina Saeedi , 2,3 Arezoo Rastegari , 3 Mohammad Reza Shams Ardekani , 1,3 Tahmineh Akbarzadeh , 4 and Mahnaz Khanavi 1,3,5 1 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 2 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 3 Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran 4 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 5 Faculty of Land and Food Systems, University of British Columbia, Vancouver, British Columbia, Canada Correspondence should be addressed to Mahnaz Khanavi; khanavim@tums.ac.ir Received 7 May 2021; Revised 12 June 2021; Accepted 1 July 2021; Published 19 July 2021 Academic Editor: Wen yi Kang Copyright © 2021 Majid Balaei-Kahnamoei et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Using Lawsonia inermis L. (henna) seeds has been frequently recommended for the improvement of memory in Iranian Traditional Medicine (ITM). In this respect, different fractions of the plant were prepared and evaluated for their in vitro biological assays related to Alzheimer’s disease (AD), including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity as well as metal chelating ability and DPPH antioxidant activity. e dichloromethane and ethyl acetate fractions were able to inhibit the BChE selectively with IC 50 values of 113.47 and 124.90 μg/mL, respectively, compared with donepezil as the reference drug (IC 50 = 1.52 μg/mL). However, all fractions were inactive toward AChE. Phytochemical analysis of the dichloromethane fraction indicated the presence of β-sitosterol ( 1), 3-O-β-acetyloleanolic acid (2), 3-O-(Z)-coumaroyl oleanolic acid (3), betulinic acid (4), and oleanolic acid (5). e inhibitory activity of isolated compounds was also evaluated toward AChE and BChE. Among them, compounds 2 and 5 showed potent inhibitory activity toward BChE with IC 50 values of 77.13 and 72.20 μM, respectively. However, all compounds were inactive toward AChE. Moreover, molecular docking study confirmed desired interactions between those compounds and the BChE active site. e ability of fractions and compounds to chelate biometals (Cu 2+ , Fe 2+ , and Zn 2+ ) was also investigated. Finally, DPPH antioxidant assay revealed that the ethyl acetate (IC 50 = 3.08 μg/mL) and methanol (IC 50 = 3.64 μg/mL) fractions possessed excellent antioxidant activity in comparison to BHA as the positive control (IC 50 = 3.79 μg/mL). 1. Introduction Alzheimer’s disease (AD) is characterized as the most common neurodegenerative disease leading to a gradual decrease in memory, cognitive disorders, psychological and behavioral disturbances, and serious problems in daily ac- tivities. Also, it accounts for more than 70% of dementia cases in elderly people worldwide [1]. e number of pa- tients with AD is predicted to be triple in 2050 [2]. Not only the increasing number of patients with AD in both devel- oped and developing countries, but also the economic burden of disease has encouraged the researchers to develop efficient anti-AD drugs [3]. AD is the consequence of multiple etiological factors including genetics, environment, and lifestyle [4]. e exact origin of AD is not clear and different factors in- cluding reduced levels of acetylcholine (ACh) in the brain [5], intracellular hyperphosphorylation of tau protein and formation of neurofibrillary tangles (NFTs) [6], accelerated aggregation of β-amyloid peptides [7], dys- homeostasis and miscompartmentalization of the bio- metal ions (Fe 2+ , Cu 2+ , and Zn 2+ ) [8], calcium overload Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 5965061, 10 pages https://doi.org/10.1155/2021/5965061