Acetylcholinesterase Inhibitors Research Articles

Geometry Optimization, Molecular Docking and ADMET Studies of Echimidine Molecule

Plants are an important food group that has been used as a source of nutrition and healing from past to present. Plants contain secondary metabolites that are still under investigation in drug development studies. Alkaloids, which are secondary metabolites, have antioxidant and antibacterial properties as well as therapeutic potential in various diseases such as Alzheimer's disease. Acetylcholinesterase (AChE) inhibitors come to the fore in the treatment strategy of Alzheimer's disease. Echimidine, a pyrrolizidine alkaloid, is an important compound known to be active in AChE inhibition. Molecular docking method has an important place in elucidating biochemical processes by examining the interactions of drugs or drug candidates with the receptors targeted for the disease. Additionally, information on the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of drug candidate molecules is important in drug development studies. In this study, echimidine molecule was optimized, the molecular docking study was carried out with AChE and the interaction types, binding profile, and binding affinity of echimidine was determined. ADMET analysis of echimidine was also realized to estimate its drug potential. With this study, geometry optimization of the molecule, elucidation of its interactions with AChE, and prediction of its pharmacokinetic properties were achieved for the first time.

Essential Oils of Two Subspecies of Satureja montana L. against Gastrointestinal Parasite Anisakis simplex and Acetylcholinesterase Inhibition

The increasing presence of Anisakis spp. in fish is having significant implications for public health due to a rise in cases of anisakiasis. Given this situation, there is a critical need to develop new strategies to fight this parasite. Satureja montana L., commonly known as savory, is a plant recognized in folk medicine for its therapeutic activity, such as being antispasmodic and digestive, among other properties. The aim of this study was to assess the nematicide activity against A. simplex larvae of the essential oil from two varieties of S. montana (subsp. montana (SMM) and variegata (SMV)). The essential oils were obtained via hydro-distillation of the flowering aerial parts. In vitro assays demonstrated the complete inactivation of anisakis larvae after 24 h when exposed to both essential oils, along with a significant reduction in their penetration capacity. Moreover, both essential oils showed an inhibitory effect on acetylcholinesterase (AChE). No differences between the subspecies were observed in any of the assays. Hence, the nematicidal activity of essential oils could be attributed to their capacity to inhibit AChE. These findings suggest the potential of S. montana essential oil for therapeutic and food industry applications.

Determination of Potential Lead Compound from Magnolia officinalis for Alzheimer’s Disease through Pharmacokinetic Prediction, Molecular Docking, Dynamic Simulation, and Experimental Validation

Amyloid β protein (Aβ) deposition has been implicated as the molecular driver of Alzheimer’s disease (AD) progression. The modulation of the formation of abnormal aggregates and their post-translational modification is strongly suggested as the most effective approach to anti-AD. Beta-site APP-cleaving enzyme 1 (BACE1) acts upstream in amyloidogenic processing to generate Aβ, which rapidly aggregates alone or in combination with acetylcholinesterase (AChE) to form fibrils. Accumulated Aβ promotes BACE1 activation via glycogen synthase kinase-3β (GSK-3β) and is post-translationally modified by glutaminyl cyclase (QC), resulting in increased neurotoxicity. A novel multi-target inhibitor as a potential AD agent was identified using an in silico approach and experimental validation. Magnolia officinalis, which showed the best anti-AD activity in our preliminary study, was subjected to analysis, and 82 compounds were studied. Among 23 compounds with drug-likeness, blood–brain barrier penetration, and safety, honokiol emerged as a lead structure for the inhibition of BACE1, AChE, QC, and GSK-3β in docking and molecular dynamics (MD) simulations. Furthermore, honokiol was found to be an excellent multi-target inhibitor of these enzymes with an IC50 of 6–90 μM, even when compared to other natural single-target inhibitors. Taken together, the present study is the first to demonstrate that honokiol acts as a multiple enzyme inhibitor with an excellent pharmacokinetic and safety profile which may provide inhibitory effects in broad-range areas including the overproduction, aggregation, and post-translational modification of Aβ. It also provides insight into novel structural features for the design and discovery of multi-target inhibitors for anti-AD.

Paternal preconception donepezil exposure enhances learning in offspring

BackgroundRecent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring.ResultsIn this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements.ConclusionsThese findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

Molecular interaction mechanisms on (−)-epigallocatechin-3-gallate improving activities of inhibited acetylcholinesterase by selected organophosphorus pesticides in vitro & vivo

(−)-Epigallocatechin-3-gallate (EGCG) is reported to have benefits for the treatment of Alzheimer’s disease by binding with acetylcholinesterase (AChE) to enhance the cholinergic neurotransmission. Organophosphorus pesticides (OPs) inhibited AChE and damaged the nervous system. This study investigated the combined effects of EGCG and OPs on AChE activities in vitro & vivo. The results indicated that EGCG significantly reversed the inhibition of AChE caused by OPs. In vitro, EGCG reactived AChE in three group tubes incubated for 110 min, and in vivo, it increased the relative activities of AChE from less than 20% to over 70% in brain and vertebral of zebrafish during the exposure of 34 h. The study also proposed the molecular interaction mechanisms through the reactive kinetics and computational analyses of density functional theory, molecular docking, and dynamic modeling. These analyses suggested that EGCG occupied the key residues, preventing OPs from binding to the catalytic center of AChE, and interfering with the initial affinity of OPs to the central active site. Hydrogen bonding, conjugation, and steric interactions were identified as playing important roles in the molecular interactions. The work suggests that EGCG antagonized the inhibitions of OPs on AChE activities and potentially offered the neuroprotection against the induced damage.

Alzheimer's Disease and Its a Diagnosis, Symptoms, Pathophysiology, and Treatment

Alzheimer’s disease (AD) is the most prevalent form of dementia, predominantly affecting individuals over 65 years old, though a rare form can manifest in younger people. Globally, AD accounts for approximately 75% of the more than 35 million dementia cases, with projections suggesting the number could rise to 115 million by 2050. The precise etiology of Alzheimer’s remains largely unknown. Historically, dementia has been recognized since ancient times, with significant milestones in understanding and terminology occurring from the 17th century onwards. Alzheimer’s disease is identified by symptoms such as confusion, personality changes, language difficulties, mood swings, and short-term memory disturbance. Pathophysiologically, AD is characterized by amyloid plaques and neurofibrillary tangles (NFTs) which cause brain damage. Diagnosis involves clinical evaluation, neuroimaging, neuropathological findings, and cerebrospinal fluid analysis. Risk factors include genetic predisposition, vascular issues, and psychosocial elements. Current treatments focus on acetylcholinesterase inhibitors to manage symptoms, particularly in the mild to moderate stages of the disease.

The role and mechanism of dapagliflozin in Alzheimer disease: A review.

Alzheimer disease (AD), as the main type of dementia, is primarily characterized by cognitive dysfunction across multiple domains. Current drugs for AD have not achieved the desired clinical efficacy due to potential risks, inapplicability, high costs, significant side effects, and poor patient compliance. However, recent findings offer new hope by suggesting that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) may possess neuroprotective properties, potentially opening up novel avenues for the treatment of AD. This review delves deeply into the multifaceted mechanisms of action of SGLT-2i in AD, encompassing antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, acetylcholinesterase inhibitor activity, and protection of endothelial cells against atherosclerosis and damage to the blood-brain barrier, among others. Furthermore, it provides an overview of recent advances in clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.

In silico study of β-carboline alkaloids as Acetylcholinesterase Inhibitors: Alternative of Natural Products for the Therapeutic Treatment of Alzheimer's Disease

In silico study of β-carboline alkaloids as Acetylcholinesterase Inhibitors: Alternative of Natural Products for the Therapeutic Treatment of Alzheimer's Disease

PyPLIF HIPPOS-aided Construction and Retrospective Validation of Structure-Based Virtual Screening Protocol Targeting VEGFR2

Recently, the discovery of small molecules as inhibitors for vascular endothelial growth factor receptor 2 (VEGFR2) is of timely interest, especially in the area of ocular neovascular diseases. On the other hand, PyPLIF HIPPOS in combination with machine learning techniques has been reported to increase the prediction quality of structure-based virtual screening (SBVS) protocols. The original version of PyPLIF has served in the development of an SBVS protocol that successfully identified novel chalcone derivatives and short peptides as potent inhibitors for acetylcholinesterase. In this short communication, construction and retrospective validation of an SBVS protocol employing PyPLIF HIPPOS targeting VEGFR2 are presented to make it publicly available. The retrospective validation employed 409 active compounds and 24,950 decoys from the enhanced version of the directory of useful decoys. All compounds were docked independently 3 times using AutoDock Vina followed by the identification of the protein-ligand interaction fingerprints (PLIF) employing PyPLIF HIPPOS. The derived ensemble PLIF descriptors were then used in the decision tree construction using a machine-learning technique called recursive partitioning and regression trees. The best decision was then incorporated in the SBVS protocol. The F-measure and enrichment factor values of the SBVS protocol were 0.387 and 76.879, respectively. Hence, the SBVS protocol is readily available to screen small molecules or short peptides.

Synthesis and Acetylcholinesterase Inhibitory Activity of Novel Trilaciclib Analogs.

Trilaciclib is a CDK4/6 inhibitor, used to treat the bone marrow damage in chemotherapy patients. A series of thirteen novel structural trilaciclib analogs was obtained to evaluate their activity against acetylcholinesterase. An effective method for the synthesis of 4,7-substituted 8,9-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives from a new methyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate was developed. Most of the synthesized pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives inhibited acetylcholinesterase in the micromolar range. The obtained data can be used for designing more potent acetylcholinesterase inhibitors with the pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine scaffold.

Pharmacological intervention of behavioural traits and brain histopathology of prenatal valproic acid-induced mouse model of autism.

Autism spectrum disorder (ASD) is one of the leading causes of distorted social communication, impaired speech, hyperactivity, anxiety, and stereotyped repetitive behaviour. The aetiology of ASD is complex; therefore, multiple drugs have been suggested to manage the symptoms. Studies with histamine H3 receptor (H3R) blockers and acetylcholinesterase (AchE) blockers are considered potential therapeutic agents for the management of various cognitive impairments. Therefore, the aim of this study was to evaluate the neuro-behavioural effects of Betahistine, an H3R antagonist, and Donepezil, an acetylcholinesterase inhibitor on Swiss albino mouse model of autism. The mice were intraperitoneally injected with valproic acid (VPA) on the embryonic 12.5th day to induce autism-like symptoms in their offspring. This induced autism-like symptoms persists throughout the life. After administration of different experimental doses, various locomotor tests: Open Field, Hole-Board, Hole Cross and behavioural tests by Y-Maze Spontaneous Alternation and histopathology of brain were performed and compared with the control and negative control (NC1) groups of mice. The behavioural Y-Maze test exhibits significant improvement (p <0.01) on the short term memory of the test subjects upon administration of lower dose of Betahistine along with MAO-B inhibitor Rasagiline once compared with the NC1 group (VPA-exposed mice). Furthermore, the tests showed significant reduction in locomotion in line crossing (p <0.05), rearing (p <0.001) of the Open Field Test, and the Hole Cross Test (p <0.01) with administration of higher dose of Betahistine. Both of these effects were observed upon administration of acetylcholinesterase inhibitor, Donepezil. Brain-histopathology showed lower neuronal loss and degeneration in the treated groups of mice in comparison with the NC1 VPA-exposed mice. Administration of Betahistine and Rasagiline ameliorates symptoms like memory deficit and hyperactivity, proving their therapeutic effects. The effects found are dose dependent. The findings suggest that H3R might be a viable target for the treatment of ASD.

Molecular Therapeutics in Development to Treat Alzheimer's Disease.

Until recently, only symptomatic therapies, in the form of acetylcholine esterase inhibitors and NMDA-receptor antagonists, have been available for the treatment of Alzheimer's disease. However, advancements in our understanding of the amyloid cascade hypothesis have led to a development of disease-modifying therapeutic strategies. These include immunotherapies based on an infusion of monoclonal antibodies against amyloid-β, three of which have been approved for the treatment of Alzheimer's disease in the USA (one of them, lecanemab, has also been approved in several other countries). They all lead to a dramatic reduction of amyloid plaques in the brain, whereas their clinical effects have been more limited. Moreover, they can all lead to side effects in the form of amyloid-related imaging abnormalities. Ongoing developments aim at facilitating their administration, further improving their effects and reducing the risk for amyloid-related imaging abnormalities. Moreover, a number of anti-tau immunotherapies are in clinical trials, but none has so far shown any robust effects on symptoms or pathology. Another line of development is represented by gene therapy. To date, only antisense oligonucleotides against amyloid precursor protein/amyloid-β and tau have reached the clinical trial stage but a variety of gene editing strategies, such as clustered regularly interspaced short palindromic repeats/Cas9-mediated non-homologous end joining, base editing, and prime editing, have all shown promise on preclinical disease models. In addition, a number of other pharmacological compounds targeting a multitude of biochemical processes, believed to be centrally involved in Alzheimer's disease, are currently being evaluated in clinical trials. This article delves into current and future perspectives on the treatment of Alzheimer's disease, with an emphasis on immunotherapeutic and gene therapeutic strategies.

Components in SLPE Alleviate AD Model Nematodes by Up-Regulating Gene gst-5.

Salvia leucantha is a perennial herb of the genus Salvia in the family Labiatae, which has a wide range of biological activities, mainly including inhibition of acetylcholinesterase, antibacterial, and anti-inflammatory activity. To explore the protective effects and mechanism of action of S. leucantha on Alzheimer's disease (AD), the anti-AD activity of SLE (extracts of S. leucantha) was determined by using a transgenic Caenorhabditis elegans (C. elegans) model (CL4176). Analyses included paralysis assay, phenotypic experiments, transcriptome sequencing, RNA interference (RNAi), heat shock assays, and gas chromatography-mass spectrometry (GC-MS). SLPE (S. leucantha petroleum ether extract) could significantly delay CL4176 paralysis and extend the longevity of C. elegans N2 without harmful effects. A total of 927 genes were significantly changed by SLPE treatment in C. elegans, mainly involving longevity regulatory pathways-nematodes, drug metabolism-cytochrome P450, and glutathione metabolic pathways. RNAi showed that SLPE exerted its anti-AD activity through up-regulation of the gene gst-5; the most abundant compound in SLPE analyzed by GC-MS was 2,4-Di-tert-butylphenol (2,4-DTBP), and the compound delayed nematode paralysis. The present study suggests that active components in S. leucantha may serve as new-type anti-AD candidates and provide some insights into their biological functions.

Evaluating Quinolines: Molecular Dynamics Approach to Assess Their Potential as Acetylcholinesterase Inhibitors for Alzheimer's Disease.

Quinoline represents a promising scaffold for developing potential drugs because of the wide range of biological and pharmacological activities it exhibits. In the present study, quinoline derivatives obtained from CADMA‐Chem docking protocol were investigated in the mean of molecular dynamics simulations as potential inhibitors of acetylcholinesterase enzyme. The examined species can be partitioned between neutral, dq815 (2,3 dihydroxyl‐quinoline‐4‐carbaldehyde), dq829 (2,3 dihydroxyl‐quinoline‐8‐carboxylic acid methane ester), dq1356 (3,4 dihydroxyl‐quinoline‐6‐carbaldehyde), dq1368 (3,4 dihydroxyl‐quinoline‐8‐carboxylic acid methane ester) and dq2357 (5,6 dihydroxyl‐quinoline‐8‐carboxylic acid methane ester), and deprotonated, dq815_dep, dq829_dep, dq1356_dep and dq2357_dep. Twelve molecular dynamics simulations were performed including those of natural acetylcholine, of the well‐known donepezil inhibitor and of the founder quinoline chosen as reference. Key intermolecular interactions were detected and discussed to describe the different dynamic behavior of all the considered species. Binding energies calculation from MMPBSA well accounts for the dynamic behavior observed in the simulation time proposing dq1368 as promising candidate for the inhibition of acetylcholinesterase. Retrosynthetic route for the production of the investigated compounds is also proposed.

A Novel Tetrahydroacridine Derivative with Potent Acetylcholinesterase Inhibitory Properties and Dissociative Capability against Aβ42 Fibrils Confirmed by In Vitro Studies.

Alzheimer's disease (AD) is one of the most common causes of dementia, accounting for more than 60% of all cases. It is a neurodegenerative disease in which symptoms such as a decline in memory, thinking, learning, and organizing skills develop gradually over many years and eventually become more severe. To date, there is no effective treatment for the cause of Alzheimer's disease, and the existing pharmacological options primarily help manage symptoms. Treatment is mainly based on acetylcholinesterase (AChE) inhibitors such as donepezil, rivastigmine, and galantamine, which exhibit numerous adverse cardiovascular and gastrointestinal effects due to excessive stimulation of peripheral cholinergic activity involving muscarinic receptors. Therefore, in addition to the obvious drugs that act on the cause of the disease, new drugs based on AChE inhibition that show the fewest side effects are needed. One potential drug could be a new compound under study, tetrahydroacridine derivative (CHDA), which showed significant potential to inhibit the AChE enzyme in previous in vitro studies. The present study shows that while having very potent AChE inhibitory properties, CHDA is a compound with low toxicity to nerve cell culture and living organisms. In addition, it exhibits dissociative activity against amyloid β fibrils, which is extremely important for applications in Alzheimer's disease therapy.

Discovery of thiourea based acetylcholinesterase inhibitors and antibacterial agents: Synthesis, in vitro, structure-activity relationship and in silico study

In current work, we have synthesized a novel class of compounds (1-6) and assessed their acetylcholinesterase and antibacterial investigations to find out the most potent analogs. In this series, only two analogs were found to be the most potent against acetylcholinesterase and antibacterial activity. Analog (1, 25.35 ± 0.21 µM for acetylcholinesterase, ZOI 18.167 ± 0.7638 mm & MIC 149 μg/cm3 for antibacterial) & (6, 45.81 ± 0.02 µM acetylcholinesterase, ZOI 13.10 ± 0.5568 mm & MIC 180 μg/cm3 for antibacterial) shown to be the highest activity against both of them. In order to investigate the binding affinity of active residue molecular docking study. While the docking score energy for compounds 5, and 6 were the highest ones obtained for compound 5 was -8.2214 kcal/mol with an RMDS refine of 1.5843, while compound 6 was -8.0047 kcal/mol, with an RMDS refine of 1.3806.All of the above results confirm the analogue 5 & 6 are index as more potent than the others. Furthermore, all of the synthesized are characterized through modern spectroscopic techniques such as NMR and FTIR. In the future these are further assessed their cytotoxic effects and many more.

Some Novichok agents and their interactions with Zn+2 ion. A DFT study

The Novichok agents attracted attention, especially in the Soviet Union in order to synthesize very effective warfare chemicals. They belong to the class of organophosphate acetyl cholinesterase inhibitors. In the present study, of those agents A-230, A-232, A‑234, A-242 and A-262 have been considered within the restrictions of density functional theory at the level of B3LYP/6-31++G(d,p). Also the Zn+2 composites of those agents have been considered. All the structures are electronically stable, thermodynamically exothermic and have favorable Gibbs’ free energy of formation values at the standard states. Various quantum chemical properties of them, including UV-VIS spectra, the HOMO and LUMO energies etc., have been obtained and discussed.

Fluorescent Iron-Doped Polymer Dot Nanozyme-Based Cascade System for Dual-Mode Detection of Acetylcholinesterase Activity and Its Inhibitors.

The advancement of acetylcholinesterase (AChE) activity and its inhibitor assays is crucial for clinical diagnosis, drug screening, and environmental monitoring. A nanozyme-mediated cascade reaction system could offer promising prospects for a wide range of applications in such biosensing; however, the creation of nanozyme catalysts with diverse functionalities remains a significant challenge. Herein, we have proposed a multifunctional iron-doped polymer dots (Fe-PDs) nanozyme possessing excellent fluorescence and peroxidase (POD)-mimicking activity. Notably, the Fe-PDs nanozyme is capable of catalyzing H2O2 to produce a series of reactive oxygen species, which can simultaneously quench the fluorescence of Fe-PDs and induce a chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB), enabling the dual-mode detection of H2O2 through both fluorescence turn-off and absorbance turn-on signals. Furthermore, by integrating acetylcholine (ACh) and choline oxidase (ChOx), we have developed a three-enzyme (AChE-ChOx-POD) cascade-based fluorometric and colorimetric dual-mode sensing platform for monitoring AChE activity and its inhibitors. The sensitive and convenient dual-mode sensor has achieved low limits of detection with 0.5 mU/mL (fluorometry) and 0.014 mU/mL (colorimetry) for AChE, respectively, which are superior to the traditional Ellman's assay. More significantly, this sensor can also be extended to detect the reversible and irreversible inhibitors of AChE, such as tacrine (IC50 = 23.3 nM) and carbaryl (LOD = 0.8 nM). We firmly believe that this innovative dual-mode nanozyme-involved multienzyme cascade system-based sensing strategy will stimulate further exploration and serve as a versatile and practical tool for biochemical sensing applications.

Protective effects of betanin, a novel acetylcholinesterase inhibitor, against H2O2-induced apoptosis in PC12 cells.

Dysfunction of the cholinergic system and increased oxidative stress have a crucial role in cognitive disorders including Alzheimer's disease (AD). Here, we have investigated the protective effects of betanin, a novel acetylcholinesterase (AChE) inhibitor, on hydrogen peroxide (H2O2)-induced cell death in PC12 cells. The protective effects were assessed by measuring cell viability, the amount of reactive oxygen species (ROS) production, AChE activity, cell damage, and apoptosis using resazurin, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), Ellman method, lactate dehydrogenase (LDH) release, propidium iodide (PI) staining and flow cytometry, and Western blot analysis. H2O2 (150µM) resulted in cell viability reduction and apoptosis induction while, pretreatment with the betanin (10, 20, and 50μM) and N-Acetyl-L-cysteine (NAC) (2.5 and 5mM) significantly increased the viability (P < 0.05, P < 0.01 and P < 0.001) and at 5-50μM betanin decreased ROS amount (P < 0.05, P < 0.01 and P < 0.001). Whereas, pretreatment with the betanin (10, 20, and 50μM) decreased AChE activity (P < 0.001), also at 20 and 50μM betanin reduced the release of LDH (P < 0.001), and at 10-50μM decreased the percentage of apoptotic cells (P < 0.001). Apoptosis biomarkers such as cleaved poly (ADP-ribose) polymerase (PARP) (P < 0.01 and P < 0.001) and cytochrome c (P < 0.05 and P < 0.001) were attenuated after pretreatment of PC12 cells with betanin at 10-20μM and 10-50μM respectively. Indeed, survivin (P < 0.001) increased after pretreatment of cells with betanin at 10-20μM. Overall, betanin may use the potential to delay or prevent cell death caused by AD through decreasing the activity of AChE as well as attenuating the expression of proteins involved in the apoptosis pathway.

Biosynthesis and biological activities of magnesium hydroxide nanoparticles using Tinospora cordifolia leaf extract.

The synthesis of magnesium hydroxide nanoparticles (Mg(OH)2 NPs) using plant extracts are known to be a practical, economical, and an environmentally friendly approach. In this work, Mg(OH)2 NPs were synthesized using aqueous leaf extract of Tinospora cordifolia, a medicinal plant commonly found in India. The synthesized Mg(OH)2 NPs were characterized using various spectroscopic techniques. The ultraviolet-visible (UV-Vis) absorption peak of the Mg(OH)2 NPs was detected at 289nm, Fourier transform infrared (FTIR) analysis confirmed the presence of various functional groups, and X-ray diffraction (XRD) patterns revealed the well-crystallized structure of the Mg(OH)2 NPs. High-resolution transmission electron microscopy (HR-TEM) and scanning electron microscopy (SEM) analyses depicted spherical morphology and an average particle size (PS) of 27.71nm. The energy-dispersive X-ray (EDX) analysis confirmed the presence of C, O, and Mg elements, and the X-ray photoelectron spectroscopy (XPS) survey spectrum confirmed the elements for the Su 1s peak at 280.2eV. The dynamic light scattering (DLS) analysis displayed an average PS of 54.3nm, and the Zeta potential (ZP) was of 9.89mV. The fabricated Mg(OH)2 NPs displayed notable antibacterial activity against S. epidermidis, E. coli, and S. aureus. In addition, these NPs exhibited strong antioxidant properties (> 75%) based on DPPH, ABTS, and hydrogen peroxide (H2O2) assays. Further, the same NPs exerted a potent anti-inflammatory activity (> 65%) based on COX-1 and COX-2 evaluations. The anti-Alzheimer' disease (AD) potential of Mg(OH)2 NPs was assessed through effective inhibition (> 70%) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. Molecular docking (MD) studies confirmed that caryophyllene has higher binding affinity with AChE (-5.3kcal/mol) and BuChE (-6.4kcal/mol) enzymes. This study emphasizes the green synthesis of Mg(OH)2 NPs using T. cordifolia as a plant source and highlights their potential for biomedical applications.