Insight into antioxidant-like activity and computational exploration of identified bioactive compounds in Talinum triangulare (Jacq.) aqueous extract as potential cholinesterase inhibitors.

BACKGROUND: Recent reports have highlighted the significance of plant bioactive components in drug development targeting neurodegenerative disorders such as Alzheimer's disease (AD). Thus, the current study assessed antioxidant activity and enzyme inhibitory activity of the aqueous extract of Talinum triangulare leave (AETt) as well as molecular docking/simulation of the identified phytonutrients against human cholinesterase activities. METHODS: In vitro assays were carried out to assess the 2,2- azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) cation radicals and cholinesterase inhibitory activities of AETt using standard protocols. High performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was employed to identify compounds in AETt. Also, for computational analysis, identified bioactive compounds from AETt were docked using Schrodinger's GLIDE against human cholinesterase obtained from the protein data bank ( https://www.rcsb.org/ ). RESULTS: The results revealed that AETt exhibited a significant concentration-dependent inhibition against ABTS cation radicals (IC50 = 308.26 ± 4.36 µg/ml) with butylated hydroxytoluene (BHT) as the reference. Similarly, AETt demonstrated a significant inhibition against acetylcholinesterase (AChE, IC50 = 326.49 ± 2.01 µg/ml) and butyrylcholinesterase (BChE, IC50 = 219.86 ± 4.13 µg/ml) activities with galanthamine as the control. Molecular docking and simulation analyses revealed rutin and quercetin as potential hits from AETt, having showed strong binding energies for both the AChE and BChE. In addition, these findings were substantiated by analyses, including radius of gyration, root mean square fluctuation, root mean square deviation, as well as mode similarity and principal component analyses. CONCLUSION: Overall, this study offers valuable insights into the interactions and dynamics of protein-ligand complexes, offering a basis for further drug development targeting these proteins in AD.

In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected Berberis Species.

Berberis species have a long history of use in traditional Chinese medicine, Ayurvedic medicine, and Western herbal medicine. The aim of this study was the quantification of the main isoquinoline alkaloids in extracts obtained from various Berberis species by HPLC, in vitro and in silico determination of anti-cholinesterase activity, and in vitro and in vivo investigations of the cytotoxic activity of the investigated plant extracts and alkaloid standards. In particular, Berberis species whose activity had not been previously investigated were selected for the study. In the most investigated Berberis extracts, a high content of berberine and palmatine was determined. Alkaloid standards and most of the investigated plant extracts exhibit significant anti-cholinesterase activity. Molecular docking results confirmed that both alkaloids are more favourable for forming complexes with acetylcholinesterase compared to butyrylcholinesterase. The kinetic results obtained by HPLC-DAD indicated that berberine noncompetitively inhibited acetylcholinesterase, while butyrylcholinesterase was inhibited in a mixed mode. In turn, palmatine exhibited a mixed inhibition of acetylcholinesterase. The cytotoxic activity of berberine and palmatine standards and plant extracts were investigated against the human melanoma cell line (A375). The highest cytotoxicity was determined for extract obtained from Berberis pruinosa cortex. The cytotoxic properties of the extract were also determined in the in vivo investigations using the Danio rerio larvae xenograft model. The obtained results confirmed a significant effect of the Berberis pruinosa cortex extract on the number of cancer cells in a living organism. Our results showed that extracts obtained from Berberis species, especially the Berberis pruinosa cortex extract, can be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of neurodegenerative diseases and human melanoma.

Variability of Isoquinoline Alkaloid Profiles and Anticholinesterase Activities with Binding-Mode Predictions of Glaucium flavum Population.

In this study, phytochemical and biological activity studies supported by docking were carried out on a species of the genus Glaucium, a repository of isoquinoline alkaloids. The GC-MS (Gas Chromatography-Mass Spectrometry) method is used to characterize the isoquinoline alkaloids of Glaucium flavum Crantz. (Papaveraceae). G. flavum was collected from seven different regions of Türkiye (Antalya, Urla-Izmir, Mordogan-Izmir, Mugla, Assos-Canakkale, Karabiga-Canakkale, Giresun) and totally 17 compounds were detected by GC-MS. Glaucine was found to be the major constituent in the sample collected from Mugla, whereas isocorydine was recorded to be the principal alkaloid in other samples. Further fractionation studies on G. flavum collected from Antalya province in Southwestern Türkiye, yielded five major alkaloids (isocorydine 1, dihydrosanguinarine 2, glaucine 3, dehydroglaucine 4, protopine 5) which were characterized by spectroscopic methods. Anticholinesterase activities of the extracts and isolated alkaloids were also tested by in vitro Ellman method. The isolated compounds were also analyzed by a molecular docking technique to determine the binding orientations in the gorge of the active site of acetylcholinesterase (AChE) and a homology model of butyrylcholinesterase (BuChE). This is the first comparative investigation of the phytochemical composition and biodiversity of Glaucium flavum species growing in Türkiye.

The protective effect of methanolic extract of Verbascum cheiranthifolium and Biebersteinia multifida DC on hippocampus damage induced by diazinon in male Wistar rats: An experimental study.

Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.

Design, synthesis and biological evaluation of bakuchiol derivatives as multi-target agents for the treatment of Alzheimer's disease.

The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ± 2.00 µM) and compound 3n (IC50 = 34.78 ± 0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.

In vitro and in silico cholinesterase inhibitory and antioxidant effects of essential oils and extracts of two new Salvia fruticosa mill. cultivars (Turgut and Uysal) and GC-MS analysis of the essential oils.

The EtOH extracts of the leaves of two new cultivars (Uysal-SFU and Turgut-SFT) of Salvia fruticosa Mill. was tested against acetylcholinesterase (IC50: 30.62 ± 3.27 and 32.97 ± 2.33 µg/mL for SFU and SFT, respectively) and butyrylcholinesterase (IC50: 69.91 ± 1.08 µg/mL and 86.55 ± 1.26 µg/mL), respectively, relevant to Alzheimer's disease. The essential oils showed a stumpy inhibition against AChE and no inhibition against BChE. DPPH radical scavenging activity of the extracts (86.70 ± 0.17% and 86.14 ± 1.13% for SFU and SFT, respectively) was stronger than that of quercetin (85.51 ± 0.17%): Their (1.24 ± 0.05 and 1.04 ± 0.16 for SFU and SFT, respectively) ferric-reducing antioxidant power were close to that of the reference (e.g. quercetin, 1.42 ± 0.14). Molecular docking simulations were performed on their major monoterpenes. Our findings revealed that the leaf EtOH extracts of two cultivars are promising inhibitors of both AChE and BChE.

2D-QSAR, molecular docking and MD simulation based virtual screening of the herbal molecules against Alzheimer's disorder: an approach to predict CNS activity.

Acetylcholinesterase (AChE) is one of the key enzyme targets that have been used clinically for the management of Alzheimer's Disorder (AD). Numerous reports in the literature predict and demonstrate in-vitro, and in-silico anticholinergic activity of herbal molecules, however, majority of them failed to find clinical application. To address these issues, we developed a 2D-QSAR model that could efficiently predict the AChE inhibitory activity of herbal molecules along with predicting their potential to cross the blood-brain-barrier (BBB) to exert their beneficial effects during AD. Virtual screening of the herbal molecules was performed and amentoflavone, asiaticoside, astaxanthin, bahouside, biapigenin, glycyrrhizin, hyperforin, hypericin, and tocopherol were predicted as the most promising herbal molecules for inhibiting AChE. Results were validated through molecular docking, atomistic molecular dynamics simulations and Molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) studies against human AChE (PDB ID: 4EY7). To determine whether or not these molecules can cross BBB to inhibit AChE within the central nervous system (CNS) for being beneficial for the management of AD, we determined a CNS Multi-parameter Optimization (MPO) score, which was found in the range of 1 to 3.76. Overall, the best results were observed for amentoflavone and our results demonstrated a PIC50 value of 7.377 nM, molecular docking score of -11.5 kcal/mol, and CNS MPO score of 3.76. In conclusion, we successfully developed a reliable and efficient 2D-QSAR model and predicted amentoflavone to be the most promising molecule that could inhibit human AChE enzyme within the CNS and could prove beneficial for the management of AD.Communicated by Ramaswamy H. Sarma.

N-Methylneolitsine as a new and potent acetylcholinesterase inhibitor of Cissampelos pareira Linn. aerial parts: bioassay-guided isolation and quantitative densitometric analysis.

The rising geriatric population is expected to increase the demand for drugs treating neurodegenerative diseases. The present work is aimed to discover acetylcholinesterase (AChE) inhibitors from Cissampelos pareira Linn. aerial parts (Family: Menispermaceae). Bioassay-guided isolation, AChE inhibition study and estimation of the therapeutic marker in different parts of raw herbs were conducted. The structure of the compound (1) was elucidated as N-methylneolitsine by using NMR (1D and 2D) and ESI-MS/MS spectral data, which is a new natural analogue of neolitsine. It showed good AChE inhibition with an IC50 value of 12.32 µg/mL. It was densitometrically estimated to be 0.074 - 0.33% in aerial parts of C. pareira, collected from various locations. The alkaloid reported here could be potentially useful for the treatment of various neurodegenerative diseases and the aerial part of C. pareira could be used as a promising ingredient for various preparations treating neurodegenerative diseases.

Five new biflavonoids with acetylcholinesterase inhibitory activity from Diphylleia sinensis.

Five new biflavonoids, diphybiflavonoids A - E (1-5), were isolated from the roots and rhizomes of Diphylleia sinensis. Their structures were elucidated by extensive spectroscopic data, including UV, IR, HR-ESI-MS and 2D NMR. Their absolute configurations were determined by ECD spectra. All isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activity. Compounds 1-4 exhibited the potent AChE inhibitory activities with IC50 values of 1.62, 2.10, 2.08, and 5.15 µM, respectively. The preliminary structure-activity relationship study indicated that the connection mode (C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''') of biflavonoid subunits, and 3-hydroxy group of flavonol subunit were important structural factors for AChE inhibitory activity. Biflavonoids, containing a C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''' linkage, can be a potentially useful platform for development of cholinesterase inhibitors.

Aromatic glycosides and lignans glycosides with their acetylcholinesterase inhibitory activities from the leaves of Picrasma quassioides.

In this study, eight new natural products were isolated from the leaves of Picrasma quassioides. Spectroscopic techniques were used for the elucidation of their planar structures. Their absolute configurations were elucidated on the basis of electron circular dichroism (ECD) techniques combined with the P/M helicity rule for the 2,3-dihydrobenzofuran chromophore, and saccharide hydrolysis. Cholinesterase inhibitors are often used as Alzheimer's disease inhibitors.Thus, acetylcholinesterase and butyrylcholinesterase inhibitory activity of these eight compounds were tested, and results showed that only compound 6 showed weakly acetylcholinesterase inhibitory activity. In particular, molecular docking was used to illustrate the bindings between compound 6 and the active sites of AChE.

Amaryllidaceae alkaloids from the bulbs of Crinum latifolium L. and their cholinesterase inhibitory activities.

Eleven previously undescribed Amaryllidaceae alkaloids, crinalatifolines A-K (1-11), and two first naturally occurring alkaloids, dihydroambelline (12) and N-demethyldihydrogalanthamine (13), were isolated from the bulbs of Crinum latifolium L. Additionally, thirty-seven known alkaloids and one alkaloid artifact were also isolated from this plant species. Their structures and absolute configurations were elucidated using extensive spectroscopic techniques, including IR, NMR, MS, and ECD. Evaluations of the cholinesterase inhibitory activities of most of these compounds were conducted. Among the tested compounds, ungeremine exhibited the highest potency against acetylcholinesterase and butyrylcholinesterase, with the IC50 values of 0.10 and 1.21 µM, respectively. These values were 9.4- and 2.4-fold more potent than the reference drug galanthamine.

Nanoplasmonic biosensors for multicolor visual analysis of acetylcholinesterase activity and drug inhibitor screening in point-of-care testing.

The monitoring of acetylcholinesterase (AChE) activity and the screening of its inhibitors are significance of the diagnosis and drug therapy of nervous diseases. A metal ions-mediated signal amplification strategy was developed for the highly sensitive and multicolor assay of AChE activity and visually screening its drug inhibitors. After the specific reaction between AChE and acetylthiocholine (ATCh), the hydrolysis product thiocholine (TCh) can directly and decompose the α-FeOOH nanorods (NRs) to release amounts of Fe2+, which was regarded as Fenton reagent to efficiently catalyze H2O2 to produce ·OH. Then, the as-formed ·OH can further largely shorten the gold nanobipyramids (Au NBPs), generating a series of palpable color variations. The linear range for AChE activity was 0.01-500.0 U/L with the limit of detection as low as 0.0074 U/L. The vivid visual effects could be easily distinguished for the multicolor assay of AChE activity by naked eye in visible light. To achieve the point-of-care testing, Au NBPs were further assembled on polymeric electrospun nanofibrous films (ENFs) surface as test strips for the easy-to-use test of AChE activity by RGB values with a smartphone. Fascinatingly, this proposed strategy can be used for the visual screening AChE inhibitors or non-inhibitors. Comparing with the clinical drugs (rivastigmine tartrate, and donepezil), some natural alkaloids such as evodiamine, caffeine, camptothecin, and berberine hydrochloride were selected as inhibitor modes to confirm the drug screening capability of this method. This proposed strategy may have great potential in the other disease-related enzymatic biomarkers assay and the rapid screening of drug therapy.

Anthemis tricolor Containing Unusual Totarol with Cytotoxic and Acetylcholinesterase-Inhibitory Activity.

Anthemis tricolor is an endemic species of Cyprus, and there is very limited information on its chemistry and pharmacological activities. The study aims to identify the in-vitro cytotoxic and acetylcholinesterase activities of Anthemis tricolor. The compounds responsible for the activities were also identified. Potent extracts of A. tricolor were subjected to preparative isolation and spectral structure determination studies. The chloroform extract contained many components, and due to the small quantity of extract available, enough pure compound(s) cannot be obtained for structure determination studies, though the n-hexane extract afforded two known compounds, totarol (1) and taraxasterol (2). The structures of the compounds (1 and 2) were determined by 1 H and 13 C NMR experiments. The pure compounds were also tested for their acetylcholinesterase inhibitory properties. For compound 1, the IC50 value was found to be 87.88 µg/mL. However, no inhibition was seen for 2. Anthemis tricolor was established to be a valuable source of pharmacologically active compounds and requires further studies.

In Vitro Antibacterial, Antioxidant, Anticholinesterase, and Antidiabetic Activities and Chemical Composition of Salvia balansae.

CONTEXT: Salvia balansae de Noé (S. balansae) (Lamiaceae) is known to be an important plant used in folk medicine as an herbal remedy in Algeria. OBJECTIVE: The purpose of the present study was to demonstrate the phytochemical composition, antioxidant activities, enzyme inhibitory activities, and antimicrobial activities of S. balansae extracts. MATERIALS AND METHODS: A methanolic extract and a petroleum ether extract from the aerial parts of the plant were assessed for their chemical composition. HPLC-MS and HPLC-DAD assessed the content of phenols, GC-MS the fatty acid composition, and ICP-MS the mineral profiles of the plant. Additionally, we evaluated the bioactivities of S. balansae extracts by the DPPH, ABTS, and CUPRAC assays, including the antioxidant potential against AChE, BChE, α-amylase, and α-glucosidase for enzyme inhibition. The antibacterial and antifungal activities of the methanolic extract were determined by the disc diffusion test against several strains of bacteria and yeasts. RESULTS: Our findings revealed that the aerial parts of S. balansae were rich in phytochemical components and contained large amounts of minerals. Quantitative analysis of phenolic compounds by HPLC-DAD revealed the presence of 12 compounds in three major classes, flavonoids, hydroxycinnamic acid, and phenolic acid derivatives, with 0.61, 0.45, and 0.29 mg/g of extract, respectively. Nine phenolic constituents were quantified by HPLC-MS analysis; catechin (72.5%) was the main compound, followed by myricetin (21.7%). The fatty acid composition of the S. balansae petroleum ether extract by GC-MS analysis was quantified. Seventeen compounds, including palmitic acid, were identified as the major fatty acids. The antioxidant activity of the S. balansae extracts was measured by three different methods: the methanol extract provided better results than the petroleum ether extract, and interesting values were noted for the DPPH, ABTS, and CUPRAC assays of 242.7 ± 7.44, 124.1 ± 9.70, and 222.9 ± 6.05 µg/mL, respectively. The enzyme inhibition activity of the plant could not be determined. The antimicrobial results of the methanolic extract obtained from the disc diffusion method, followed by measurements of MIC, MBC, and MFC against several bacteria and yeasts, indicated that S. balansae exhibited noticeable antimicrobial and antifungal activities. CONCLUSIONS: These results provided new data about the main phenolic compounds and biological activities of extracts of the aerial parts of S. balansae, which might be an alternative source for synthetic bioactive compounds.

Pharmacological and toxicological effects of Amaryllidaceae.

The Amaryllidaceae family is widely distributed in the tropics, presenting biological activity attributed mostly to alkaloids, such as an important inhibitory activity of acetylcholinesterase (AChE), antifungal, antibacterial, and cytotoxic activities. The present study aims to review the spectrum of action of the main biological activities and toxicity of secondary metabolites found in Amaryllidaceae through a literature review, using Prisma and the descriptors "Pharmacological effects of Amaryllidaceae" and "Amaryllidaceae family" and "Pharmacological actions of Amaryllidaceae", used in English and Portuguese. The literature search was done in March and May 2023. Original works published from 2012 to 2023, available in full, and presenting experimental and clinical studies were included. After the selection considering the inclusion and exclusion criteria, 60 articles fulfilled the defined criteria. From a pharmacological point of view, the highlight is due to the alkaloid galantamine, which has the potential- and is already used - for treating Alzheimer's. The toxicological aspect must be considered and evaluated carefully, as alkaloids have been associated with adverse effects such as nausea, vomiting, diarrhea, abdominal pain, and cardiovascular, neurological, and respiratory changes. Furthermore, some studies indicate that consuming these plants in significant quantities can lead to hepatic and renal toxicity. Therefore, the therapeutical use of this family's plant drugs and derivatives requires further studies to elucidate its effects and point out metabolites with therapeutic potential.

Neuroprotective evaluation of diospyrin against drug-induced Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC50 values of 95 µg/mL for AChE and 110 µg/mL for BChE as compared to the standard drug donepezil (IC50: 95 & 85 µg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC50: 139.74 µg/mL) of DPPH-free radicals at the highest concentration of 1000 µg/mL as compared to the ascorbic acid (IC50: 13.72 µg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.

Antioxidant and anti-Alzheimer activities of Clivia miniata (Lindl) roots, bulbs, and aerial parts: In-vitro and in-silico studies.

Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports revealed a direct role of oxidative stress in the early stage of Alzheimer's disease (AD). Meanwhile, ß-site amyloid precursor protein cleavage enzyme 1 (BACE-1) is a molecular target for the treatment of AD. We aimed to investigate C. miniata root, bulb, and aerial part chemical profiling, antioxidant, BACE-1, and AChE enzyme inhibitory activities. Results showed that the total root had the most potent radical scavenging activity as compared to the total bulb and aerial part, respectively. Ethanol root extract had the most potent BACE-1 inhibitory activity (IC50 = 0.02 ± 0.001 µg/mL) as compared to the bulb and aerial part (IC50 = 0.93 ± 0.13, 1.80 ± 0.24 µg/mL), respectively. Moreover, the total root extract mitigated AChE enzyme activity more than total bulb and aerial fractions with IC50 values of (0.06 ± 0.02, 0.58 ± 0.3, and 1.89 ± 0.42 µg/mL, respectively. Bioassay-guided acid-base fractionation confirmed superior BACE-1 inhibitory activity of the root fractions particularly, methylene chloride and ethyl acetate fractions with (IC50 values of 0.21 ± 0.60 and 0.01 ± 0.001 µg/mL), respectively. UPLC-MS analysis of ethyl acetate and methylene chloride fractions of C. miniata root led to the identification of eight phenolics and thirteen alkaloids, respectively. Molecular docking studies against BACE-1 protein revealed that lycorine di-hexoside, miniatine, and cliviaaline were the most promising hits. Further investigation of anti-AD potential of the aforementioned small molecules is required.

Exploring Medicinal Herbs' Therapeutic Potential and Molecular Docking Analysis for Compounds as Potential Inhibitors of Human Acetylcholinesterase in Alzheimer's Disease Treatment.

Background and Objectives: Alzheimer's disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods: Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski's rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (-8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders.

Metabolomic Analysis and in Vitro Investigation of the Biological Properties of a By-Product Derived from Vicia faba.

By-products from plant sources are recently regarded as a valuable source of bioactive compounds. In this regard, the present study aims to assess the bioactivities of the 70 % MeOH extract obtained from Vicia faba peels and analyze its metabolomic profile. Acetylcholinesterase and carbohydrate metabolizing enzymes inhibitory activities of the plant extract were assayed using quantitative colorimetric tests. Antioxidant activity was estimated by DPPH assay, and cytotoxic activity was evaluated against normal fibroblast skin cells (1-BJ1). Ninety-one metabolites were tentatively identified using ultra-high-performance liquid chromatography (UHPLC) hyphenated with quadrupole-time-of-flight tandem mass spectrometry (QTOF-MS). Most of these compounds were described for the first time in the plant. In addition, catechin, rutin, quercitrin, and rhamnetin were isolated from the plant extract. The plant extract and the isolated compounds possessed no cytotoxic activity on (1-BJ1), while they exhibited anticholinesterase with the highest activity for 70 % MeOH extract (IC50 =120.11 mg/L), antioxidant potential with the highest activity for rutin (90.54±0.73 %), and carbohydrate metabolizing inhibitory activities with the highest activity for rutin. These discoveries imply that V. faba peels might serve as an efficient antioxidant, exhibit anticholinesterase properties, and have the potential for use in managing diabetes, all while avoiding cytotoxicity in normal cells.