Natural acetylcholinesterase inhibitors: A multi-targeted therapeutic potential in Alzheimer's disease

Gajendra, Kumar; Pratap, G.K.; Poornima, D.V.; Shantaram, Manjula; Ranjita, G.

doi:10.1016/j.ejmcr.2024.100154

Cited by 9 publications

(2 citation statements)

References 143 publications

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“…Moreover, lupeol significantly reduced AChE activity in LPS-induced neuroinflammation model of Alzheimer’s disease like pathologies. These results provide the neuroprotective role of lupeol and its therapeutic potential in regulating cholinergic dysfunctions in AD ( 71 , 72 ).…”

Section: Discussionmentioning

confidence: 77%

Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus

Choe,

Park,

Park

et al. 2024

Front. Nutr.

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Neuroinflammation includes the activation of immune glial cells in the central nervous system, release pro-inflammatory cytokines, which disrupt normal neural function and contribute to various neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and stroke. AD is characterized by various factors including amyloidogenesis, synaptic dysfunction, memory impairment and neuroinflammation. Lipopolysaccharide (LPS) constitutes a vital element of membrane of the gram-negative bacterial cell, triggering vigorous neuroinflammation and facilitating neurodegeneration. Lupeol, a naturally occurring pentacyclic triterpene, has demonstrated several pharmacological properties, notably its anti-inflammatory activity. In this study, we evaluated the anti-inflammatory and anti-Alzheimer activity of lupeol in lipopolysaccharide (LPS)-injected mice model. LPS (250ug/kg) was administered intraperitoneally to C57BL/6 N male mice for 1 week to induce neuroinflammation and cognitive impairment. For biochemical analysis, acetylcholinesterase (AChE) assay, western blotting and confocal microscopy were performed. AChE, western blot and immunofluorescence results showed that lupeol treatment (50 mg/kg) along with LPS administration significantly inhibited the LPS-induced activation of neuroinflammatory mediators and cytokines like nuclear factor (NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase (COX-2) and interleukin (IL-1β). Furthermore, we found that LPS-induced systemic inflammation lead to Alzheimer’s symptoms as LPS treatment enhances level of amyloid beta (Aβ), amyloid precursor protein (APP), Beta-site APP cleaving enzyme (BACE-1) and hyperphosphorylated Tau (p-Tau). Lupeol treatment reversed the LPS-induced elevated level of Aβ, APP, BACE-1 and p-Tau in the hippocampus, showing anti-Alzheimer’s properties. It is also determined that lupeol prevented LPS-induced synaptic dysfunction via enhanced expression of pre-and post-synaptic markers like SNAP-23, synaptophysin and PSD-95. Overall, our study shows that lupeol prevents memory impairment and synaptic dysfunction via inhibition of neuroinflammatory processes. Hence, we suggest that lupeol might be a useful therapeutic agent in prevention of neuroinflammation-induced neurological disorders like AD.

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Section: Discussionmentioning

confidence: 77%

Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus

Choe,

Park,

Park

et al. 2024

Front. Nutr.

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“…Another study by Karakaya et al (2019) [ 113 ] found that oxypeucedanin isolated from parts of Angelica purpurascens also had high antioxidant and anticholinesterase activities, thereby supporting the results of our study. Acetylcholinesterase (AChE) has been proposed as a potential target for AD treatment due to evidence showing that inhibiting its activities can lead to improvement in the condition [ [114] , [115] , [116] ]. However, our investigation did not indicate any interaction between oxypeucedanin and AChE, so we did not explore this further.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the anti-Alzheimer potential of bioactive compounds from Citrus hystrix DC. peel, leaf, and essential oil by network pharmacology

Putri,

Utomo,

Tunjung

et al. 2024

Heliyon

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Arisarum vulgare: Bridging Tradition and Science Through Phytochemical Characterization and Exploring Therapeutic Potential via In vitro, In vivo, and In silico Biological Activities

Bouafia,

Boudjelal,

Bouaziz‐Terrachet

et al. 2024

ChemistrySelect

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Arisarum vulgare O. Targ. Tozz. (Araceae), locally known as “Elbgouga,” holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, cancer, skin problems, eczema, wounds, and burns. The aim of this study was to explore for the first time the phytochemical profile, antioxidant, antibacterial, and inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, DNA protection, and capacity to promote wound healing. Preliminary phytochemical experiments were conducted to evaluate the major classes of bioactive compounds, in addition to the total phenol and flavonoid amounts in AVEE. An LC‐MS/MS analysis was conducted to clarify the phytochemical composition of this particular botanical species. The antioxidant capacity was assessed using DPPH· and ABTS·+ radical scavenging tests. The agar diffusion approach was used to ascertain the antibacterial efficacy against four bacteria (Staphylococcus aureus, Enterococcus faecium, Escherichia coli, and Salmonella typhimurium). Cholinesterase inhibition was evaluated using a colorimetric method that relies on Ellman's reaction. The protective effects of AVEE on pBR322 plasmid DNA damaged by H2O2 and UV treatment were assessed by their DNA‐breaking forms. The in vivo acute dermal toxicity and wound healing potential of the AVEE ointment (1–5% AVEO) were also investigated, and histological analyses were carried out on biological samples. Five protein targets were the subject of an in silico molecular docking investigation (TNFα, TGFBR1, IL‐1ß, GSK‐3ß, and NOS) and ADMET studies of the main components of the extracts were performed. The screening of phytochemicals revealed a significant concentration of phenolic compounds (176.00 ± 1.08 mg of gallic acid equivalents/g of dry extract), mainly flavonoids (81.21 ± 1.24 mg of quercetin equivalents/g of dry extract). Three major compounds were identified by LC‐MS/MS analysis, belonging mainly to the class of flavonoids, with rutin as the most abundant compound (11.85 mg/g extract), followed by hesperidin (4.125 mg/g extract). A conspicuous presence of isoquercitrin (1.327 mg/g extract) was also found. Small amounts of flavonoids and phenolic acids were also detected (catechin, chlorogenic acid, syringic acid, salicylic acid, kaempferol, and luteolin). DPPH assay showed higher antioxidant capacity compared to the ABTS·+ assay (142.60 ± 5.52 µg/mL and 236.10 ± 0.22 µg/mL, respectively). AVEE was effective against all selected bacterial strains; however, the highest zone of inhibition (36.00 ± 0.1 mm) was noted against E. faecium. The extract of the plant significantly inhibited both AChE and BChE (89.98 ± 18.76 µg/mL inhibitory activity against AChE and 98.28 ± 44.68 µg/mL inhibitory activity against BChE, respectively). The ethanolic extract of A. vulgare and quercetin exhibited more significant DNA protection action in form I, with percentages of 90.41 and 94.23%, respectively, compared to form II, where the percentages were 27.91 and 51.92%, respectively. The AVEO formulation may be safely administered by topical application. A statistically significant wound contraction was discovered in the group treated with 5% AVEO compared to the groups that were not treated or treated with petroleum jelly. Furthermore, there was no notable disparity detected between the group treated with 5% AVEO and the group treated with the reference drug. The 5% AVEO‐treated group showed, after the research was complete, the most significant percentage of wound contraction (96.90 ± 0.42%). Moreover, the topical application of the formulation improved histological parameters. In silico study showed that rutin, hesperidin, and isoquercitrin had a high affinity to the five main targets that might contribute to the wound healing potential of A. vulgare ethanolic extract. The impressive biological capabilities of A. vulgare indicate that the plant has the ability to be a valuable source of bioactive chemicals with various medical applications.

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Natural acetylcholinesterase inhibitors: A multi-targeted therapeutic potential in Alzheimer's disease

Cited by 9 publications

References 143 publications

Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus

Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus

Analysis of the anti-Alzheimer potential of bioactive compounds from Citrus hystrix DC. peel, leaf, and essential oil by network pharmacology

Arisarum vulgare: Bridging Tradition and Science Through Phytochemical Characterization and Exploring Therapeutic Potential via In vitro, In vivo, and In silico Biological Activities

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