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

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Июль 10, 2024

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

Язык: Английский

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Helianthemum oelandicum subsp. incanum and Fumana thymifolia: Characterization of LC-ESI-QTOF-MS profiles and their biological activities based on plant parts and extraction solvents.

Kuwait Journal of Science, Год журнала: 2025, Номер unknown, С. 100378 - 100378

Опубликована: Янв. 1, 2025

Язык: Английский

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Receptors and Natural Products

Опубликована: Янв. 1, 2025

Язык: Английский

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CNEURO-201, an Anti-amyloidogenic Agent and σ1-Receptor Agonist, Improves Cognition in the 3xTg Mouse Model of Alzheimer’s Disease by Multiple Actions in the Pathology

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1301 - 1301

Опубликована: Фев. 3, 2025

The complexity of Alzheimer’s disease (AD) pathophysiology represents a significant challenge in the development effective therapeutic agents for its treatment. CNEURO-201 (CN, also Amylovis-201) is novel pharmaceutical agent with dual activity as an anti-amyloid-β (Aβ) and σ1 receptor agonist. CN exhibits great efficacy at very low doses, delaying cognitive impairment alleviating Aβ load animal models AD. However, functions on other remains related to this pathology remain be investigated. present study sought evaluate effects treatment dosage 0.1 mg kg−1 (p.o) over eight-week period 3xTg-AD mouse model. In silico studies, well biochemical immunofluorescence assays, were conducted brain tissue investigate acetylcholine metabolism, redox system, glial cell activation-related biomarkers regions that are relevant memory. results demonstrated effectively rescues mice by influencing reduce existing plaques but modulating metabolism enzymatic response proteins involved system. Our outcomes reinforced potential treating AD acting multiple pathways altered disease.

Язык: Английский

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Synthesis, in-vitro evaluation and in-silico analysis of new anticholinesterase inhibitors based on sulfinylbis(acylhydrazones) scaffolds

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 141796 - 141796

Опубликована: Фев. 1, 2025

Язык: Английский

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Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review

Plants, Год журнала: 2025, Номер 14(5), С. 827 - 827

Опубликована: Март 6, 2025

Cruciferae family vegetables are remarkably high in phytochemicals such as Indole-3-carbinol (I3C) and Diindolylmethane (DIM), which widely known nutritional supplements. I3C DIM have been studied extensively different types of cancers like breast, prostate, endometrial, colorectal, gallbladder, hepatic, cervical, well other tissues. In this review, we summarized the protective effects against cardiovascular, neurological, reproductive, metabolic, bone, respiratory, liver, immune diseases, infections, drug- radiation-induced toxicities. Experimental evidence suggests that offer protection due to their antioxidant, anti-inflammatory, antiapoptotic, immunomodulatory, xenobiotic properties. Apart from beneficial effects, present review also discusses possible toxicities reported various preclinical investigations. So far, most reports about diseases only studies; emphasizes dire need for large-scale clinical trials on these human diseases. Further, in-depth research is required improve bioavailability two achieve desirable effects. Overall, our may become potential drug candidates combating dreadful

Язык: Английский

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Exploring Alzheimer's Disease Treatment: Established Therapies and Novel Strategies for Future Care

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177520 - 177520

Опубликована: Март 1, 2025

Язык: Английский

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Chemistry and characterization of high value acyclic alcohols in Ocimum africanum Lour. hybrids and their biological potential

Industrial Crops and Products, Год журнала: 2025, Номер 229, С. 120961 - 120961

Опубликована: Апрель 8, 2025

Язык: Английский

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

Heliyon, Год журнала: 2024, Номер 10(13), С. e33496 - e33496

Опубликована: Июнь 26, 2024

Alzheimer's disease (AD) is the most known neurodegenerative disease, and its prevalence predicted to increase significantly. Discovering novel drugs treatments for AD urgently needed. Drugs from natural products have been preferred lately due their high potential low toxicity. Citrus hystrix DC. (kaffir lime; KL) one such herbal plant that found abundantly in Southeast Asia with many biological activities. In this study, of bioactive compounds KL peel, leaf, essential oil as anti-AD agents was explored using network pharmacology. First, were identified KNApSAcK database related literature. Subsequently, targets each corresponding compound determined SEA Search Server Swiss Target Prediction proteins associated OMIM, GenCLiP3, DisGeNET. Furthermore, a protein–protein interaction compound–target constructed identify crucial by employing Cytoscape v3.9.1. The study continued pathway enrichment analysis STRING v1.7.1, molecular docking PyRx SwissDock, dynamics simulation YASARA further confirmation. Our results showed almost all secondary metabolites targeted AD-associated genes, oxypeucedanin citrusoside A showing highest targeting EGFR MAPK14, respectively. These inflammatory oxidative stress pathways, indicating mechanism attenuating clinical manifestation.

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10507 - 10507

Опубликована: Сен. 29, 2024

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

Язык: Английский

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