Promising thiazolidinedione-thiazole based multi-target and neuroprotective hybrids for Alzheimer’s disease: Design, synthesis, in-vitro, in-vivo and in-silico studies

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 287, С. 117327 - 117327

Опубликована: Фев. 3, 2025

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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Inhibition of Inflammatory Regulators for Chronic Obstructive Pulmonary Disease (COPD) Treatment from Indonesian Medicinal Plants: A Systematic Review

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 262 - 262

Опубликована: Апрель 8, 2025

A characteristic of Chronic Obstructive Pulmonary Disease (COPD) is the inflammation respiratory pathway. Inflammatory regulators affected in COPD include cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), interleukin (IL-1β), and interleukin-6 (IL-6). Therefore, this systematic review aimed to investigate biological activity Indonesian medicinal plants as anti-inflammation through vitro, silico, vivo studies. digital search was conducted using Scopus, Google Scholar, PubMed online databases find relevant articles by applying specific keywords related subject interest. The results showed 18 studies that reported five proven inhibit regulation. were sambiloto (Andrographis paniculata), legetan warak (Adenostemma lavenia), kersen (Muntingia calabura), babadotan (Ageratum conyzoides), sembung rambat (Mikania micrantha Kunth). In vitro studies, A. paniculata, lavenia, M. calabura can suppress levels pro-inflammatory cytokines, such TNF-α, IL-1β, IL-6, LPS-stimulated RAW 264.7 cells. silico compounds have strong binding bind inflammatory receptors are andrographiside contained paniculata; ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid lavenia; 7-Hydroxyflavone calabura; 22,23-Dihydrospinasterol conyzoides. extracts calabura, conyzoides, reduce lung tissue animal models (hamsters, mice, rats). This might help develop treatment build scientifically natural products from for future investigations.

Язык: Английский

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Identification of novel small molecule chaperone activators for neurodegenerative disease treatment

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 187, С. 118049 - 118049

Опубликована: Апрель 15, 2025

Язык: Английский

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The Coast’s Natural Resources Offer a Promising in Silico Approach for Alzheimer’s Disease Medication

IOP Conference Series Earth and Environmental Science, Год журнала: 2025, Номер 1473(1), С. 012059 - 012059

Опубликована: Март 1, 2025

Abstract Alzheimer’s disease (AD) is becoming a significant health issue on an ecumenical scale, with substantial financial and impact families societies. It characterized mostly by complete dementia, which includes memory loss, cognitive impairment, executive dysfunction, pearsonality alteration, behavior changes. Furthermore, the majority of patients experience symptoms mental disturbance. There are presently no treatments that can prevent or cure AD; however, medicine provide temporary respite for these symptoms. Several studies have shown correlation between development AD, disturbances in lipid metabolism, neuroinflammation. We used silico strategy to investigate bioactive flavonoids coastal prickly pear cactus cladode. This cladode has four active compounds bind well interact inhibitor sites cyclooxygenase-2 (COX-2), soluble epoxide hydrolase (sEH), cytosolic 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS1). The study suggests cladode, contains flavonoids, may hold promise as potential natural AD medication.

Язык: Английский

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Multifaceted Biological Activities of Culinary Herb and Spice Extracts: In Vitro and In Silico Simulation Insights into Inflammation-Related Targets

Foods, Год журнала: 2025, Номер 14(9), С. 1456 - 1456

Опубликована: Апрель 23, 2025

Culinary herbs and spices are valued worldwide for their flavor, aroma, medicinal benefits. They encompass diverse bioactive metabolites, such as polyphenols terpenoids, which contribute to plant defense offer anticarcinogenic, anti-inflammatory, antioxidant, cognitive-enhancing effects. This study aimed establish the volatile fingerprint of culinary (lemon verbena, chives, basil, sage, coriander, parsley) (curcuma, nutmeg, cumin, black pepper, Jamaica juniper berry) using headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME/GC-MS). The predominant organic metabolites (VOMs) identified were subjected in silico molecular docking simulations anti-Alzheimer’s (e.g., acetylcholinesterase (AChE), butyrylcholinesterase (BChE)), antioxidants monoamine oxidase B (MAO-B), inducible nitric oxide synthase (iNOS)), anti-inflammatory receptors 5-lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2)). herb spice extracts also vitro assays evaluate potential antioxidant (DPPH, ABTS, ORAC) (% protein denaturation) agents. A total 121 VOMs spices, chemical families being monoterpenoids (48.3%), sesquiterpenoids (14.0%), esters (11.9%), carbonyl compounds (8.8%). In revealed that cuminaldehyde, β-caryophyllene, γ-curcumene, germacrene D, τ-cadinol exhibited strongest inhibitory activities against selected receptors. Among extracts, pepper showed highest activities, while lemon verbena lowest ones. These findings highlight promising studied modulation inflammatory processes related Alzheimer’s disease. However, further investigations, particularly clinical studies, recommended validate these results explore therapeutic applications.

Язык: Английский

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Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication

Reviews in the Neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Abstract Effective communication between different cell types is essential for brain health, and dysregulation of this process leads to neuropathologies. Brain glial cells, including microglia astrocytes, orchestrate immune defense neuroimmune responses under pathological conditions during which interglial indispensable. Our appreciation the complexity these processes rapidly increasing due recent advances in molecular biology techniques, have identified numerous phenotypic states both astrocytes. This review focuses on microglia-to-astrocyte facilitated by secreted modulators. The combinations interleukin (IL)-1α, tumor necrosis factor (TNF), plus complement component C1q as well IL-1β TNF are already well-established microglia-derived stimuli that induce reactive phenotypes However, given large number inflammatory mediators distinct functional recognized it can be hypothesized many more intercellular signaling molecules exist. identifies following group cytokines gliotransmitters that, while not established yet, known released elicit astrocytes: IL-10, IL-12, IL-18, transforming growth (TGF)-β, interferon (IFN)-γ, C–C motif chemokine ligand (CCL)5, adenosine triphosphate (ATP), l -glutamate, prostaglandin E2 (PGE2). mechanisms engaged reveals complex, partially overlapping pathways implicated Additionally, lack human-specific studies a significant knowledge gap. Further research warranted, could discover novel signaling-targeted therapies diverse neurological disorders.

Язык: Английский

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Acyclic sesquiterpenes nerolidol and farnesol: mechanistic insights into their neuroprotective potential

Pharmacological Reports, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Язык: Английский

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A Fast-Binding, Functionally Reversible, COX-2 Radiotracer for CNS PET Imaging

ACS Central Science, Год журнала: 2024, Номер 10(5), С. 1105 - 1114

Опубликована: Апрель 25, 2024

Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In central nervous system (CNS), COX-2 implicated neurodegenerative psychiatric disorders as potential therapeutic target biomarker. However, clinical studies with have yielded inconsistent results, partly due to limited mechanistic understanding of how activity relates CNS pathology. Therefore, developing positron emission tomography (PET) radiotracers for human neuroimaging interest. This study introduces [11C]BRD1158, which potent uniquely fast-binding, selective PET radiotracer. [11C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, free fraction brain. Evaluated through vivo rodent models overexpression, demonstrated high brain uptake, target-engagement, functional reversibility, excellent specific binding, advantageous imaging applications. Lastly, post-mortem samples from Huntington's disease (HD) patients preclinical HD mouse showed levels were elevated specifically disease-affected regions, primarily increased expression microglia. These findings indicate holds promise novel marker onset progression, one many applications PET.

Язык: Английский

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Synergistic integration of deep learning with protein docking in cardiovascular disease treatment strategies

IUBMB Life, Год журнала: 2024, Номер 76(9), С. 666 - 696

Опубликована: Май 15, 2024

Abstract This research delves into the exploration of potential tocopherol‐based nanoemulsion as a therapeutic agent for cardiovascular diseases (CVD) through an in‐depth molecular docking analysis. The study focuses on elucidating interactions between tocopherol and seven key proteins (1O8a, 4YAY, 4DLI, 1HW9, 2YCW, 1BO9 1CX2) that play pivotal roles in CVD development. Through rigorous silico investigations, assessment was conducted binding affinities, inhibitory potentials interaction patterns with these target proteins. findings revealed significant interactions, particularly displaying robust energy −6.39 kcal/mol promising Ki value 20.84 μM. Notable were also observed 2YCW 1CX2, further indicating tocopherol's relevance. In contrast, no 1BO9. Furthermore, examination common residues 4YAY bound to carried out, highlighting intermolecular hydrophobic bonds contribute interaction's stability. Tocopherol complies pharmacokinetics (Lipinski's Veber's) rules oral bioavailability proves safety non‐toxic non‐carcinogenic. Thus, deep learning‐based protein language models ESM1‐b ProtT5 leveraged input encodings predict sites tocopherol. Hence, highly accurate predictions critical protein–ligand achieved. not only advances understanding but highlights learning's immense biology drug discovery. It underscores promise disease management candidate, shedding light its compatibility biomolecule‐like characteristics.

Язык: Английский

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