Heme oxygenase‐1: The roles of both good and evil in neurodegenerative diseases

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 167(3), P. 347 - 361

Published: Sept. 25, 2023

Abstract Heme oxygenase‐1 (HO‐1) is the only way for cells to decompose heme. It can cleave heme produce carbon monoxide (CO), ferrous iron (Fe 2+ ), and biliverdin (BV). BV reduced bilirubin (BR) by reductase(BVR). In previous studies, HO‐1 was considered have protective effects because of its anti‐inflammatory, anti‐apoptosis, antiproliferation functions. However, emerging experimental studies found that metabolites derived from cause increase iin intracellular oxidative stress, mitochondrial damage, death, autophagy. Because particularity, it very meaningful understand exact mechanism. this review, we summarized toxic HO‐1, potential mechanism, role in neurodegenerative diseases related drug research. This knowledge may be beneficial development new therapies crucial therapeutic strategies biomarkers. image

Language: Английский

---

Natural antioxidants that act against Alzheimer’s disease through modulation of the NRF2 pathway: a focus on their molecular mechanisms of action

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: July 3, 2023

Characterized by a complex pathophysiology that includes the intraneuronal formation of neurofibrillary tangles and extracellular deposition β-amyloid plaques, Alzheimer’s disease (AD) is terminal neurodegenerative causes dementia in older adults. Oxidative stress brain considered as one contributing factors to pathogenesis AD, thus, antioxidants have attracted much interest potential therapeutic agents against disorder. Natural are typically characterized low acute chronic toxicity, which facilitates their application. One important molecular target for beneficial effects natural nuclear factor erythroid-derived 2-related 2 (NFE2L2/NRF2). NRF2 key transcription orchestrates cellular antioxidant response through regulating expression oxidative stress-related genes harboring element (ARE) promoters. Indeed, case excessive damage, migrates nucleus binds ARE, activating protector genes. There increasing evidence implicated AD pathology dysfunction altered localization, renders it AD. Thus, this review summarizes most recent (2018-2023) advances on NRF2-modulating activity observed vitro animal models. This information will help elucidate mechanisms governing such phytochemicals highlight common diseases,

Language: Английский

---

Rutin prevents pyroptosis and M1 microglia via Nrf2/Mac-1/caspase-1-mediated inflammasome axis to improve POCD

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 127, P. 111290 - 111290

Published: Dec. 7, 2023

Language: Английский

---

Neurotrophic Natural Products

Fortschritte der Chemie Organischer Naturstoffe/Fortschritte der Chemie organischer Naturstoffe/Progress in the chemistry of organic natural products, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 473

Published: Jan. 1, 2024

Language: Английский

---

Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer’s Disease

Current Topics in Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 24(19), P. 1683 - 1698

Published: April 27, 2024

: Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as 2023. It characterized by cognitive dysfunction and an inability to perform daily activities. The progression AD associated with accumulation amyloid beta (Aβ), formation neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, endoplasmic reticulum stress. Presently, various phytomedicines their bioactive compounds have been identified for neuroprotective effects in reducing alleviating mitigating Aβ acetylcholinesterase enzymes hippocampus cerebral cortex regions brain. However, despite demonstrating promising anti-Alzheimer's effects, clinical utilization phytoconstituents remains limited scope. key factor contributing this limitation challenges inherent traditional drug delivery systems, which impede effectiveness efficiency. These difficulties encompass insufficient targeting, restricted solubility stability, brief duration action, a lack control over release. Consequently, these constraints result diminished bioavailability permeability across blood-brain barrier (BBB). In response challenges, novel systems (NDDS) founded on nanoformulations emerged hopeful strategy augment BBB poor solubility. Among nanoemulsion (NE) extensively investigated potential targeting AD. NE offers several advantages, such ease preparation, high loading, stability. Due nanosize droplets, also improves gut leading enhanced systemic circulation Various studies reported testing NE-based bioactives different animal species, including transgenic, Wistar, Sprague-Dawley (SD) rats, well mice. transgenic mice are commonly employed research analyze Aβ. review, aspects role phytoconstituents, conventional delivery, need NDDS, particularly NE, discussed. involving phytoconstituent-based treatment

Language: Английский

---

Rosavin thwarts amyloid-β-induced macromolecular damages and neurotoxicity, exhibiting anti-Alzheimer’s disease activity in Wister rat model

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 32(2), P. 1461 - 1474

Published: Sept. 27, 2023

Language: Английский

---

The Overview of Drugs Used in Alzheimer’s Disease and Their Molecular Targets

Published: Jan. 1, 2023

Alzheimer's disease (AD) is a progressive condition in which degeneration of neuronal cells observed the brain. There are many drugs approved by FDA for treatment AD and it includes galantamine, donepezil, rivastigmine, memantine, aducanumab. Among available drugs, rivastigmine acetylcholinesterase inhibitor they enhance cholinergic neurons Another drug memantine N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist. It prevents excitotoxicity cell apoptosis. Similarly, aducanumab recently attenuates accumulation amyloid beta protein. synthetic herbal bioactives that have been reported against AD. Some possess low bioavailability BBB permeability. Due to this, show less therapeutic action at target site Such moieties can be incorporated into advanced delivery system their blood–brain barrier (BBB) The chapter describes an overview various strategies as well nanomedicines developed so treat

Language: Английский

---

Integrating serum pharmacochemistry and network pharmacology to reveal the active constituents and mechanism of Corydalis Rhizoma in treating Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Nov. 22, 2023

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients treating AD has attracted much attention. Corydalis rhizome (CR) medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used AD. However, no systematic study been conducted to explore the anti-AD efficacy of CR, as well its active compounds and mechanisms action. present aimed clarify CR's constituents pharmacological in A D-galactose & scopolamine hydrobromide-induced mouse model was CR administered orally. prototypical alkaloid were identified serum. core components, key targets, possible action these alkaloids revealed through network pharmacology. Molecular docking target performed. Finally, mechanism validated by lipopolysaccharide (LPS)-induced activation BV2 microglia. results showed improved anxiety-like behavior, spatial non-spatial recognition, memory capacity mice. It also achieved synergistic treatment modulating neurotransmitter levels, anti-neuroinflammation, anti-oxidative stress. enhance protoberberine-type alkaloids. may induce polarization LPS-activated microglia from phenotype M1 M2. This partially IL-6/JAK2/STAT3 signaling pathway, could treats anti-inflammation. provided theoretical experimental basis clinical application provides information aids secondary development, precise use CR.

Language: Английский

---

2‐Oxoquinoline‐based‐thiosemicarbazones as multitargeting neurotherapeutics against Alzheimer's disease: In vitro and in silico studies of MAO and ChE inhibitors

Archiv der Pharmazie, Journal Year: 2023, Volume and Issue: 356(11)

Published: Sept. 17, 2023

Alzheimer's disease (AD) presents a multifactorial neurological disorder with multiple enzyme involvement in its onset. Conventional monotherapies fall short providing long-term relief, necessitating the exploration of alternative multitargeting approaches to address complexity AD. Therefore, design, synthesis, and vitro silico evaluation 2-oxoquinoline-based thiosemicarbazones 9a-r as multipotent analogs, able simultaneously inhibit cholinesterase (ChE) monoamine oxidase (MAO) enzymes for potential treatment AD, are reported. In experimental MAO ChE inhibition, all tested compounds demonstrated remarkable potency exhibiting nonselective inhibition both MAO-A MAO-B, selective acetylcholinesterase (AChE) over butyrylcholinesterase (BChE), 9d, 9j, 9m evolving lead MAO-A, AChE, displaying IC50 values 0.35 ± 0.92, 0.50 0.02, 0.25 0.13 μM, respectively. Moreover, kinetic studies revealed that inhibited three through competitive mode inhibition. Furthermore, molecular docking most active several crucial interactions, particularly hydrogen bonding interactions. These interactions were observed between nitrogen sulfur atoms thiosemicarbazone oxygen quinoline ring various amino acids, suggesting strong these enzymes.

Language: Английский

---

Natural Medicines (Phytoconstituents) and Probiotics as the Future of Alzheimer’s Disease

Published: Jan. 1, 2024

Language: Английский

---