The beneficial pharmacological effects of Uncaria rhynchophylla in neurodegenerative diseases: focus on alkaloids.

With the intensification of aging population, the prevention or treatment of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, has drawn more and more attention. As a long used traditional Chinese medicine, Uncaria rhynchophylla (Miq.) Jacks., named Gouteng in Chinese, has been reported to have an effective neuroprotective role in neurodegenerative diseases. In this review, the beneficial pharmacological effects and signaling pathways of herbal formulas containing U. rhynchophylla, especially major compounds identified from U. rhynchophylla, such as corynoxine B, corynoxine, rhynchophylline, and isorhynchophylline, in neurodegenerative diseases, were summarized, which not only provide an overview of U. rhynchophylla for the prevention or treatment of neurodegenerative diseases but also give some perspective to the development of new drugs from traditional Chinese medicine.

The effects of whole-body vibration therapy on immune and brain functioning: current insights in the underlying cellular and molecular mechanisms.

Whole-body vibration (WBV) therapy is a way of passive exercise in which subjects are exposed to mild and well-controlled mechanical vibrations through a vibrating platform. For a long time, studies have focused on the effects and applications of WBV to enhance musculoskeletal performance in athletes and patients suffering from musculoskeletal disorders. Recent evidence points toward the positive effect of WBV on the brain and its therapeutic potential in brain disorders. Research being done in the field gradually reveals cellular and molecular mechanisms underlying WBV affecting the body and brain. Particularly, the influence of WBV on immune and brain function is a growing field that warrants an up-to-date and integrated review. Immune function is closely intertwined with brain functioning and plays a significant role in various brain disorders. Dysregulation of the immune response is linked to conditions such as neuroinflammation, neurodegenerative diseases, and mood disorders, highlighting the crucial connection between the immune system and the brain. This review aims to explore the impact of WBV on the cellular and molecular pathways involved in immune and brain functions. Understanding the effects of WBV at a cellular and molecular level will aid in optimizing WBV protocols to improve its therapeutic potential for brain disorders.

Effects of Argon in the Acute Phase of Subarachnoid Hemorrhage in an Endovascular Perforation Model in Rats.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Neuroprotective effects of the noble gas argon have been shown in animal models of ischemia. The aim of this study was to investigate the effects of argon in the immediate early phase of SAH in a rat model. METHODS: A total of 19 male Wistar rats were randomly assigned to three treatment groups. SAH was induced using a endovascular filament perforation model. Cerebral blood flow, mean arterial blood pressure (MAP), and body temperature were measured continuously. Group A received 2 h of ventilation by 50% argon/50% O2 (n = 7) immediately following SAH. Group B underwent a sham operation and was also ventilated by 50% argon/50% O2 (n = 6). Group C underwent SAH and 50% O2/50% N2 ventilation (n = 6). Preoperative and postoperative neurological and behavioral testing were performed. Histology and immunohistochemistry were used to evaluate the extent of brain injury and vasospasm. RESULTS: The cerebral blood flow dropped in both treatment groups after SAH induction (SAH, 63.0 ± 11.6% of baseline; SAH + argon, 80.2 ± 8.2% of baseline). During SAH, MAP increased (135.2 ± 10.5%) compared with baseline values (85.8 ± 26.0 mm Hg) and normalized thereafter. MAP in both groups showed no significant differences (p = 0.3123). Immunohistochemical staining for neuronal nuclear antigen demonstrated a decrease of hippocampal immunoreactivity after SAH in the cornu ammonis region (CA) 1-3 compared with baseline hippocampal immunoreactivity (p = 0.0127). Animals in the argon-ventilated group showed less neuronal loss compared with untreated SAH animals (p < 0.0001). Ionized calcium-binding adaptor molecule 1 staining showed a decreased accumulation after SAH + argon (CA1, 2.57 ± 2.35%; CA2, 1.89 ± 1.89%; CA3, 2.19 ± 1.99%; DG, 2.6 ± 2.24%) compared with untreated SAH animals (CA1, 5.48 ± 2.39%; CA2, 4.85 ± 4.06%; CA3, 4.22 ± 3.01%; dentate gyrus (DG), 3.82 ± 3.23%; p = 0.0007). The neuroscore assessment revealed no treatment benefit after SAH compared with baseline (p = 0.385). CONCLUSION: In the present study, neuroprotective effects of argon occurred early after SAH. Because neurological deterioration was similar in the preadministration and absence of argon, it remains uncertain if neuroprotective effects translate in improved outcome over time.

Insect-derived extracts and peptides in neuroprotection.

Throughout history, various cultures have recognized the significance of insects and have integrated them into traditional medicinal practices. In addition to medicines, insects are garnering attention as a sustainable and nutritious dietary alternative. Although edible insects have long been recognized as food sources in many Asian cultures, recent scientific studies have highlighted their potential therapeutic benefits, particularly in the field of neuroprotection. This review explores insect-derived extracts and peptides, elucidating their neuroprotective potential. This review highlights the potential use of insects as a source of neuroprotective agents. Advancements in neuroprotection may find a key ally in insects as our understanding of the symbiotic relationship between insects and human health becomes more profound.

Systemic administration of blood-derived exosomes induced by remote ischemic post-conditioning, by delivering a specific cluster of miRNAs, ameliorates ischemic damage and neurological function.

MicroRNAs, contained in exosomes or freely circulating in the plasma, might play a pivotal role in the infarct-sparing effect exerted by remote limb ischemic postconditioning (RLIP). The aims of the present study were: (1) To evaluate the effect of pure exosomes isolated from plasma of animals subjected to RLIP systemically administered to ischemic rats; (2) To finely dissect exosomes content in terms of miRNAs; (3) To select those regulatory miRNAs specifically expressed in protective exosomes and to identify molecular pathways involved in their neurobeneficial effects. Circulating exosomes were isolated from blood of animals exposed to RLIP and administered to animals exposed to tMCAO by intracerebroventricular, intraperitoneal or intranasal routes. Exosomal miRNA signature was evaluated by microarray and FISH analysis. Plasmatic exosomes isolated from plasma of RLIP rats attenuated cerebral ischemia reperfusion injury and improved neurological functions until 3 days after ischemia induction. Interestingly, miR-702-3p and miR-423-5p seem to be mainly involved in exosome protective action by modulating NOD1 and NLRP3, two key triggers of neuroinflammation and neuronal death. Collectively, the results of the present work demonstrated that plasma-released exosomes after RLIP may transfer a neuroprotective signal to the brain of ischemic animals, thus representing a potentially translatable therapeutic strategy in stroke.

Integrated elemental analysis supports targeting copper perturbations as a therapeutic strategy in multiple sclerosis.

Multiple sclerosis (MS) is a debilitating affliction of the central nervous system (CNS) that involves demyelination of neuronal axons and neurodegeneration resulting in disability that becomes more pronounced in progressive forms of the disease. The involvement of neurodegeneration in MS underscores the need for effective neuroprotective approaches necessitating identification of new therapeutic targets. Herein, we applied an integrated elemental analysis workflow to human MS-affected spinal cord tissue utilising multiple inductively coupled plasma-mass spectrometry methodologies. These analyses revealed shifts in atomic copper as a notable aspect of disease. Complementary gene expression and biochemical analyses demonstrated that changes in copper levels coincided with altered expression of copper handling genes and downstream functionality of cuproenzymes. Copper-related problems observed in the human MS spinal cord were largely reproduced in the experimental autoimmune encephalomyelitis (EAE) mouse model during the acute phase of disease characterised by axonal demyelination, lesion formation, and motor neuron loss. Treatment of EAE mice with the CNS-permeant copper modulating compound CuII(atsm) resulted in recovery of cuproenzyme function, improved myelination and lesion volume, and neuroprotection. These findings support targeting copper perturbations as a therapeutic strategy for MS with CuII(atsm) showing initial promise.

Forearm access for carotid artery stenting using the dual protection of flow reversal and distal filter: Trans-forearm dual protection technique.

BACKGROUND: Although transfemoral carotid artery stenting (CAS) is widely performed for carotid stenosis, serious or even fatal complications such as embolic and access site complications can still occur. We devised a novel dual protection system with continuous flow reversal to the cephalic vein of the forearm in transradial CAS, referred to as the "trans-forearm dual protection" technique. METHODS: A 75-year-old man with a diagnosis of symptomatic left cervical internal carotid artery (ICA) stenosis underwent CAS using the trans-forearm dual protection technique. RESULTS: A 4F sheath was introduced into the cephalic vein of the right forearm. After an 8F balloon-guiding catheter was navigated into the left common carotid artery (CCA) via right sheathless radial access, a distal filter protection device was advanced into the high cervical ICA. The 8F balloon-guiding catheter was inflated and connected to the 4F sheath with a blood filter interposed. Under the dual protection of flow reversal and distal filter, the CAS procedure was performed. The postprocedural course was uneventful. Diffusion-weighted imaging 2 days after the procedure showed no evidence of ischemic stroke. The patient was discharged home without any complications 1 week after the procedure. Carotid duplex ultrasound performed 9 months after the procedure showed no signs of restenosis. CONCLUSIONS: This method allows for CAS under the dual protection of flow reversal and filter device protection via the trans-forearm access, reducing the risk of embolism and access site complications. Therefore, the trans-forearm dual protection technique can be a useful option for CAS.

Neuroprotective thiourea derivative uncouples mitochondria and exerts weak protonophoric action on lipid membranes.

The isothiourea derivative NT-1505 is known as a neuroprotector and cognition enhancer in animal models of neurodegenerative diseases. Bearing in mind possible relation of the NT-1505-mediated neuroprotection to mitochondrial uncoupling activity, here, we examine NT-1505 effects on mitochondria functioning. At concentrations starting from 10 µM, NT-1505 prevented Ca2+-induced mitochondrial swelling, similar to common uncouplers. Alongside the inhibition of the mitochondrial permeability transition, NT-1505 caused a decrease in mitochondrial membrane potential and an increase in respiration rate in both isolated mammalian mitochondria and cell cultures, which resulted in the reduction of energy-dependent Ca2+ uptake by mitochondria. Based on the oppositely directed effects of bovine serum albumin and palmitate, we suggest the involvement of fatty acids in the NT-1505-mediated mitochondrial uncoupling. In addition, we measured the induction of electrical current across planar bilayer lipid membrane upon the addition of NT-1505 to the bathing solution. Importantly, introduction of the palmitic acid into the lipid bilayer composition led to weak proton selectivity of the NT-1505-mediated BLM current. Thus, the present study revealed an ability of NT-1505 to cause moderate protonophoric uncoupling of mitochondria, which could contribute to the neuroprotective effect of this compound.

Unveiling the shield: Troglitazone's impact on epilepsy-induced nerve injury through ferroptosis inhibition.

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.

Neuroprotective effects of Aframomum pruinosum seed extract against stroke in rat: Role of antioxidant and anti-inflammatory mechanisms.

BACKGROUND: Stroke is a major cause of disability and neurological impairment worldwide. Effective prevention and management strategies are needed to reduce its burden. This study aimed to investigate the therapeutic effect of the seed ethanolic extract of Aframomum pruinosum (EEAP) on stroke and its related motor and cognitive deficits in rats. MATERIALS AND METHODS: Stroke was induced by either middle cerebral artery occlusion (MCAO) or bilateral common carotid artery occlusion (BCCAO). In the MCAO model, rats received EEAP (75, 150, or 300 mg/kg) or N-acetyl-L-cysteine (100 mg/kg) orally for one week before 2 hours of occlusion, followed by reperfusion. Twenty-four hours after ischemia, brain was collected for infarct size using 2, 3, 5 -TriphenylTetrazolium Chloride (TTC) staining, oxidative stress markers and inflammatory cytokines (TNF-α, IL-1ß) measurements. In the BCCAO model, rats underwent occlusion for 30 minutes and received EEAP or quercetin (25 mg/kg) for 7 days post-induction. Behavioral parameters were evaluated at the end of the treatment. Oxidative stress and inflammatory markers were measured in the cerebrum and cerebellum. RESULTS: MCAO caused significant brain infarction, and increased lipid peroxidation, TNF-α and IL-1ß contents. EEAP, rich in nerolidol, prevented these changes in a dose-dependent manner. BCCAO impaired the neurological function, mobility, and muscle strength of rats. It also increased lipid peroxidation and inflammatory cytokines in the cerebellum. EEAP significantly ameliorated these impairments. CONCLUSION: EEAP exerts preventive and curative neuroprotective effects against ischemic stroke and its associated motor impairments at least partially through its antioxidant and anti-inflammatory properties, and its nerolidol content.

Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models.

So far, only a small number of medications are effective in progressive multiple sclerosis (MS). The sphingosine-1-phosphate-receptor (S1PR)-1,5 modulator siponimod, licensed for progressive MS, is acting both on peripheral immune cells and in the central nervous system (CNS). So far it remains elusive, whether those effects are related to the neurotrophin brain derived neurotrophic factor (BDNF). We hypothesized that BDNF in immune cells might be a prerequisite to reduce disease activity in experimental autoimmune encephalomyelitis (EAE) and prevent neurotoxicity. MOG35-55 immunized wild type (WT) and BDNF knock-out (BDNFko) mice were treated with siponimod or vehicle and scored daily in a blinded manner. Immune cell phenotyping was performed via flow cytometry. Immune cell infiltration and demyelination of spinal cord were assessed using immunohistochemistry. In vitro, effects on neurotoxicity and mRNA regulation were investigated using dorsal root ganglion cells incubated with EAE splenocyte supernatant. Siponimod led to a dose-dependent reduction of EAE scores in chronic WT EAE. Using a suboptimal dosage of 0.45 µg/day, siponimod reduced clinical signs of EAE independent of BDNF-expression in immune cells in accordance with reduced infiltration and demyelination. Th and Tc cells in secondary lymphoid organs were dose-dependently reduced, paralleled with an increase of regulatory T cells. In vitro, neuronal viability trended towards a deterioration after incubation with EAE supernatant; siponimod showed a slight rescue effect following treatment of WT splenocytes. Neuronal gene expression for CCL2 and CX3CL1 was elevated after incubation with EAE supernatant, which was reversed after siponimod treatment for WT, but not for BNDFko. Apoptosis markers and alternative death pathways were not affected. Siponimod exerts both anti-inflammatory and neuroprotective effects, partially related to BDNF-expression. This might in part explain effectiveness during progression in MS and could be a target for therapy.

Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.

Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.

The Role of Intravenous Anesthetics for Neuro: Protection or Toxicity?

The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.

Exploring the chemistry, biological effects, and mechanism insights of natural coumaroyltyramine: First report.

Today, pharmaceutical drugs have been shown to have serious side effects, while the bioactive components of botanical plants are proven to be effective in the treatment of several diseases marked by enhanced oxidative stress and mild inflammation, often associated with minimal adverse events. Coumaroyltyramine, designated by various nomenclatures such as paprazine, N-p-trans-coumaroyltyramine, p-coumaroyltyramine and N-p-coumaroyltyramine, could be a promising bioactive ingredient to address health issues thanks to its powerful anti-inflammatory and antioxidant effects. This review represents the first in-depth analysis of coumaroyltyramine, an intriguing phenylpropanoid substance found in many species of plants. In fact, an in-depth examination of coumaroyltyramine's biological characteristics, chemical attributes, and synthesis process has been undertaken. All previous research relating to the discovery, extraction, biosynthesis, and characterization of the biologically and pharmacologically active properties of coumaroyltyramine has been reviewed and taken into consideration in this analysis. All articles published in a peer-reviewed English-language journal were examined between the initial compilations of the appropriate database until February 12, 2024. A variety of phytochemicals revealed that coumaroyltyramine is a neutral amide of hydroxycinnamic acid that tends to concentrate in plants as a reaction against infection caused by pathogens and is extracted from several medicinal herbs such as Cannabis sativa, Solanum melongena, Allium bakeri, Annona cherimola, Polygonatum zanlanscianense, and Lycopersicon esculentum. Thanks to its effectiveness in suppressing the effect of the enzyme α-glucosidase, coumaroltyramine has demonstrated antihyperglycemic activity and could have an impact on diabetes and metabolic disorders. It has considerable anti-inflammatory and antioxidant effects. These results were obtained through biological and pharmacological studies in silico, in vivo, and in vitro. In addition, coumaroyltyramine has demonstrated hypocholesterolemic and neuroprotective benefits, thereby diminishing heart and vascular disease incidence and helping to prevent neurological disorders. Other interesting properties of coumaroltyramine include anticancer, antibacterial, anti-urease, antifungal, antiviral, and antidysmenorrheal activities. Targeted pathways encompass activity at different molecular levels, notably through induction of endoplasmic reticulum stress-dependent apoptosis, arrest of the cell cycle, and inhibition of the growth of cancer cells, survival, and proliferation. Although the findings from in silico, in vivo, and in vitro experiments illustrate coumaroyltyramine's properties and modes of action, further research is needed to fully exploit its therapeutic potential. To improve our understanding of the compound's pharmacodynamic effects and pharmacokinetic routes, large-scale research should first be undertaken. To determine whether coumaroyltyramine is clinically safe and effective, further studies are required in the clinical and toxicological fields. This upcoming research will be crucial to achieving the overall potency of this substance as a natural drug and in terms of its potential synergies with other drugs.

The relevance of BDNF for neuroprotection and neuroplasticity in multiple sclerosis.

Background: Neuroplasticity as a mechanism to overcome central nervous system injury resulting from different neurological diseases has gained increasing attention in recent years. However, deficiency of these repair mechanisms leads to the accumulation of neuronal damage and therefore long-term disability. To date, the mechanisms by which remyelination occurs and why the extent of remyelination differs interindividually between multiple sclerosis patients regardless of the disease course are unclear. A member of the neurotrophins family, the brain-derived neurotrophic factor (BDNF) has received particular attention in this context as it is thought to play a central role in remyelination and thus neuroplasticity, neuroprotection, and memory. Objective: To analyse the current literature regarding BDNF in different areas of multiple sclerosis and to provide an overview of the current state of knowledge in this field. Conclusion: To date, studies assessing the role of BDNF in patients with multiple sclerosis remain inconclusive. However, there is emerging evidence for a beneficial effect of BDNF in multiple sclerosis, as studies reporting positive effects on clinical as well as MRI characteristics outweighed studies assuming detrimental effects of BDNF. Furthermore, studies regarding the Val66Met polymorphism have not conclusively determined whether this is a protective or harmful factor in multiple sclerosis, but again most studies hypothesized a protective effect through modulation of BDNF secretion and anti-inflammatory effects with different effects in healthy controls and patients with multiple sclerosis, possibly due to the pro-inflammatory milieu in patients with multiple sclerosis. Further studies with larger cohorts and longitudinal follow-ups are needed to improve our understanding of the effects of BDNF in the central nervous system, especially in the context of multiple sclerosis.

Reversal of injury-associated retinal ganglion cell gene expression by a phosphodiesterase anchoring disruptor peptide.

Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq). 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.

Emerging Perspectives on Neuroprotection.

Neuroprotection aims to safeguard neurons from damage caused by various factors like stress, potentially leading to the rescue, recovery, or regeneration of the nervous system and its functions [J Clin Neurosci. 2002;9(1):4-8]. Conversely, neuroplasticity refers to the brain's ability to adapt and change throughout life, involving structural and functional alterations in cells and synaptic transmission [Neural Plast. 2014;2014:541870]. Neuroprotection is a broad and multidisciplinary field encompassing various approaches and strategies aimed at preserving and promoting neuronal health. It is a critical area of research in neuroscience and neurology, with the potential to lead to new therapies for a wide range of neurological disorders and conditions. Neuroprotection can take various forms and may involve pharmacological agents, lifestyle modifications, or behavioral interventions. Accordingly, also the perspective and the meaning of neuroprotection differs due to different angles of interpretation. The primary interpretation is from the pharmacological point of view since the most consistent data come from this field. In addition, we will discuss also alternative, yet less considered, perspectives on neuroprotection, focusing on specific neuroprotective targets, interactions with surrounding microglia, different levels of neuroprotective effects, the reversive/adaptative dimension, and its use as anticipatory/prophylactic intervention.

Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation.

Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.

Daidzein's potential in halting neurodegeneration: unveiling mechanistic insights.

Neurological conditions encompassing a wide range of disorders pose significant challenges globally. The complex interactions among signaling pathways and molecular elements play pivotal roles in the initiation and progression of neurodegenerative diseases. Isoflavones have emerged as a promising candidate to fight against neurodegenerative diseases. Daidzein, a 7-hydroxy-3-(4-hydroxyphenyl)-chromen-4-one, belongs to the isoflavone class and exhibits a diverse pharmacological profile. It is found primarily in soybeans and soy products, as well as in some other legumes and herbs. Investigations into daidzein have revealed that it confers neuroprotection by inhibiting oxidative stress, inflammation, and apoptosis, which are key contributors to neuronal damage and degeneration. Activating pathways like PI3K/Akt/mTOR and promoting neurotrophic factors like BDNF by daidzein underscore its potential in supporting neuronal function and combating neurodegeneration. Daidzein's effects on dopamine provide further avenues for intervention in conditions like Parkinson's disease. Additionally, the modulation of inflammatory and NRF-2-antioxidant signaling by daidzein reinforces its neuroprotective role. Moreover, daidzein's interaction with receptors and cellular processes like ER-ß, GPR30, MAO, VEGF, and GnRH highlights its multifaceted effects across multiple pathways involved in neuroprotection and neuronal function. This review article delves into the mechanistic interplay of various mediators in mediating the neuroprotective effects of daidzein. The review article consolidates and analyzes research published over nearly two decades (2005-2024) from various databases, including PubMed, Scopus, ScienceDirect, and Web of Science, to provide a comprehensive understanding of daidzein's effects and mechanisms in neuroprotection.