Neuroprotective Properties Research Articles

Lutein and the Underlying Neuroprotective Promise against Neurodegenerative Diseases.

Alzheimer's disease (AD) and Parkinson's diseases (PD) are the two most common progressive neurodegenerative diseases with limited knowledge on their cause and, presently, have no cure. There is an existence of multiple treatment methods that target only the symptoms temporarily and do not stop the progression or prevent the onset of disease. Neurodegeneration is primarily attributed to the natural process of aging and the deleterious effects of heightened oxidative stress within the brain, whether via direct or indirect mechanisms. Emerging evidence suggests that certain nutritional aspects play a crucial role in the prevention and management of neurodegenerative diseases. Lutein, a dietary carotenoid, has been studied for its antioxidant properties for more than a decade with several applications against age-related macular degeneration. It is high antioxidant potential and selective accumulation in the brain makes it a versatile compound for combatting various neurodegenerative diseases. In this review, the studies exhibiting neuroprotective properties of lutein against neurodegenerative conditions, more specifically AD and PD in various model systems as well as clinical observations have been reviewed. Accordingly, the concerns associated with lutein absorption and potential strategies to improve its bioavailability have been discussed.

Myricetin Amorphous Solid Dispersions-Antineurodegenerative Potential.

Our research aimed to develop an amorphous solid dispersion (ASD) of myricetin (MYR) with Polyvinylpyrrolidone K30 (PVP30) to enhance its solubility, dissolution rate, antioxidant, and neuroprotective properties. Employing a combination of solvent evaporation and freeze drying, we successfully formed MYR ASDs. XRPD analysis confirmed complete amorphization in 1:8 and 1:9 MYR-PVP weight ratios. DSC thermograms exhibited a single glass transition (Tg), indicating full miscibility. FT-IR results and molecular modeling confirmed hydrogen bonds stabilizing MYR's amorphous state. HPLC analysis indicated the absence of degradation products, ensuring safe MYR delivery systems. Solubility, dissolution rate (pH 1.2 and 6.8), antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays), and in vitro neuroprotective activities (inhibition of cholinesterases: AChE and BChE) were significantly improved compared to the pure compound. Molecular docking studies revealed that MYR had made several hydrogen, hydrophobic, and π-π stacking interactions, which could explain the compound's potency to inhibit AChE and BChE. MYR-PVP 1:9 w/w ASD has the best solubility, antioxidant, and neuroprotective activity. Stability studies confirmed the physical stability of MYR-PVP 1:9 w/w ASD immediately after dissolution and for two months under ambient conditions. Our study showed that the obtained ASDs are promising systems for the delivery of MYR with the potential for use in alleviating the symptoms of neurodegenerative diseases.

Exploring the Possible Role of Cannabinoids in Managing Post-Cardiac Surgery Complications: A Narrative Review of Preclinical Evidence and a Call for Future Research Directions.

Open-heart surgery with cardiopulmonary bypass (CPB) often leads to complications including pain, systemic inflammation, and organ damage. Traditionally managed with opioids, these pain relief methods bring potential long-term risks, prompting the exploration of alternative treatments. The legalization of cannabis in various regions has reignited interest in cannabinoids, such as CBD, known for their anti-inflammatory, analgesic, and neuroprotective properties. Historical and ongoing research acknowledges the endocannabinoid system's crucial role in managing physiological processes, suggesting cannabinoids could offer therapeutic benefits in post-surgical recovery. Specifically, CBD has shown promise in managing pain, moderating immune responses, and mitigating ischemia/reperfusion injury, underscoring its potential in postoperative care. However, the translation of these findings into clinical practice faces challenges, highlighting the need for extensive research to establish effective, safe cannabinoid-based therapies for patients undergoing open-heart surgery. This narrative review advocates for a balanced approach, considering both the therapeutic potential of cannabinoids and the complexities of their integration into clinical settings.

Former smoking, but not active smoking, is associated with delirium in postoperative ICU patients: a matched case-control study.

To examine the relationship between current and former smoking and the occurrence of delirium in surgical Intensive Care Unit (ICU) patients. We conducted a single center, case-control study involving 244 delirious and 251 non-delirious patients that were admitted to our ICU between 2018 and 2022. Using propensity score analysis, we obtained 115 pairs of delirious and non-delirious patients matched for age and Simplified Acute Physiology Score II (SAPS II). Both groups of patients were further stratified into non-smokers, active smokers and former smokers, and logistic regression was performed to further investigate potential confounders. Our study revealed a significant association between former smoking and the incidence of delirium in ICU patients, both in unmatched (adjusted odds ratio (OR): 1.82, 95% confidence interval (CI): 1.17-2.83) and matched cohorts (OR: 3.0, CI: 1.53-5.89). Active smoking did not demonstrate a significant difference in delirium incidence compared to non-smokers (unmatched OR = 0.98, CI: 0.62-1.53, matched OR = 1.05, CI: 0.55-2.0). Logistic regression analysis of the matched group confirmed former smoking as an independent risk factor for delirium, irrespective of other variables like surgical history (p = 0.010). Notably, also respiratory and vascular surgeries were associated with increased odds of delirium (respiratory: OR: 4.13, CI: 1.73-9.83; vascular: OR: 2.18, CI: 1.03-4.59). Medication analysis showed that while Ketamine and Midazolam usage did not significantly correlate with delirium, Morphine use was linked to a decreased likelihood (OR: 0.27, 95% CI: 0.13-0.55). Nicotine's complex neuropharmacological impact on the brain is still not fully understood, especially its short-term and long-term implications for critically ill patients. Although our retrospective study cannot establish causality, our findings suggest that smoking may induce structural changes in the brain, potentially heightening the risk of postoperative delirium. Intriguingly, this effect seems to be obscured in active smokers, potentially due to the recognized neuroprotective properties of nicotine. Our results motivate future prospective studies, the results of which hold the potential to substantially impact risk assessment procedures for surgeries.

Tanshinone IIA Against Cerebral Ischemic Stroke and Ischemia-Reperfusion Injury: A Review of the Current Documents.

Stroke is a well-known neurological disorder that carries significant morbidity and mortality rates worldwide. Cerebral Ischemic Stroke (CIS), the most common subtype of stroke, occurs when thrombosis or emboli form elsewhere in the body and travel to the brain, leading to reduced blood perfusion. Cerebral Ischemia/Reperfusion Injury (CIRI) is a common complication of CIS and arises when blood flow is rapidly restored to the brain tissue after a period of ischemia. The therapeutic approaches currently recognized for CIS, such as thrombolysis and thrombectomy, have notable side effects that limit their clinical application. Recently, there has been growing interest among researchers in exploring the potential of herbal agents for treating various disorders and malignancies. One such herbal agent with medicinal applications is tanshinone IIA, an active diterpene quinone extracted from Salvia miltiorrhiza Bunge. Tanshinone IIA has shown several pharmacological benefits, including anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective properties. Multiple studies have indicated the protective role of tanshinone IIA in CIS and CIRI. This literature review aims to summarize the current findings regarding the molecular mechanisms through which this herbal compound improves CIS and CIRI.

Medicinal herbal remedies in neurodegenerative diseases: an update on antioxidant potential.

It has been widely documented that medicinal herbal remedies are effective, have fewer side effects than conventional medicine, and have a synergistic effect on health collaborations in the fight against complicated diseases. Traditional treatments for neurological problems in ancient times sometimes involved the use of herbal remedies and conventional methods from East Asian countries including India, Japan, China, and Korea. We collected and reviewed studies on plant-derived neuroprotective drugs and tested them in neurotoxic models. Basic research, preclinical and clinical transgene research can benefit from in silico, in vitro, and in vivo investigations. Research, summaries of the extracts, fractions, and herbal ingredients were compiled from popular scientific databases, which were then examined according to origin and bioactivity. Given the complex and varied causes of neurodegeneration, it may be beneficial to focus on multiple mechanisms of action and a neuroprotection approach. This approach aims to prevent cell death and restore function to damaged neurons, offering promising strategies for preventing and treating neurodegenerative diseases. Neurodegenerative illnesses can potentially be treated with natural compounds that have been identified as neuroprotective agents. To gain deeper insights into the neuropharmacological mechanisms underlying the neuroprotective and therapeutic properties of naturally occurring antioxidant phytochemical compounds in diverse neurodegenerative diseases, this study aims to comprehensively review such compounds, focusing on their modulation of apoptotic markers such as caspase, Bax, Bcl-2, and proinflammatory markers. In addition, we delve into a range of efficacies of antioxidant phytochemical compounds as neuroprotective agents in animal models. They reduce the oxidative stress of the brain and have been shown to have anti-apoptotic effects. Many researches have demonstrated that plant extracts or bioactive compounds can fight neurodegenerative disorders. Herbal medications may offer neurodegenerative disease patients' new treatments. This may be a cheaper and more culturally appropriate alternative to standard drugs for millions of people with age-related NDDs.

An in vitro analysis of an innovative standardized phospholipid carrier-based Melissa officinalis L. extract as a potential neuromodulator for emotional distress and related conditions.

Background: Melissa officinalis L. (MO), commonly known as lemon balm, a member of the mint family, is considered a calming herb. In various traditional medicines, it has been utilized to reduce stress and anxiety and promote sleep. A growing body of clinical evidence suggests that MO leaf extract supplementation possesses considerable neuropharmacological properties. However, its possible mechanism of action largely remains unknown. Objective: In the present in vitro studies, we comparatively investigated the central nervous system (CNS)-calming and antioxidative stress properties of an innovative standardized phospholipid carrier-based (Phytosome™) MO extract (Relissa™) vs. an unformulated dry MO extract. Methods: The neuropharmacological effect of the extract was studied in the anti-depressant enzymes γ-aminobutyrate transaminase (GABA-T) and monoamine oxidase A (MAO-A) assays and SH-SY5Y cells brain-derived neurotrophic factor (BDNF) expression assay. The neuroprotective effect of the extract against oxidative stress was assessed in SH-SY5Y cell-based (H2O2-exposed) Total Antioxidant Status (TAS) and Total Reactive Oxygen Species (ROS) assays. The cytotoxic effect of the extract was evaluated using MTT and LDH assays. The extract antioxidant effect was also evaluated in cell-free chemical tests, including TEAC-ABTS, DPPH, Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Antioxidant Capacity (ORAC), and Hydroxyl Radical Antioxidant Capacity (HORAC) assays. Results: Relissa™ exhibited high GABA-T inhibitory activity, IC50 (mg/mL) = 0.064 vs. unformulated dry MO extract, IC50 (mg/mL) = 0.27. Similar inhibitory effects were also observed for MAO-A. Relissa™ demonstrated an improved neuroprotective antioxidant effect on SH-SY5Y cells against H2O2-induced oxidative stress. Compared to unformulated dry MO extract, Relissa™ exerted high protective effect on H2O2-exposed SH-SY5Y cells, leading to higher cells BDNF expression levels. Moreover, cell-free chemical tests, including TEAC-ABTS, DPPH radical scavenging, FRAP, ORAC, and HORAC assays, validated the improved antioxidant effect of Relissa™ vs. unformulated dry MO extract. Conclusion: The results of the present study support the neuromodulating and neuroprotective properties of Relissa™, and its supplementation may help in the amelioration of emotional distress and related conditions.

Deciphering the multi-functional role of Indian propolis for the management of Alzheimer's disease by integrating LC-MS/MS, network pharmacology, molecular docking, and in-vitro studies.

The conventional one-drug-one-disease theory has lost its sheen in multigenic diseases such as Alzheimer's disease (AD). Propolis, a honeybee-derived product has ethnopharmacological evidence of antioxidant, anti-inflammatory, antimicrobial and neuroprotective properties. However, the chemical composition is complex and highly variable geographically. So, to leverage the potential of propolis as an effective treatment modality, it is essential to understand the role of each phytochemical in the AD pathophysiology. Therefore, the present study was aimed at investigating the anti-Alzheimer effect of bioactive in Indian propolis (IP) by combining LC-MS/MS fingerprinting, with network-based analysis and experimental validation. First, phytoconstituents in IP extract were identified using an in-house LC-MS/MS method. The drug likeness and toxicity were assessed, followed by identification of AD targets. The constituent-target-gene network was then constructed along with protein-protein interactions, gene pathway, ontology, and enrichment analysis. LC-MS/MS analysis identified 16 known metabolites with druggable properties except for luteolin-5-methyl ether. The network pharmacology-based analysis revealed that the hit propolis constituents were majorly flavonoids, whereas the main AD-associated targets were MAOB, ESR1, BACE1, AChE, CDK5, GSK3β, and PTGS2. A total of 18 gene pathways were identified to be associated, with the pathways related to AD among the topmost enriched. Molecular docking analysis against top AD targets resulted in suitable binding interactions at the active site of target proteins. Further, the protective role of IP in AD was confirmed with cell-line studies on PC-12, in situ AChE inhibition, and antioxidant assays.

Mild hypothermia reduces lipopolysaccharide-induced microglial activation via down-regulation of Tent5c

Microglial activation is a critical factor in the pathogenesis and progression of neuroinflammatory diseases. Mild hypothermia, known for its neuroprotective properties, has been shown to alleviate microglial activation. In this study, we explore the differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) in BV-2 microglial cells under different conditions: normal temperature (CN), mild hypothermia (YT), normal temperature with lipopolysaccharide (LPS), and mild hypothermia with LPS (LPS + YT). Venn analysis revealed 119 DE mRNAs that were down-regulated in the LPS + YT vs LPS comparison but up-regulated in the CN vs LPS comparison, primarily enriched in Gene Ontology terms related to immune and inflammatory responses. Furthermore, through Venn analysis of YT vs CN and LPS + YT vs LPS comparisons, we identified 178 DE mRNAs and 432 DE lncRNAs. Among these transcripts, we validated the expression of Tent5c at the protein and mRNA levels. Additionally, siRNA-knockdown of Tent5c attenuated the expression of pro-inflammatory genes (TNF-α, IL-1β, Agrn, and Fpr2), cellular morphological changes, NLRP3 and p-P65 protein levels, immunofluorescence staining of p-P65 and number of cells with ASC-speck induced by LPS. Furthermore, Tent5c overexpression further potentiated the aforementioned indicators in the context of mild hypothermia with LPS treatment. Collectively, our findings highlight the significant role of Tent5c down-regulation in mediating the anti-inflammatory effects of mild hypothermia.

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model.

RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model. We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model. The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ-carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK-NTRK2 complex showed more stable and stronger interactions as compared to the RNYK-NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318. The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

Purinergic Astrocyte Signaling Driven by TNF-α After Cannabidiol Administration Restores Normal Synaptic Remodeling Following Traumatic Brain Injury

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.

Neuroprotective properties of plant extract green-formulated silver nanoparticles on the contusive model of spinal cord injury in rats

Silver nanoparticles (Ag NPs) are highly sought-after metal nanoparticles globally due to their distinctive electronic and optical characteristics, as well as their biological properties. These attributes stem from the synchronized movements of conduction electrons, referred to as surface plasmon resonance. Currently, numerous bio-medical characteristics of biosynthesized Ag nanoparticles have been thoroughly documented, including their anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Nevertheless, there have been no reports regarding the neuroprotective efficacy of these nanoparticles against cytotoxic agents. It appears that the defensive capabilities of the NPs formulated by green methods have been disregarded thus far. We recently did research to assess the neuroprotective effects of a combination of Tribulus terrestris and green-mediated silver nanoparticles on a contusive spinal cord injury model in animals. The silver nanoparticles underwent comprehensive characterization through UV–Vis, FE-SEM, FT-IR, and TEM analyses. In the in vivo phase of the research, a total of forty rats were categorized into three groups: untreated, normal, and silver nanoparticles (50 µg/kg) groups. The post-injury lesions were analyzed using H&E staining. To evaluate the restoration of neural conduction, somatosensory evoked potential testing was conducted. The presence of astrogliosis was determined by evaluating the expression of GFAP. The rats' behavioral outcomes were assessed using the BBB score every week. The utilization of silver nanoparticles demonstrated neuroprotective properties and resulted in enhancements in spinal cord injury. The results of the sensory assessments indicated a notable rise in the Basso, Beattie, and Bresnahan scales, along with a marked decline in delayed reactions, among the subjects who received treatment with silver nanoparticles. The most substantial decrease in GFAP levels was noted in the group that was administered silver nanoparticles. Furthermore, there was a substantial decrease in the size of the cavity regions, while the quantity of ventral motor neurons experienced a significant rise within the silver nanoparticles group. The electromyography (EMG) results demonstrated a remarkable enhancement in the hindlimbs of the subjects who received treatment with silver nanoparticles (50 µg/kg).

Green synthesis, chemical characterization, and protective potentials of silver nanoparticles on the development of cerebrovascular diseases in rat cerebral ischemia reperfusion injury

Thrombolysis or mechanical recanalization are two methods that can be used to restore blood flow after an ischemic stroke. However, it is important to note that in certain situations, reperfusion can actually exacerbate the initial damage caused by ischemia, leading to a condition known as “cerebral reperfusion injury.” This injury involves several pathological processes, including the infiltration of leukocytes, activation of platelets and complement, postischemic hyperperfusion, and disruption of the blood–brain barrier. The main objective of research conducted globally is to create a novel therapeutic medication for stroke. In light of the nano revolution, it is imperative to merge nanoscience and medicine. Knowledge acquired from nature has paved the path for the development of biogenic technologies, facilitating the production of cutting-edge nanomaterials. We have recently conducted a study to evaluate the neuroprotective properties of a blend of Mellisa officinalis leaf extract and green-mediated silver nanoparticles on the development of cerebrovascular diseases in rat cerebral ischemia reperfusion injury. The silver nanoparticles were thoroughly examined using UV–Vis, FE-SEM, and EDX analyses to ensure comprehensive characterization. The Ag NPs were observed to have various polymorphic shapes and were found to be aggregated. Also, the particles average size was measured by ImageJ software and it is about 29.15 nm. The UV–Vis measurements showed that the spectra displayed the highest absorption at around 432 nm. The stroke occurred as a result of the occlusion of the middle cerebral artery for 1.5 h, followed by reperfusion for 2 days. Before the ischemia reperfusion, the rats received an intravenous injection of AgNPs at doses of 40, 80 and 160 µg/kg once daily for a consecutive period of 3 days. The evaluation of the cell damage index involved assessing various factors such as immunoglobulin G (IgG) extravasation into the cerebral parenchyma, lactate dehydrogenase efficacy, serum MDA level, infarct volume, and learning and memory function. The results of the study showed that pretreatment with AgNPs had a protective effect on stroke in animals. Moreover, AgNPs effectively alleviated the memory and learning impairments caused by stroke. Additionally, AgNPs significantly reduced infarct volume, IgG extravasation, serum MDA level, and lactate dehydrogenase efficacy.

Agmatine mitigates behavioral abnormalities and neurochemical dysregulation associated with 3-Nitropropionic acid-induced Huntington's disease in rats

Huntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties. The present study was designed to examine the influence of agmatine on the behavioral, biochemical, and molecular aspects of HD in an animal model. A mitochondrial toxin, 3-nitro propionic acid (3-NP), was used to induce HD phenotype and similar symptoms such as motor incoordination, memory impairment, neuro-inflammation, and depressive-like behavior in rats. Rats were pre-treated with 3-NP (10 mg/kg, i.p.) on days 1, 3, 5, 7, and 9 and then continued on agmatine treatment (5 – 20 µg/rat, i.c.v.) from day-8 to day-27 of the treatment protocol. 3-NP-induced cognitive impairment was associated with declined in agmatine levels within prefrontal cortex, striatum, and hippocampus. Further, the 3-NP-treated rats showed an increase in IL-6 and TNF-α and a reduction in BDNF immunocontent within these brain areas. Agmatine treatment not only improved the 3-NP-induced motor incoordination, depression-like behavior, rota-rod performance, and learning and memory impairment but also normalized the GABA/glutamate, BDNF, IL-6, and TNF-α levels in discrete brain areas. Similarly, various agmatine modulators, which increase the endogenous agmatine levels in the brain, such as L-arginine (biosynthetic precursor), aminoguanidine (diamine oxidase inhibitor), and arcaine (agmatinase inhibitor) also demonstrated similar effects exhibiting the importance of endogenous agmatinergic pathway in the pathogenesis of 3-NP-induced HD like symptoms. The present study proposed the possible role of agmatine in the pathogenesis and treatment of HD associated motor incoordination, and psychiatric and cognitive complications.

Spirulina platensis and Phaeodactylum tricornutum as sustainable sources of bioactive compounds: Health implications and applications in the food industry

AbstractThe exponential growth of the global population, coupled with issues of insufficient and imbalanced nutrition, as well as a surge in health‐related problems, has compelled individuals to seek innovative and alternative food sources while optimizing existing resources. Microalgae have been a staple source of livelihood and essential nourishment for people in various regions worldwide. Their rich content of proteins, essential amino acids, carbohydrates, lipids, vitamins, and minerals necessary for nutrition, has made them a fundamental source of sustenance. Spirulina platensis (S. platensis), a single‐celled, filamentous, prokaryotic microalgae, has long been recognized as a valuable natural food source, with historical usage dating back to ancient times. On the other hand, Phaeodactylum tricornutum (P. tricornutum), although a freshwater species, belongs to the Pennateae group of single‐celled eukaryotic diatoms and exhibits adaptability to marine environments. S. platensis and P. tricornutum have recently gained attention due to their abundant bioactive compounds, including carotenoids and phenolic acids. These bioactive compounds are known for their potential health benefits, including anticancer, antioxidant, anti‐inflammatory, neuroprotective, hepatoprotective, and hypocholesterolemic properties. This review examines the bioactive compounds produced by S. platensis and P. tricornutum, their impacts on human health, and their promising applications within the food industry.

An Update on Stiripentol Mechanisms of Action: A Narrative Review.

Stiripentol (Diacomit®) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABAA receptors, especially those containing α3 and δ subunits. Blockade of voltage-gated sodium and T-type calcium channels, which is classically associated with anticonvulsant and neuroprotective properties, has also been demonstrated for STP. Finally, several studies indicate that STP could regulate glucose energy metabolism and inhibit lactate dehydrogenase. STP is also an inhibitor of several cytochrome P450 enzymes involved in the metabolism of other ASMs, contributing to boost their anticonvulsant efficacy as add-on therapy. These different MoAs involved in treatment of DS and recent data suggest a potential for STP to treat other neurological or non-neurological diseases.

Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases.

Nature is an important source of bioactive compounds and has continuously made a large contribution to the discovery of new drug leads. Particularly, plant-derived compounds have long been identified as highly interesting in the field of aging research and senescence. Many plants contain bioactive compounds that have the potential to influence cellular processes and provide health benefits. Among them, Piper alkaloids have emerged as interesting candidates in the context of age-related diseases and particularly senescence. These compounds have been shown to display a variety of features, including antioxidant, anti-inflammatory, neuroprotective, and other bioactive properties that may help counteracting the effects of cellular aging processes. In the review, we will put the emphasis on piperlongumine and other related derivatives, which belong to the Piper alkaloids, and whose senomodulating potential has emerged during the last several years. We will also provide a survey on their potential in therapeutic perspectives of age-related diseases.

(063) Effect of Phosphodiesterase Type 4 Inhibitor on Erectile Function Recovery and Nerve Regeneration After Cavernous Nerve Injury in Rats

Abstract Introduction There is no consensus on the best treatment regimen for recovery of erectile function (EF) after radical prostatectomy (RP). Although many pharmacological interventions can improve EF in rats, there is still a lack of studies evaluating strategies that promote nerve regeneration of the cavernous nerve (CN). Phosphodiesterase type 4 inhibitors (PDE4Is), such as rolipram, have shown a neuroprotective effect after spinal cord injury in mice, facilitating functional recovery. It has also been suggested that the neuroprotective property of sildenafil is probably attributed to its effect on phosphodiesterase type 4. Objective Our aim was to evaluate the role of rolipram and its association with tadalafil in EF recovery and nerve regeneration after bilateral CN crush injury (BCNI) in rats. Methods Thirty-five male Wistar rats were randomly divided into four groups: (i) sham (no CN lesion); (ii) control (no treatment after BCNI); (iii) BCNI + tadalafil; (iv) BCNI + rolipram and (v) BCNI + tadalafil + rolipram. The initial laparotomy was performed and the CN were crushed with a hemostatic clamp. The animals in groups (iii) and (iv) received tadalafil (5mg/kg/d) or rolipram (1mg/kg/d) orally for 14 days, respectively. The animals in group (v) received tadalafil + rolipram at the same doses. Then, the animals were submitted to CN stimulation at frequencies 4, 8 and 16 Hz, with recording of mean arterial pressure (MAP) and intracavernosal pressure (ICP). EF was represented by the measurement of maximum ICP normalized to MAP (ICP/MAP ratio) and total normalized area under the curve (AUC) of ICP. The penises and CN of the animals were sent for structural evaluation with the immunohistochemical markers S100 and Ki-67. Results In the functional analysis, BCNI resulted in worse EF when compared to sham. This was observed when considering the maximum ICP/MAP and when analyzing normalized AUC of ICP for 4Hz and 8Hz. The different treatments were able to increase the ICP/MAP ratio after stimulation with 4Hz (p = 0.04) and 8Hz (p = 0.01). When considering normalized AUC of ICP, the different drugs (tadalafil, rolipram or tadalafil + rolipram) showed a significant improvement in EF in two of the three frequencies analyzed (4Hz and 8Hz) (figure 1). For 16hz, although it did not reach a statistical difference, a trend of improvement was observed after the different treatments (p = 0.08). With regard to immunohistochemical analysis, the tadalafil group had a higher expression of S100 in the dorsal penile nerve compared to the control group (p = 0.01). The rolipram group had a lower expression of Ki-67 in the CN compared to the control group (p = 0.03). Conclusions The combination of tadalafil and rolipram was associated with a functional improvement in EF in the experimental model with rats. The present study also suggests that rolipram may have a neuroprotective effect according to the structural evaluation of the CN. Disclosure No.

Integrated UHPLC-Q-Orbitrap-MS/MS Method and Network Pharmacology for Exploring the Active Components and Potential Mechanisms of Neuroprotective Effect of the n-Butanol Part of Mume Flos

Background: Mume Flos is a common Qi-regulating medication used in traditional Chinese medicine, modern study has discovered that Mume Flos and its components have neuroprotective properties. However, the effective components and molecular mechanisms of Mume Flos are still unclear. Methods: In this study, the current study chose Caenorhabditis elegans as a model to evaluate the anti-Alzheimer disease (AD) effect of the active parts of Mume Flos using life span, paralysis rate, oxidative stress capacity, and heat stress capacity as indicators. Then, UHPLC-Q-Orbitrap-MS/MS and network pharmacology combined with GEO database chip were used for joint analysis to predict the active components and potential molecular mechanisms, which were validated using C. elegans models. Results: The results showed that the n-butanol part of Mume Flos slowed down nematode paralysis and possessed anti-AD activity, and we tentatively identified a total of 45 constituents, mainly including flavonoids and phenylpropanoids as well as a small number of amino acids, and determined that 39 active components and 130 targets are related to neuroprotection. Further analysis identified the main active ingredients such as rutin, neochlorogenic acid, and chlorogenic acid, all of which could reduce Aβ deposition in nematodes and slow down the rate of paralysis in transgenic nematodes. Conclusion: This study revealed the neuroprotective effects of MFB and identified its active components as rutin, neochlorogenic acid, and chlorogenic acid. They may play a role in reducing Aβ deposition by regulating the targets of GAPDH, TNF, IL6, INS, and TP53. This study provides a basis for further in-depth research on the mechanism of MFB to improve neurological diseases.