23,357 results on '"Neuroprotective Agents"'
Search Results
2. Intra-arterial Neuroprotective Strategy for Ischemic STroke Patients With Endovascular Therapy (INSIST-ET)
- Author
-
Hui-Sheng Chen, Director
- Published
- 2024
3. Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach (PROMESA)
- Author
-
German Center for Neurodegenerative Diseases (DZNE), Deutsche Parkinson Vereinigung, German Foundation for Neurology, ParkinsonFonds Deutschland gGmbH, and Dr. Johannes Levin, Sponsor delegated person
- Published
- 2024
4. Exploring the neuroprotective potential of Nrf2-pathway activators against annonacin toxicity.
- Author
-
Costa, Márcia F. D., Rösler, Thomas W., and Höglinger, Günter U.
- Subjects
- *
NEUROPROTECTIVE agents , *TAUOPATHIES , *CELL survival , *NEURODEGENERATION , *CELLULAR signal transduction , *DOPAMINE receptors , *FAMILIAL spastic paraplegia - Abstract
Modulation of the Nrf2 pathway, a master regulator of the antioxidant response and cellular metabolism, has been suggested as a promising therapeutic strategy in tauopathies, a heterogeneous group of neurodegenerative disorders characterized by intracellular proteinaceous inclusions of abnormally phosphorylated tau. Here, we explored the neuroprotective potential of different Nrf2-pathway activators in human immortalized dopaminergic neurons against annonacin-induced toxicity, a mitochondrial inhibitor associated with a PSP-like syndrome and capable of mimicking tauopathy-like features. Interestingly, we observed heterogenous and compound-dependent neuroprotective effects among the different Nrf2-pathway activators. With the exception of Fyn inhibitors, all the selected Nrf2-pathway activators improved cell viability and the oxidative status, and reduced the annonacin-induced tau hyperphosphorylation and neurite degeneration, particularly the p62-activators. However, improvement of the impaired mitochondrial function was only observed by the Bach-1 inhibitor. Surprisingly, we found evidence that ezetimibe, an approved drug for hypercholesterolemia, prevents the transcriptional upregulation of 4R-tau triggered by annonacin insult. Overall, our results suggest that the neuroprotective effects of the Nrf2-pathway activators against annonacin toxicity may rely on the specific mechanism of action, intrinsic to each compound, and possibly on the concomitant modulation of additional signaling pathways. Further research will be needed to fully understand how synergistic modulation of metabolic adaptation and cell survival can be exploit to develop new therapeutical strategies for tauopathies and eventually other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Insect-derived extracts and peptides in neuroprotection.
- Author
-
Bhola, Shivam, Park, Eun-Jung, and Lee, Hae-Jeung
- Subjects
- *
EDIBLE insects , *NEUROPROTECTIVE agents , *PEPTIDES , *NEURODEGENERATION , *NEUROLOGICAL disorders - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. One flask cascade approach to a complex pyrano[2,3-c]pyrazole-pyrazolone hybrid heterocyclic system and its initiatory neurobiological profiling.
- Author
-
Balasubramani, Alagesan, Sudarshana, K. A., Kushwaha, Roli, Chakravarty, Sumana, Pabbaraja, Srihari, and Mehta, Goverdhan
- Subjects
- *
SUSTAINABLE chemistry , *PYRAZOLONES , *RING formation (Chemistry) , *CONDENSATION , *NEUROPROTECTIVE agents - Abstract
A one-pot multicomponent approach towards a hybrid heterocyclic pyrano[2,3-c]pyrazole-pyrazolone framework involving tandem Knoevenagel condensation, sequential intermolecular 1,6-Michael addition, and 6-endo dig cyclization between diynones and pyrazolones, mediated by DBU, has been discovered. This process embodies several green and sustainable chemistry features. Preliminary bioactivity profiling of the new chemical entities indicates neuroprotective and AChE inhibitory activities. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Correction: Neuroprotective effects of Shende'an tablet in the Parkinson's disease model.
- Author
-
Sheng, Xiaoyan, Yang, Shuiyuan, Wen, Xiaomin, Zhang, Xin, Ye, Yongfeng, Zhao, Peng, Zang, Limin, Peng, Kang, Du, Enming, and Li, Sai
- Subjects
- *
DRUG therapy for Parkinson's disease , *NEUROPROTECTIVE agents , *PHARMACODYNAMICS - Published
- 2024
- Full Text
- View/download PDF
8. Neuroprotective and antioxidant activities of Colombian plants against paraquat and C2-ceramide exposure in SH-SY5Y cells.
- Author
-
Bustos-Rangel, Angie, Muñoz-Cabrera, Jonathan, Cuca, Luis, Arboleda, Gonzalo, Ávila Murillo, Mónica, and Sandoval-Hernández, Adrián G.
- Subjects
NEUROPROTECTIVE agents ,ANTIOXIDANTS ,CERAMIDES ,REACTIVE oxygen species ,PHYTOCHEMICALS - Abstract
Abnormal production of reactive oxygen species (ROS) has been implicated in the physiopathology of neuronal cell death. Increased ROS levels are associated with exacerbated peptide aggregation, inflammation, and mitochondrial dysfunction, which facilitate the triggering of specific cell death pathways. Antioxidant molecules are potentially useful in the amelioration of neurodegeneration. In this regard, natural products are an invaluable source of antioxidants. Therefore, we investigate the antioxidant and neuroprotective activities of four Colombian angiosperm extracts. Antioxidant activity was evaluated by phytochemical assays using TLC techniques with Dragendorff reagent, ninhydrin, and chloranil in dioxane, NH3, Fast Blue, and FeCl3, together with bioautography using DPPH and β-carotene. In vitro neuroprotective activity, cell death, and ROS accumulation were evaluated by MTT and flow cytometry in the SH-SY5Y cell line exposed to paraquat and C2-ceramide. We found that Zanthoxylum rhoifolium Lam, Zanthoxylum martinicense, Nectandra membranacea, and Nectandra reticulata extracts have antioxidant activity higher than quercetin under a β-carotene bleaching assay and protect SH-SY5Y cells against paraquat and C2-ceramide associated with a reduction in ROS. In conclusion, these extracts have a strong neuroprotective potential, and the precise mechanism requires more evaluation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. Danggui Shaoyao San and disassembled prescription: neuroprotective effects via AMPK/mTOR-mediated autophagy in mice.
- Author
-
Cheng, Xiaoqing, Dai, Yuqiong, Shang, Baoling, Zhang, Shuting, Lin, Liting, Wu, Qingguang, Zhan, Ruoting, Li, Shengqing, and Liu, Sijun
- Subjects
CHINESE medicine ,NEUROPROTECTIVE agents ,TAU proteins ,COMPUTER-assisted molecular modeling ,ALZHEIMER'S disease ,AUTOPHAGY ,RESEARCH funding ,HERBAL medicine ,PHARMACEUTICAL chemistry ,ENZYME-linked immunosorbent assay ,NEURONS ,AMP-activated protein kinases ,CELLULAR signal transduction ,IN vivo studies ,REVERSE transcriptase polymerase chain reaction ,NEUROINFLAMMATION ,DESCRIPTIVE statistics ,MICE ,IMMUNOHISTOCHEMISTRY ,MESSENGER RNA ,ANIMAL experimentation ,WESTERN immunoblotting ,COGNITION disorders ,ANALYSIS of variance ,STAINS & staining (Microscopy) ,DATA analysis software ,INTERLEUKINS ,TUMOR necrosis factors ,PHARMACODYNAMICS - Abstract
Background: Danggui Shaoyao San (DSS), a frequently prescribed Chinese medicine formula, has demonstrated clinical efficacy in the treatment of Alzheimer's disease (AD). This study aims to explore the differences in therapeutic effects of DSS and its disassembled prescriptions, Suangan (SG) and Xingan (XG), in treating Alzheimer's Disease and the mechanism of DSS recovering autophagy in AD. Methods: A network pharmacology strategy was employed to delineate the bioactive constituents, associated targets, and regulatory mechanisms of DSS in AD, encompassing in silico target forecasting, the generation and scrutiny of PPI networks, alongside GO and KEGG-based pathway elucidation. An AD mouse model, induced by intracerebroventricular injection of Aβ
1–42 , was used to evaluate the therapeutic effects of DSS and its disassembled prescriptions on AD. Cognitive function was evaluated using the Morris water maze. Expression levels of inflammatory cytokines were quantified via RT-qPCR and ELISA. Western blotting was used to detect the expression of proteins related to AD pathological markers and the AMPK/mTOR signaling pathway. Results: 50 active compounds and 718 HUB genes were screened from relevant databases and literature. KEGG and GO analyses indicated that DSS's potential mechanisms against AD involved the AMPK/mTOR signaling pathway and mitophagy. In vivo animal model, the results demonstrated that DSS, SG, and XG treatments improved cognitive function and ameliorated neuroinflammation in mice. Additionally, they alleviated the pathological changes of neuronal cells. These treatments also increased the protein level of PSD-95, and decreased levels of APP and p-Tau. Among them, DSS exhibited the best efficacy. Furthermore, DSS, SG, and XG upregulated the expression of LC3, Beclin1, and p-AMPK, while decreasing the expression of P62 and p-mTOR. Conclusions: DSS, SG, and XG were found to ameliorate AD-related pathological symptoms in Aβ1−42 -injected mice, likely through the AMPK/mTOR autophagy signaling pathway. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
10. Neuroprotective and Neurite Outgrowth Stimulating Effects of New Low-Basicity 5-HT7 Receptor Agonists: In Vitro Study in Human Neuroblastoma SH-SY5Y Cells.
- Author
-
Jakubowska, Klaudia, Hogendorf, Adam S., Gołda, Sławomir, and Jantas, Danuta
- Subjects
- *
SEROTONIN receptors , *NEUROBLASTOMA , *NEUROPROTECTIVE agents , *HUMAN experimentation , *CELL culture , *TRETINOIN - Abstract
There is some evidence that the serotonin receptor subtype 7 (5-HT7) could be new therapeutic target for neuroprotection. The aim of this study was to compare the neuroprotective and neurite outgrowth potential of new 5-HT7 receptor agonists (AH-494, AGH-238, AGH-194) with 5-CT (5-carboxyamidotryptamine) in human neuroblastoma SH-SY5Y cells. The results revealed that 5-HT7 mRNA expression was significantly higher in retinoic acid (RA)-differentiated cells when compared to undifferentiated ones and it was higher in cell cultured in neuroblastoma experimental medium (DMEM) compared to those placed in neuronal (NB) medium. Furthermore, the safety profile of compounds was favorable for all tested compounds at concentration used for neuroprotection evaluation (up to 1 μM), whereas at higher concentrations (above 10 μM) the one of the tested compounds, AGH-194 appeared to be cytotoxic. While we observed relatively modest protective effects of 5-CT and AH-494 in UN-SH-SY5Y cells cultured in DMEM, in UN-SH-SY5Y cells cultured in NB medium we found a significant reduction of H2O2-evoked cell damage by all tested 5-HT7 agonists. However, 5-HT7-mediated neuroprotection was not associated with inhibition of caspase-3 activity and was not observed in RA-SH-SY5Y cells exposed to H2O2. Furthermore, none of the tested 5-HT7 agonists altered the damage induced by 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenylpyridinium ion (MPP +) and doxorubicin (Dox) in UN- and RA-SH-SY5Y cells cultured in NB. Finally we showed a stimulating effect of AH-494 and AGH-194 on neurite outgrowth. The obtained results provide insight into neuroprotective and neurite outgrowth potential of new 5-HT7 agonists. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. Development and Optimization of Nasal Composition of a Neuroprotective Agent for Use in Neonatology after Prenatal Hypoxia.
- Author
-
Belenichev, Igor, Aliyeva, Olena, Burlaka, Bogdan, Burlaka, Kristina, Kuchkovskyi, Oleh, Savchenko, Dmytro, Oksenych, Valentyn, and Kamyshnyi, Oleksandr
- Subjects
- *
INTRANASAL administration , *DRUG administration routes , *CENTRAL nervous system , *NEUROPROTECTIVE agents , *BLOOD-brain barrier , *PHARMACEUTICAL gels - Abstract
The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system (CNS), bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. The creation of new dosage forms for neonatology using mathematical technologies and special software in pharmaceutical development allows for the creation of cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a new nasal gel formulation with Angiolin using a Box-Behnken experiment design for the therapy of prenatal CNS damage. It was found that the consistency characteristics of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component—sodium salt of carboxymethylcellulose. We optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized nasal gel composition demonstrated satisfactory thixotropic properties. The 1% gel for neuroprotection with Angiolin, developed for intranasal administration, meets all safety requirements for this group of drug forms, showing low toxicity and no local irritant or allergic effects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
12. Efficient Two-Step Synthesis of Novel Pyrimido[4,5- d ] Pyrimidines with Potent Neuroprotective, Antioxidant, and A β Anti-Aggregation Properties.
- Author
-
Ben Ameur, Ghada, Maalej, Emna, Martin, Helene, Jacquinot, Anne-Sophie, Barbanneau, Nadine, Bernard, Paul J., Marco-Contelles, José, Chabchoub, Fakher, and Ismaili, Lhassane
- Subjects
- *
ALZHEIMER'S disease , *NEUROPROTECTIVE agents , *OXIDATIVE stress , *PYRIMIDINES , *ANTIOXIDANTS - Abstract
Eleven new differently substituted N,7-diphenylpyrimido [4,5-d]pyrimidin-4-amines 4a–k were synthesized from readily available reagents in a simple and inexpensive two-step procedure with yields up to 57%. Neuroprotective analysis against H2O2 and analysis using ORAC assays identified compounds 4g, 4i and 4j as promising antioxidant compounds. These compounds also showed potent inhibition of Aβ1–42 self-aggregation, and suitable physicochemical properties predicted by Datawarior software V6.1.0, this biological activity and physicochemical property being of great interest for pathologies linked to oxidative stress, such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
13. Discovery of palmatine derivatives as potent neuroprotective agents.
- Author
-
Pang, Shuo, Chen, Na, Li, Zhuo, Luo, Zhuo-Hui, Dong, Wei, Gao, Shan, Liu, Ning, Pan, Shuo, Zhang, Lian-Feng, Chen, Jun, and Yang, Ya-Jun
- Subjects
- *
ALZHEIMER'S disease prevention , *CHINESE medicine , *NEUROPROTECTIVE agents , *DRUG toxicity , *IN vitro studies , *ALZHEIMER'S disease , *RESEARCH funding , *LIQUID chromatography-mass spectrometry , *T-test (Statistics) , *HERBAL medicine , *CELL physiology , *NEURODEGENERATION , *BIOCHEMISTRY , *IMMUNODIAGNOSIS , *OXIDATIVE stress , *DESCRIPTIVE statistics , *MEDICINAL plants , *DRUG efficacy , *HYDROGEN peroxide , *SPECTRUM analysis , *BIOLOGICAL assay , *STAINS & staining (Microscopy) , *DRUG discovery , *CELL surface antigens , *NONPARAMETRIC statistics , *PHARMACODYNAMICS - Abstract
Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
14. Bioactivities and Toxicity of the Golden Camellia Species: A Systematic Review.
- Author
-
Minh-Nhut Truong, The-Long Pham, Tram-Anh Mai Pham, Van-Dat Truong, Linh-Tu Vo, Thao-My Nguyen-Hoang, and Lac-Thuy Nguyen-Huu
- Subjects
CAMELLIAS ,SPECIES ,ANTIDEPRESSANTS ,NEUROPROTECTIVE agents - Abstract
Golden camellia, a group of herbal materials belonging to the Theaceae family, was widely distributed in Asian countries, particularly Vietnam and southern China. Numerous pharmacological effects of various golden camellia species have been reported in reputable databases such as PubMed and Google Scholar. These effects included anti-tumor, lipid-lowering, anxiolytic, antidepressant, neuroprotective, antioxidant, antibacterial, and anti-inflammatory properties. Furthermore, toxicity studies on golden camellia species have demonstrated their safety for use. Our systematic review provides a comprehensive understanding of the pharmacological effects and safety of various golden camellia species, aiming to provide reliable evidence for the clinical use of this herbal material. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
15. Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.
- Author
-
Li, Zhong-hao, Pu, Xiao-qi, Li, Sha-sha, Dong, Xiao-ke, Zhang, Guo-qiang, Wang, Yu, and Liu, Jin-min
- Subjects
CHINESE medicine ,NEUROPROTECTIVE agents ,BIOLOGICAL models ,COMPUTER-assisted molecular modeling ,INTRAPERITONEAL injections ,PROTEIN kinases ,HERBAL medicine ,PHARMACEUTICAL chemistry ,TREATMENT effectiveness ,IN vivo studies ,CELLULAR signal transduction ,RATS ,GENE expression ,ISCHEMIC stroke ,ANIMAL experimentation ,WESTERN immunoblotting ,CEREBRAL infarction ,INTRAVENOUS injections ,CELL receptors ,DRUG dosage ,THERAPEUTICS ,DRUG administration - Abstract
Objective: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. Methods: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. Results: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. Conclusions: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve.
- Author
-
Wang, Yuan, Zheng, A-ni, Yang, Huan, Wang, Qiang, Dai, Biao, Wang, Jia-ju, Wan, Yi-tong, Liu, Zhi-bin, and Liu, Si-yang
- Subjects
ALZHEIMER'S disease treatment ,NEUROPROTECTIVE agents ,CHINESE medicine ,DATA analysis ,NEUROPLASTICITY ,GUT microbiome ,APOPTOSIS ,BRAIN ,TREATMENT effectiveness ,DESCRIPTIVE statistics ,CELLULAR signal transduction ,GASTROINTESTINAL system ,ELECTROACUPUNCTURE ,MICE ,RNA ,ELECTRIC stimulation ,COGNITION disorders ,ANIMAL experimentation ,WESTERN immunoblotting ,ANALYSIS of variance ,ONE-way analysis of variance ,STATISTICS ,BRAIN-derived neurotrophic factor ,OLFACTORY nerve ,HIPPOCAMPUS (Brain) ,DATA analysis software ,SEQUENCE analysis ,NONPARAMETRIC statistics - Abstract
Objective: To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. Methods: Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively. Results: Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P<0.05 or P<0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P<0.05 or P<0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P<0.05 or P<0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella (P<0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P<0.05 or P<0.01). Conclusions: OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer's disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. Medicinal herbal remedies in neurodegenerative diseases: an update on antioxidant potential.
- Author
-
Sarkar, Biplob, Rana, Nitasha, Singh, Charan, and Singh, Arti
- Subjects
NEURODEGENERATION ,SCIENCE databases ,NEUROPROTECTIVE agents ,MEDICAL research ,PLANT extracts - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. The effect of salidroside in promoting endogenous neural regeneration after cerebral ischemia/reperfusion involves notch signaling pathway and neurotrophic factors.
- Author
-
Zheng, Jiabing, Zhang, Jizhou, Han, Jing, Zhao, Zhichang, and Lin, Kan
- Subjects
BIOLOGICAL models ,NEUROPROTECTIVE agents ,REPERFUSION injury ,RESEARCH funding ,DATA analysis ,ENZYME-linked immunosorbent assay ,NEUROGLIA ,NEURONS ,ROSEROOT ,CELLULAR signal transduction ,REVERSE transcriptase polymerase chain reaction ,DESCRIPTIVE statistics ,FLUORESCENT antibody technique ,PLANT extracts ,RATS ,MESSENGER RNA ,GENE expression ,GLYCOSIDES ,NERVOUS system regeneration ,BRAIN-derived neurotrophic factor ,ANIMAL experimentation ,WESTERN immunoblotting ,ONE-way analysis of variance ,STATISTICS ,CEREBRAL ischemia ,STAINS & staining (Microscopy) ,DATA analysis software ,COMPARATIVE studies ,BIOMARKERS ,NERVE growth factor - Abstract
Background: Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism. Methods: Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR. Results: Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2'-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration. Conclusions: Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. Selective COX-2 Inhibitors as Neuroprotective Agents in Traumatic Brain Injury.
- Author
-
Hiskens, Matthew I., Schneiders, Anthony G., and Fenning, Andrew S.
- Subjects
BRAIN injuries ,CYCLOOXYGENASE 2 inhibitors ,TREATMENT effectiveness ,REACTIVE oxygen species ,NEUROPROTECTIVE agents - Abstract
Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. Prenylated dihydroflavones from the root barks of Morus alba.
- Author
-
Zhu, Jun-Yu, Weng, Han-Zhuang, Tang, Di-Kai, Long, Jin-Chen, Tang, Zhuo-Ya, Chen, Ye, Yin, Sheng, and Tang, Gui-Hua
- Subjects
WHITE mulberry ,ELLAGIC acid ,EDARAVONE ,PHEOCHROMOCYTOMA ,NEUROPROTECTIVE agents - Abstract
Three new prenylated dihydroflavones, moralbaflavones A–C (1–3), together with four known ones (4a/4b, 5, and 6) were isolated from the root barks of Morus alba L. Their structures including the absolute configurations were determined by the analysis of HRMS, NMR, and ECD data. The neuroprotective properties of these prenylated dihydroflavones were screened at the concentration of 10 µM in the sodium nitroprusside-induced rat pheochromocytoma PC-12 cells, and the results showed moralbaflavone C (3) possessed significant neuroprotective activity, being more potent than the positive control edaravone. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
21. The relationship between hypoxia and Alzheimer's disease: an updated review.
- Author
-
Borui Tao, Wei Gong, Chengyuan Xu, Zhihui Ma, Jinyu Mei, and Ming Chen
- Subjects
BRAIN physiology ,HYPERTENSION epidemiology ,THERAPEUTIC use of antioxidants ,ALZHEIMER'S disease risk factors ,PROTEINS ,TAU proteins ,RISK assessment ,MIDDLE-income countries ,NEUROPROTECTIVE agents ,UBIQUINONES ,ALZHEIMER'S disease ,OXYGEN ,CARDIOVASCULAR diseases ,DEVELOPED countries ,OXIDATIVE stress ,NEURODEGENERATION ,CELLULAR signal transduction ,BURDEN of care ,ANTI-infective agents ,AMYLOID plaque ,DEMENTIA ,MITOCHONDRIAL pathology ,INFLAMMATION ,PSYCHOLOGY of caregivers ,TRYPTOPHAN ,BRAIN injuries ,CYTOKINES ,HYPOXEMIA ,AMYLOID beta-protein precursor ,LOW-income countries ,DIABETES ,ACTIVE aging ,DISEASE complications - Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and the most prevalent form of dementia. The main hallmarks for the diagnosis of AD are extracellular amyloid-beta (Aβ) plaque deposition and intracellular accumulation of highly hyperphosphorylated Tau protein as neurofibrillary tangles. The brain consumes more oxygen than any other organs, so it is more easily to be affected by hypoxia. Hypoxia has long been recognized as one of the possible causes of AD and other neurodegenerative diseases, but the exact mechanism has not been clarified. In this review, we will elucidate the connection between hypoxia-inducible factors-1α and AD, including its contribution to AD and its possible protective effects. Additionally, we will discuss the relationship between oxidative stress and AD as evidence show that oxidative stress acts on AD-related pathogenic factors such as mitochondrial dysfunction, Aβ deposition, inflammation, etc. Currently, there is no cure for AD. Given the close association between hypoxia, oxidative stress, and AD, along with current research on the protective effects of antioxidants against AD, we speculate that antioxidants could be a potential therapeutic approach for AD and worth further study. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.
- Author
-
Petrova, Veselina, Snavely, Andrew R., Splaine, Jennifer, Zhen, Shannon, Singh, Bhagat, Pandey, Roshan, Chen, Kuchuan, Cheng, Anya, Hermawan, Crystal, Barrett, Lee B., Smith, Jennifer A., and Woolf, Clifford J.
- Subjects
- *
CHEMOTHERAPY complications , *NEUROPROTECTIVE agents , *MOTOR neurons , *SENSORY neurons , *NEURONS - Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of cancer chemotherapy that can often limit treatment options for cancer patients or have life-long neurodegenerative consequences that reduce the patient's quality of life. CIPN is caused by the detrimental actions of various chemotherapeutic agents on peripheral axons. Currently, there are no approved preventative measures or treatment options for CIPN, highlighting the need for the discovery of novel therapeutics and improving our understanding of disease mechanisms. In this study, we utilized human-induced pluripotent stem cell (hiPSC)-derived motor neurons as a platform to mimic axonal damage after treatment with vincristine, a chemotherapeutic used for the treatment of breast cancers, osteosarcomas, and leukemia. We screened a total of 1902 small molecules for neuroprotective properties in rescuing vincristine-induced axon growth deficits. From our primary screen, we identified 38 hit compounds that were subjected to secondary dose response screens. Six compounds showed favorable pharmacological profiles – AZD7762, A-674563, Blebbistatin, Glesatinib, KW-2449, and Pelitinib, all novel neuroprotectants against vincristine toxicity to neurons. In addition, four of these six compounds also showed efficacy against vincristine-induced growth arrest in human iPSC-derived sensory neurons. In this study, we utilized high-throughput screening of a large library of compounds in a therapeutically relevant assay. We identified several novel compounds that are efficacious in protecting different neuronal subtypes from the toxicity induced by a common chemotherapeutic agent, vincristine which could have therapeutic potential in the clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. Dexmedetomidine administration as a possible cognitive enhancer through increasing the level of brain-derived neurotrophic factors in surgical patients: a systematic review and meta-analysis.
- Author
-
Dehbozorgi, Masoud, Fereidooni, Fatemeh, Bozorgmehr, Ramin, Bagherpour, Javad Zebarjadi, Shafiee, Arman, Mohammadi, Ida, Amini, Mohammad Javad, Seighali, Niloofar, Jafarabady, Kyana, Rajai Firouzabadi, Shahryar, Akbarzade, Diba, and Bahri, Razman Arabzadeh
- Subjects
- *
MEDICAL information storage & retrieval systems , *NEUROPROTECTIVE agents , *SURGERY , *PATIENTS , *TREATMENT effectiveness , *META-analysis , *DESCRIPTIVE statistics , *SYSTEMATIC reviews , *MEDLINE , *BRAIN-derived neurotrophic factor , *ONLINE information services , *CONFIDENCE intervals , *QUALITY assurance , *IMIDAZOLES , *COGNITION , *ANESTHESIA , *PERIOPERATIVE care , *BLOOD - Abstract
Objective: This meta-analysis aimed to investigate the effect of dexmedetomidine on brain-derived neurotrophic factor (BDNF) levels in individuals undergoing various medical procedures. We systematically searched electronic databases and manually identified relevant articles to assess the impact of dexmedetomidine on BDNF levels in surgical patients. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Embase, and Web of Science databases with no language restrictions. Studies that examined the effects of dexmedetomidine administration on BDNF levels in surgical patients were included. Results: The overall analysis revealed a statistically significant increase in BDNF levels in individuals receiving dexmedetomidine compared to controls (Standardized Mean Difference SMD = 1.65, 95% CI: 1.02 to 2.28; I2: 89%). Subgroup analyses based on the anesthesia method (p < 0.01), and the type of surgery (p < 0.01) showed significant between-group differences (Fig. 3). The results of the sensitivity analyses indicated that individual studies did not significantly affect the overall results. Conclusion: This meta-analysis indicates that dexmedetomidine administration is associated with a significant increase in BDNF levels in individuals undergoing surgical procedures. These findings highlight the potential role of dexmedetomidine in modulating BDNF levels, which may have implications for optimizing perioperative neuroprotective strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs.
- Author
-
Yanxin Shen, Meng Zhao, Panpan Zhao, Lingjie Meng, Yan Zhang, Guimei Zhang, Yezi Taishi, and Li Sun
- Subjects
ALZHEIMER'S disease ,LITHIUM carbonate ,DONEPEZIL ,LITHIUM ,DEVELOPMENTAL neurobiology ,NEUROPROTECTIVE agents ,MOOD stabilizers ,GLYCOGEN synthase kinase-3 - Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Despite advances in understanding the pathophysiological mechanisms of AD, effective treatments remain scarce. Lithium salts, recognized as mood stabilizers in bipolar disorder, have been extensively studied for their neuroprotective effects. Several studies indicate that lithium may be a disease-modifying agent in the treatment of AD. Lithium’s neuroprotective properties in AD by acting on multiple neuropathological targets, such as reducing amyloid deposition and tau phosphorylation, enhancing autophagy, neurogenesis, and synaptic plasticity, regulating cholinergic and glucose metabolism, inhibiting neuroinflammation, oxidative stress, and apoptosis, while preserving mitochondrial function. Clinical trials have demonstrated that lithium therapy can improve cognitive function in patients with AD. In particular, meta-analyses have shown that lithium may be a more effective and safer treatment than the recently FDA-approved aducanumab for improving cognitive function in patients with AD. The affordability and therapeutic efficacy of lithium have prompted a reassessment of its use. However, the use of lithium may lead to potential side effects and safety issues, which may limit its clinical application. Currently, several new lithium formulations are undergoing clinical trials to improve safety and efficacy. This review focuses on lithium’s mechanism of action in treating AD, highlighting the latest advances in preclinical studies and clinical trials. It also explores the side effects of lithium therapy and coping strategies, offering a potential therapeutic strategy for patients with AD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Exploring the therapeutic potential of Aloin: unraveling neuroprotective and anticancer mechanisms, and strategies for enhanced stability and delivery.
- Author
-
Zimbone, Stefania, Romanucci, Valeria, Zarrelli, Armando, Giuffrida, Maria Laura, Sciacca, Michele F. M., Lanza, Valeria, Campagna, Tiziana, Maugeri, Ludovica, Petralia, Salvatore, Consoli, Grazia Maria Letizia, Di Fabio, Giovanni, and Milardi, Danilo
- Subjects
- *
QUANTUM dots , *DRUG delivery systems , *NEUROPROTECTIVE agents , *ALOE vera , *HELA cells - Abstract
We investigate the therapeutic potential of Aloin A and Aloin B, two natural compounds derived from Aloe vera leaves, focusing on their neuroprotective and anticancer properties. The structural differences between these two epimers suggest that they may exhibit distinct pharmacological properties. Our investigations revealed that both epimers are not stable in aqueous solution and tend to degrade rapidly, with their concentration decreasing by over 50% within approximately 12 h. These results underscore the importance of addressing issues such as the need for encapsulation into effective drug delivery systems to enhance stability. ThT fluorescence experiments showed that neither compound was able to inhibit Aβ amyloid aggregation, indicating that other mechanisms may be responsible for their neuroprotective effects. Next, an equimolar mixture of Aloin A and Aloin B demonstrated an ability to inhibit proteasome in tube tests, which is suggestive of potential anticancer properties, in accordance with antiproliferative effects observed in neuroblastoma SH-SY5Y and HeLa cell lines. Higher water stability and increased antiproliferative activity were observed by encapsulation in carbon dot nanoparticles, suggesting a promising potential for further in vivo studies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Genus Sambucus : Exploring Its Potential as a Functional Food Ingredient with Neuroprotective Properties Mediated by Antioxidant and Anti-Inflammatory Mechanisms.
- Author
-
Merecz-Sadowska, Anna, Sitarek, Przemysław, Zajdel, Karolina, Sztandera, Wiktoria, and Zajdel, Radosław
- Subjects
- *
FUNCTIONAL foods , *NEURAL stem cells , *ALZHEIMER'S disease , *PARKINSON'S disease , *NEUROPROTECTIVE agents , *CELL proliferation , *ANIMAL cognition , *OXIDATIVE stress - Abstract
The genus Sambucus, mainly Sambucus nigra, has emerged as a valuable source of bioactive compounds with potential neuroprotective properties. This review explores the antioxidant, anti-inflammatory, and neuroregenerative effects of Sambucus-derived compounds and their implications for brain health and cognitive function. In vitro studies have demonstrated the ability of Sambucus extracts to mitigate oxidative stress, modulate inflammatory responses, and promote neural stem cell proliferation and differentiation. In vivo studies using animal models of neurodegenerative diseases, such as Alzheimer's and Parkinson's, have shown that Sambucus compounds can improve cognitive function, motor performance, and neuronal survival while attenuating neuroinflammation and oxidative damage. The neuroprotective effects of Sambucus are primarily attributed to its rich content of polyphenols, particularly anthocyanins, which exert their benefits through multiple mechanisms, including the modulation of signaling pathways involved in inflammation, apoptosis, mitochondrial function, and oxidative stress. Furthermore, the potential of Sambucus as a functional food ingredient is discussed, highlighting its application in various food products and the challenges associated with the stability and bioavailability of its bioactive compounds. This review provides a comprehensive overview of the current state of research on the neuroprotective potential of Sambucus and its derivatives, offering valuable insights for the development of dietary strategies to promote brain health and prevent age-related cognitive decline. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. Recent Advances in the Distribution, Chemical Composition, Health Benefits, and Application of the Fruit of Siraitia grosvenorii.
- Author
-
Guo, Qihan, Shi, Minke, Sarengaowa, Xiao, Zhewen, Xiao, Ying, and Feng, Ke
- Subjects
DIETARY supplements ,PREVENTIVE medicine ,FRUIT ,DIET ,NEUROPROTECTIVE agents - Abstract
The fruits of Siraitia grosvenorii (S. grosvenorii) have attracted a lot of scientific interest as part of the current healthy diet. S. grosvenorii has diverse health-promoting effects, including antioxidant, anti-inflammatory, antimicrobial, respiratory modulation, metabolic modulation, antitumor, and neuroprotective effects, as well as gastrointestinal function modulation. As a plant resource, S. grosvenorii has broad application prospects, which promotes the development of the horticultural industry. Moreover, Mogroside has attracted much attention as an important active ingredient of S. grosvenorii. This review provides an in-depth exploration of the distribution, chemical composition, health benefits, and application of S. grosvenorii, particularly Mogroside. This comprehensive exploration highlights the important therapeutic potential of S. grosvenorii, prompting further research into its applications. As value-added functional ingredients, S. grosvenorii and its constituents have significant potential for disease prevention and are widely used in the development of food and health supplements. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
28. Acute Ischemic Stroke in the Clinic and the Laboratory: Targets for Translational Research.
- Author
-
Franx, Bart, Dijkhuizen, Rick M., and Dippel, Diederik W.J.
- Subjects
- *
TISSUE plasminogen activator , *ISCHEMIC stroke , *STROKE , *TRANSLATIONAL research , *NEUROPROTECTIVE agents , *HYPERPERFUSION - Abstract
• Advancements in ischemic stroke research introduce new treatment challenges. • This narrative review selectively highlights advances with clinical impact using a fictional case. • Outstanding questions are addressed that can benefit from experimental-clinical research collaborations. Ischemic stroke research has enabled significant advancements in diagnosis, treatment, and management of this debilitating disease, yet challenges remain standing in the way of better patient prognoses. In this narrative review, a fictional case illustrates challenges and uncertainties that medical professionals still face – penumbra identification, lack of neuroprotective agents, side-effects of tissue plasminogen activator, dearth of molecular biomarkers, incomplete microvascular reperfusion or no-reflow, post-recanalization hyperperfusion, blood pressure management and procedural anesthetic effects. The current state of the field is broadly reviewed per topic, with the aim to introduce a broad audience (scientist and clinician alike) to recent successes in translational stroke research and pending scientific queries that are tractable for preclinical assessment. Opportunities for co-operation between clinical and experimental stroke experts are highlighted to increase the size and frequency of strides the field makes to improve our understanding of this disease and ways of treating it. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease.
- Author
-
Hey, John A., Abushakra, Susan, Blennow, Kaj, Reiman, Eric M., Hort, Jakub, Prins, Niels D., Sheardova, Katerina, Kesslak, Patrick, Shen, Larry, Zhu, Xinyi, Albayrak, Adem, Paul, Jijo, Schaefer, Jean F., Power, Aidan, and Tolar, Martin
- Subjects
- *
NEUROPROTECTIVE agents , *ALZHEIMER'S disease , *DATA analysis , *QUESTIONNAIRES , *MAGNETIC resonance imaging , *DESCRIPTIVE statistics , *RANDOMIZED controlled trials , *APOLIPOPROTEINS , *STATISTICS , *HIPPOCAMPUS (Brain) , *BIOMARKERS , *COGNITION , *AMYLOID beta-protein precursor , *ALKANES , *GENOTYPES , *CEREBROSPINAL fluid , *CHEMICAL inhibitors - Abstract
Introduction: ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aβ) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments. Methods: The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50–80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.5 or 1], apolipoprotein E4 (APOE4) genotypes including APOE4/4 and APOE3/4 genotypes, and positive cerebrospinal fluid (CSF) AD biomarkers or prior amyloid scans. The primary outcome was plasma p-tau181, HV evaluated by magnetic resonance imaging (MRI) was the key secondary outcome, and plasma Aβ42 and Aβ40 were the secondary biomarker outcomes. The cognitive outcomes were the Rey Auditory Verbal Learning Test and the Digit Symbol Substitution Test. Safety and tolerability evaluations included treatment-emergent adverse events and amyloid-related imaging abnormalities (ARIA). The study was designed and powered to detect 15% reduction from baseline in plasma p-tau181 at the 104-week endpoint. A sample size of 80 subjects provided adequate power to detect this difference at a significance level of 0.05 using a two-sided paired t-test. Results: The enrolled population of 84 subjects (31 homozygotes and 53 heterozygotes) was 52% females, mean age 69 years, MMSE 25.7 [70% mild cognitive impairment (MCI), 30% mild AD] with 55% on cholinesterase inhibitors. Plasma p-tau181 reduction from baseline was significant (31%, p = 0.045) at 104 weeks and all prior visits; HV atrophy was significantly reduced (p = 0.0014) compared with matched external controls from an observational Early AD study. Memory scores showed minimal decline from baseline over 104 weeks and correlated significantly with decreased HV atrophy (Spearman's 0.44, p = 0.002). Common adverse events were COVID infection and mild nausea, and no drug-related serious adverse events were reported. Of 14 early terminations, 6 were due to nonserious treatment-emergent adverse events and 1 death due to COVID. There was no vasogenic brain edema observed on MRI over 104 weeks. Conclusions: The effect of ALZ-801 on reducing plasma p-tau181 over 2 years demonstrates target engagement and supports its anti-Aβ oligomer action that leads to a robust decrease in amyloid-induced brain neurodegeneration. The significant correlation between reduced HV atrophy and cognitive stability over 2 years suggests a disease-modifying effect of ALZ-801 treatment in patients with early AD. Together with the favorable safety profile with no events of vasogenic brain edema, these results support further evaluation of ALZ-801 in a broader population of APOE4 carriers, who represent two-thirds of patients with AD. Trial Registration: https://clinicaltrials.gov/study/NCT04693520. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Optimization of the Search for Neuroprotectors among Bioflavonoids.
- Author
-
Belenichev, Igor, Ryzhenko, Victor, Popazova, Olena, Bukhtiyarova, Nina, Gorchakova, Nadia, Oksenych, Valentyn, and Kamyshnyi, Oleksandr
- Subjects
- *
PROCYANIDINS , *NEUROPROTECTIVE agents , *BIOFLAVONOIDS , *EPICATECHIN , *LABORATORY animals , *CATECHIN - Abstract
For the first time, to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies; these include docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin as well as a program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules—quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, and Catechin-3-gallate—according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.15% prediction). The results of the prediction were confirmed by in vitro experiments. Course administration of catechin to animals with experimental multiple sclerosis (MS) against the background of methylprednisolone administration completely eliminated lethal cases, reduced the number of diseased animals by 20% as well as prevented the development of severe neurological symptoms by 20% (compared to the methylprednisolone group) and by 60% compared to the control group. Course administration of catechin with methylprednisolone leads to a decrease in the neurodegradation markers in the cytosol of rats, with EAE: NSE by 37% and S-100 by 54.8%. The combined administration of methylprednisolone significantly exceeds the combination of methylprednisolone with the reference drug mexidol by the degree of NSE reduction. The obtained results indicate a significant neuroprotective effect of ocular combinations of methylprednisolone and catechin. The above-mentioned confirms the correctness of the bioflavonoid selection with the help of a virtual screening program. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Assessing the Effects of Thiazole-Carboxamide Derivatives on the Biophysical Properties of AMPA Receptor Complexes as a Potential Neuroprotective Agent.
- Author
-
Qneibi, Mohammad, Hawash, Mohammed, Bdir, Sosana, Bdair, Mohammad, and Aldwaik, Samia Ammar
- Subjects
- *
NEUROPROTECTIVE agents , *ALZHEIMER'S disease , *AMPA receptors , *CENTRAL nervous system , *GLYCINE receptors , *NEUROLOGICAL disorders , *NEURAL transmission , *DRUG design , *ALLOSTERIC regulation - Abstract
An optimal balance between excitatory and inhibitory transmission in the central nervous system provides essential neurotransmission for good functioning of the neurons. In the neurology field, a disturbed balance can lead to neurological diseases like epilepsy, Alzheimer's, and Autism. One of the critical agents mediating excitatory neurotransmission is α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, which are concerned with synaptic plasticity, memory, and learning. An imbalance in neurotransmission finally results in excitotoxicity and neurological pathologies that should be corrected through specific compounds. Hence, the current study will prove to be an evaluation of new thiazole-carboxamide derivatives concerning AMPAR-modulating activity and extended medicinal potential. In the current project, five previously synthesized thiazole-carboxamide derivatives, i.e., TC-1 to TC-5, were used to interact with the AMPARs expressed in HEK293T cells, which overexpress different subunits of the AMPAR. Patch-clamp analysis was carried out while the effect of the drugs on AMPAR-mediated currents was followed with a particular emphasis on the kinetics of inhibition, desensitization, and deactivation. All tested TC compounds, at all subunits, showed potent inhibition of AMPAR-mediated currents, with TC-2 being the most powerful for all subunits. These compounds shifted the receptor kinetics efficiently, mainly enhancing the deactivation rates, and hence acted as a surrogate for their neuroprotective potentials. Additionally, recently published structure–activity relationship studies identified particular substituent groups as necessary for improving the pharmacologic profiles of these compounds. In this regard, thiazole-carboxamide derivatives, particularly those classified as TC-2, have become essential negative allosteric modulators of AMPAR function and potential therapeutics in neurological disturbances underlain by the dysregulation of excitatory neurotransmission. Given their therapeutic effectiveness and safety profiles, these in vivo studies need to be further validated, although computational modeling can be further developed for drug design and selectivity. This will open possibilities for new drug-like AMPAR negative allosteric modulators with applications at the clinical level toward neurology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
32. Antiapoptotic Effects of Hydroxychloroquine on Hypoxic–Ischemic Injury in Neonatal Rat Brain: May Hydroxychloroquine Be an Adjuvant Theraphy?
- Author
-
Tepe, Tugay, Satar, Mehmet, Yildizdas, Hacer Yapicioglu, Ozdemir, Mustafa, Ozlu, Ferda, Erdogan, Seyda, Toyran, Tugba, and Akillioglu, Kubra
- Subjects
- *
BRAIN physiology , *HYDROXYCHLOROQUINE , *NEUROPROTECTIVE agents , *CAROTID artery , *BIOLOGICAL models , *INTRAPERITONEAL injections , *CARDIOVASCULAR diseases , *PHYSIOLOGIC salines , *TISSUES , *RESEARCH funding , *APOPTOSIS , *ANTINEOPLASTIC agents , *KRUSKAL-Wallis Test , *NEURONS , *FIBRINOLYTIC agents , *LIGATURE (Surgery) , *MANN Whitney U Test , *DESCRIPTIVE statistics , *PERINATOLOGY , *RATS , *ANTI-infective agents , *ANIMAL experimentation , *FRIEDMAN test (Statistics) , *BRAIN injuries , *CEREBRAL ischemia , *CEREBRAL anoxia , *HIPPOCAMPUS (Brain) , *DATA analysis software , *COMPARATIVE studies , *CELLS , *INTERLEUKINS - Abstract
Objective Hydroxychloroquine (HCQ) has immunomodulatory, antithrombotic, cardiovascular, antimicrobial, and antineoplastic effects. In this study, we aimed to investigate the antiapoptotic and immunomodulator effects of intraperitoneal HCQ on hypoxic–ischemic (HI) injury in newborn rats. Study Design Wistar albino rats, 7 to 10 days old, were randomly divided into three groups: hypoxic–ischemic encephalopathy (HIE) group, HIE treated with HCQ group, and Sham group. Left common carotid artery ligation and hypoxia model were performed in HIE and HCQ groups. The HCQ group was treated with 80 mg/kg intraperitoneal HCQ every 24 hours for 3 days, while Sham and HIE groups were given physiological saline. After 72 hours, rats were decapitated and brain tissues were stained with hematoxylin and eosin, TUNEL, and IL-1β for histopathological grading and neuronal cell injury. Results Neuronal apoptosis was statistically lower in all neuroanatomical areas in the HCQ group compared with the HIE group. IL-1β-stained areas were similar in both HCQ and HIE groups but significantly higher compared with the Sham group. Histopathological grading scores were found to be lower in the HCQ group on the left parietal cortex and hippocampus region. Conclusion In this study, we have shown for the first time that HCQ treatment decreased apoptosis in HI newborn rat model in both hemispheres. HCQ may be a promising adjuvant therapy in neonatal HIE. Key Points HCQ decreased neuronal apoptosis in the ischemic penumbra of the rat brain. HCQ attenuates hypoxia–ischemia-induced brain injury in neonatal rats. HCQ has no anti-inflammatory effect on HI injury. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Exploring Neuroprotective Effects of Topical Brimonidine in Experimental Diabetic Retinopathy.
- Author
-
KYOUNG IN JUNG, JIE HYUN KIM, JEONG-SUN HAN, and CHAN KEE PARK
- Subjects
NEUROPROTECTIVE agents ,DIABETIC retinopathy treatment ,IMMUNOFLUORESCENCE ,MITOGEN-activated protein kinases ,RETINAL ganglion cells - Abstract
Background/Aim: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. Materials and Methods: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. Results: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho-protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in antiapoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). Conclusion: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Causal associations of antioxidants with Alzheimer's disease and cognitive function: a Mendelian randomisation study.
- Author
-
Jiao Wang, Yingyue Huang, Chunhua Bei, Huiling Yang, Zihong Lin, and Lin Xu
- Subjects
ALZHEIMER'S disease risk factors ,GENETICS of Alzheimer's disease ,RISK assessment ,NEUROPROTECTIVE agents ,RESEARCH funding ,GENOME-wide association studies ,VITAMIN C ,SELENIUM ,VITAMIN A ,ZINC ,DESCRIPTIVE statistics ,ODDS ratio ,BETA carotene ,ANTIOXIDANTS ,CONFIDENCE intervals ,REACTION time ,COGNITION ,SINGLE nucleotide polymorphisms - Published
- 2024
- Full Text
- View/download PDF
35. Efficient Two-Step Synthesis of Novel Pyrimido[4,5-d] Pyrimidines with Potent Neuroprotective, Antioxidant, and Aβ Anti-Aggregation Properties
- Author
-
Ghada Ben Ameur, Emna Maalej, Helene Martin, Anne-Sophie Jacquinot, Nadine Barbanneau, Paul J. Bernard, José Marco-Contelles, Fakher Chabchoub, and Lhassane Ismaili
- Subjects
Aβ1-42 self-aggregation inhibition ,antioxidant ,neuroprotective agents ,pyrimido [4,5-d] pyrimidines ,Chemistry ,QD1-999 - Abstract
Eleven new differently substituted N,7-diphenylpyrimido [4,5-d]pyrimidin-4-amines 4a–k were synthesized from readily available reagents in a simple and inexpensive two-step procedure with yields up to 57%. Neuroprotective analysis against H2O2 and analysis using ORAC assays identified compounds 4g, 4i and 4j as promising antioxidant compounds. These compounds also showed potent inhibition of Aβ1–42 self-aggregation, and suitable physicochemical properties predicted by Datawarior software V6.1.0, this biological activity and physicochemical property being of great interest for pathologies linked to oxidative stress, such as Alzheimer’s disease.
- Published
- 2024
- Full Text
- View/download PDF
36. Neuroprotective effects of Tradescantia spathacea tea bioactives in Parkinson’s disease: In vivo proof-of-concept
- Author
-
Lorenna E.S. Lopes, Sheilla da Silva Barroso, Joanny K.M. Caldas, Paulo R. Vasconcelos, Kirley M. Canuto, Claudio Dariva, Klebson S. Santos, Patricia Severino, Juliana C. Cardoso, Eliana B. Souto, and Margarete Z. Gomes
- Subjects
Neuroprotective agents ,Parkinson’s disease ,Preclinical evaluation ,Infusion ,Tradescantia ,Medicine - Abstract
Background and aim: Tradescantia spathacea (T. spathacea) is a traditional medicinal plant from Central America and its tea, obtained by infusion, has been recognized as a functional food. The aim of this work was to investigate the effects of dry tea containing biocompounds from T. spathacea tea on motor and emotional behavior, as well as tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression in 6-hydroxydopamine (6-OHDA)-lesioned rats. Experimental procedure: Bioactives were identified by Ultra Performance Liquid Chromatography (UPLC) and an in vivo study in male Wistar rats was run as proof of concept of neuroprotective effects of DTTS. Results and conclusion: We found 15 biocompounds that had not been previously reported in T. spathacea: the UPLC-QTOF-MS/MS allowed identification five phenolic acids, one coumarin, two flavonoids, one iridoid, one phenylpropanoid glycoside, and six fatty acid derivatives. The dry tea of T. spathacea (DTTS) presented significant antioxidant activity and high contents of phenolic compounds and flavonoids. Doses of 10, 30, and 100 mg/kg of DTTS were protective against dopaminergic neurodegeneration and exhibited modulatory action on the astrocyte-mediated neuroinflammatory response. Behavioral tests showed that 30 mg/kg of DTTS counteracted motor impairment, while 100 mg/kg produced an anxiolytic effect. The DTTS could be, therefore, a promising strategy for the management of Parkinson's disease.
- Published
- 2024
- Full Text
- View/download PDF
37. Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome — a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)
- Author
-
Engel, Corinna, Rüdiger, Mario, Benders, Manon J. N. L., van Bel, Frank, Allegaert, Karel, Naulaers, Gunnar, Bassler, Dirk, Klebermaß-Schrehof, Katrin, Vento, Maximo, Vilan, Ana, Falck, Mari, Mauro, Isabella, Metsäranta, Marjo, Vanhatalo, Sampsa, Mazela, Jan, Metsvaht, Tuuli, van der Vlught, Roselinda, Franz, Axel R., Poets, Christian F., and Guimarães, Hercilia
- Subjects
- *
NEUROPROTECTIVE agents , *BRAIN injuries , *ALLOPURINOL , *CEREBRAL anoxia-ischemia , *STATISTICS , *NEONATAL intensive care , *PERFUSION , *REPERFUSION - Abstract
Background: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and."will be stratified for the two treatment groups. Discussion: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Therapeutic Potential of Fingolimod on Psychological Symptoms and Cognitive Function in Neuropsychiatric and Neurological Disorders.
- Author
-
Rahmati-Dehkordi, Fatemeh, Khanifar, Hadi, Najari, Nazanin, Tamtaji, Zeinab, Talebi Taheri, Abdolkarim, Aschner, Michael, Shafiee Ardestani, Mehdi, Mirzaei, Hamed, Dadgostar, Ehsan, Nabavizadeh, Fatemeh, and Tamtaji, Omid Reza
- Subjects
- *
NEUROBEHAVIORAL disorders , *NEUROLOGICAL disorders , *NEUROPROTECTIVE agents , *NEURAL transmission , *MEMORY disorders - Abstract
Neuropsychiatric and neurological disorders pose a significant global health burden, highlighting the need for innovative therapeutic approaches. Fingolimod (FTY720), a common drug to treat multiple sclerosis, has shown promising efficacy against various neuropsychiatric and neurological disorders. Fingolimod exerts its neuroprotective effects by targeting multiple cellular and molecular processes, such as apoptosis, oxidative stress, neuroinflammation, and autophagy. By modulating Sphingosine-1-Phosphate Receptor activity, a key regulator of immune cell trafficking and neuronal function, it also affects synaptic activity and strengthens memory formation. In the hippocampus, fingolimod decreases glutamate levels and increases GABA levels, suggesting a potential role in modulating synaptic transmission and neuronal excitability. Taken together, fingolimod has emerged as a promising neuroprotective agent for neuropsychiatric and neurological disorders. Its broad spectrum of cellular and molecular effects, including the modulation of apoptosis, oxidative stress, neuroinflammation, autophagy, and synaptic plasticity, provides a comprehensive therapeutic approach for these debilitating conditions. Further research is warranted to fully elucidate the mechanisms of action of fingolimod and optimize its use in the treatment of neuropsychiatric and neurological disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Synthesis of a collection of nootkatone analogues with diverse skeletons.
- Author
-
Zhang, Yu-Ting, Guo, Jing, Zhao, Yu, and Si, Chao
- Subjects
- *
ORGANIC compound analysis , *ANTI-inflammatory agents , *NEUROPROTECTIVE agents , *PHENOMENOLOGICAL biology , *TERPENES , *ANTINEOPLASTIC agents , *GRAPEFRUIT , *BIOLOGICAL products , *BIOCHEMISTRY , *PLANT extracts , *INSECTICIDES , *MOLECULAR structure , *ANTIOXIDANTS , *MEDICINAL plants , *ANALYTICAL chemistry , *PHARMACODYNAMICS - Abstract
A collection of ring distorted analogue of Nootkatone including 6 CTD (Complex to Diversity) compounds and 9 SAR (Structure Activity Relationship) compounds were synthesized utilizing the carbonyl group as a starting reaction point. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models.
- Author
-
Abady, Mariam M., Ji-Seon Jeong, Ha-Jeong Kwon, Assiri, Abdullah M., Jongki Cho, and Saadeldin, Islam M.
- Subjects
NEUROPROTECTIVE agents ,ANIMAL models in research ,DRUG utilization ,GENITALIA ,REPRODUCTIVE health - Abstract
The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic druginduced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Stress-relieving properties of a polyherbal blend with <italic>Syzygium aromaticum</italic> L. and <italic>Coffea canephora</italic> Pierre ex A. Froehner: A review and bibliometric analysis.
- Author
-
Zakaria, Nor Hafizah, Fadhlina, Anis, Sheikh, Hassan Ibrahim, Hairani, Muhammad Afnan Syakir, Mohd Fauzi, Mohd Syabil Haiman, and Abdul Majid, Fadzilah Adibah
- Subjects
- *
BIBLIOMETRICS , *PLANT extracts , *SOFTWARE measurement , *CHLOROGENIC acid , *HERBAL teas , *OXIDATIVE stress , *SEROTONIN , *NEUROPROTECTIVE agents - Abstract
AbstractObjectiveMethodsResultsConclusions
Syzygium aromaticum andCoffea canephora are acknowledged for their outstanding antioxidant, anti-inflammatory, and nerve-stimulant properties, showcasing potential in brain protection. Therefore, this study aims to quantitatively review existing literature and assess the potential of using it to formulate a herbal tea blend for managing stress and anxiety.Data was retrieved from the Scopus database, and a bibliometric analysis was performed using VOSviewer software.Following a screening process, a total of 121 articles were identified, withS. aromaticum yielding a higher number compared toC. canephora . A detailed exploration of each plant revealed active components such as eugenol, β-caryophyllene, α-humulene, caffeine, mangiferin, and chlorogenic acids, each exhibiting stimulatory effects alongside antioxidant and anti-inflammatory properties. The neuroprotective effects were attributed to the reduction of oxidative stress and inflammation, coupled with the stimulation of neurotransmitters and hormones like dopamine, serotonin, cortisol, and adrenaline.The review showed that these plants positively affect mood and cognition by influencing the brain’s pleasure system. This suggests the need for further research to combine these plant extracts for developing ‘Tenang tea’, a potential herbal blend for managing stress and anxiety. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
42. Therapeutic effects of a novel synthetic α-secretase.
- Author
-
Sung Bin Kim, Bo-Ram Mun, Sung Yoon Kim, Elangovan, Muthukumar, Euy Jun Park, Won-Seok Choi, and Woo Jin Park
- Subjects
PROTEIN precursors ,NEUROPROTECTIVE agents ,ALZHEIMER'S disease ,RESEARCH funding ,ANIMALS ,POLYMERASE chain reaction ,DESCRIPTIVE statistics ,GENE expression ,MICE ,CELL lines ,EXPERIMENTAL design ,IMMUNOHISTOCHEMISTRY ,ANIMAL experimentation ,WESTERN immunoblotting ,ONE-way analysis of variance ,COGNITION ,MEMBRANE proteins ,PHARMACODYNAMICS - Abstract
Excessive accumulation of amyloid-β (Aβ) has been associated with the pathogenesis of Alzheimer’s disease (AD). Clinical studies have further proven that elimination of Aβ can be a viable therapeutic option. In the current study, we conceptualized a fusion membrane protein, referred to as synthetic α-secretase (SAS), that can cleave amyloid precursor protein (APP) and Aβ specifically at the α-site. In mammalian cells, SAS indeed cleaved APP and Aβ at the α-site. Overexpression of SAS in the hippocampus was achieved by direct injection of recombinant adeno-associated virus serotype 9 (AAV9) that expresses SAS (AAV9-SAS) into the bilateral ventricles of mouse brains. SAS enhanced the non-amyloidogenic processing of APP, thus reducing the levels of soluble Aβ and plaques in the 5xFAD mice. In addition, SAS significantly attenuated the cognitive deficits in 5xFAD mice, as demonstrated by novel object recognition and Morris water maze tests. Unlike other Aβ-cleaving proteases, SAS has highly strict substrate specificity. We propose that SAS can be an efficient modality to eliminate excessive Aβ from diseased brains. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. IGF-1 Mediated Neuroprotective Effects of Olfactory-Derived Mesenchymal Stem Cells on Auditory Hair Cells.
- Author
-
Lammers, Marc J. W., Young, Emily, Yanai, Anat, Viringipurampeer, Ishaq A., Le, Trung N., Straatman, Louise V., Westerberg, Brian D., and Gregory-Evans, Kevin
- Subjects
- *
NEUROPROTECTIVE agents , *ADIPOSE tissues , *SURVIVAL rate , *RESEARCH funding , *MESENCHYMAL stem cells , *ENZYME-linked immunosorbent assay , *RATS , *CELL lines , *ANIMAL experimentation , *GROWTH factors , *SMELL disorders , *COMPARATIVE studies , *STEM cells , *HAIR cells - Abstract
Importance: Mesenchymal stem cells (MSCs) have the capability of providing ongoing paracrine support to degenerating tissues. Since MSCs can be extracted from a broad range of tissues, their specific surface marker profiles and growth factor secretions can be different. We hypothesized that MSCs derived from different sources might also have different neuroprotective potential. Objective: In this study, we extracted MSCs from rodent olfactory mucosa and compared their neuroprotective effects on auditory hair cell survival with MSCs extracted from rodent adipose tissue. Methods: Organ of Corti explants were dissected from 41 cochlea and incubated with olfactory mesenchymal stem cells (OMSCs) and adipose mesenchymal stem cells (AMSCs). After 72 hours, Corti explants were fixed, stained, and hair cells counted. Growth factor concentrations were determined in the supernatant and cell lysate using Enzyme-Linked Immunosorbent Assay (ELISA). Results: Co-culturing of organ of Corti explants with OMSCs resulted in a significant increase in inner and outer hair cell stereocilia survival, compared to control. Comparisons between both stem cell lines, showed that co-culturing with OMSCs resulted in superior inner and outer hair cell stereocilia survival rates over co-culturing with AMSCs. Assessment of growth factor secretions revealed that the OMSCs secrete significant amounts of insulin-like growth factor 1 (IGF-1). Co-culturing OMSCs with organ of Corti explants resulted in a 10-fold increase in IGF-1 level compared to control, and their secretion was 2 to 3 times higher compared to the AMSCs. Conclusions: This study has shown that OMSCs may mitigate auditory hair cell stereocilia degeneration. Their neuroprotective effects may, at least partially, be ascribed to their enhanced IGF-1 secretory abilities compared to AMSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Investigating the potential neuroprotective benefits of taurine and Dihydrotestosterone and Hydroxyprogesterone levels in SH-SY5Y cells.
- Author
-
Almohaimeed, Hailah M., Almars, Amany I., Alsulaimani, Fayez, Basri, Ahmed M., Althobaiti, Norah A., Albalaw, Aishah E., Alsharif, Ifat, Al Abdulmonem, Waleed, Hershan, Almonther Abdullah, and Soliman, Mona H.
- Subjects
RNA metabolism ,THERAPEUTIC use of testosterone ,PROGESTERONE ,NEUROPROTECTIVE agents ,ALZHEIMER'S disease ,DATA analysis ,RESEARCH funding ,ENZYME-linked immunosorbent assay ,POLYMERASE chain reaction ,DESCRIPTIVE statistics ,CELL lines ,GENE expression ,CYTOTOXINS ,AGING ,STATISTICS ,ANALYSIS of variance ,DATA analysis software ,ALKANES ,PHARMACODYNAMICS - Abstract
Background: Taurine, an amino acid abundantly found in the brain and other tissues, has potential neuroprotective properties. Alzheimer's disease (AD) is a commonly occurring type of dementia, which becomes more prevalent as people age. This experiment aimed to assess the neuroprotective effects of taurine on SH-SY5Y cells by examining its impact on Dihydrotestosterone (DHT), Dihydroprogesterone (DHP), as well as the expression of miRNA-21 and miRNA-181. Methods: The effects of various taurine concentrations (0.25, and 0.75 mg/mL), and LPS (0.1, and 12 mg/mL) on the SH-SY5Y cell line were assessed using the MTT assay. The levels of DHT and DHP were quantified using an ELISA kit. Additionally, the expression levels of miRNA-181 and miRNA-21 genes were examined through Real-Time PCR analysis. Results: The results of the MTT assay showed that treatment with taurine at concentrations of 0.25, and 0.75 mg/mL reduces the toxicity of LPS in SHSY5Y cells. ELISA results indicated that taurine at a concentration of 0.25, and 0.75 mg/mL significantly elevated DHT and DHP hormones in the SH-SY5Y cell line compared to the untreated group (p < 0.01). The expression levels of IL-1β and IL-6 were decreased under the influence of LPS in SH-SY5Y cells after taurine treatment (p < 0.01). Gene expression analysis revealed that increasing taurine concentration resulted in heightened expression of miRNA-181 and miRNA-21, with the most significant increase observed at a concentration of 0.75 mg/mL (p < 0.001). Conclusion: Our study findings revealed that the expression of miRNA-181 and miRNA-21 can be enhanced by taurine. Consequently, exploring the targeting of taurine, miRNA-181, and miRNA-21 or considering hormone therapy may offer potential therapeutic approaches for treating AD or alleviating severe symptoms. Nonetheless, in order to fully comprehend the precise mechanisms involved, additional research is required. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Edaravone dexborneol attenuates oxidative stress in experimental subarachnoid hemorrhage via Keap1/Nrf2 signaling pathway.
- Author
-
Kunyuan Zhu, Shijun Bi, Zechao Zhu, Wenxu Zhang, Xinyu Yang, Jiashuo Li, Guobiao Liang, Chunyong Yu, and Pengyu Pan
- Subjects
SUBARACHNOID hemorrhage ,CELLULAR signal transduction ,EDARAVONE ,ISCHEMIC stroke ,NEUROPROTECTIVE agents ,OXIDATIVE stress - Abstract
Background: Subarachnoid hemorrhage (SAH) serves as a disease characterized by high incidence rate, which is exceedingly prevalent and severe. Presently, there is no unambiguous or efficacious intervention for the neurological impairment following SAH. Administering multi-targeted neuroprotective agents to reduce oxidative stress (OS) and neuroinflammation caused by early brain injury (EBI) has been demonstrated to improve neurological function and prognosis following SAH. Edaravone dexborneol (EDB), a novel multi targeted neuroprotective medication, combines four parts edaravone (EDA) with 1 part (+)-borneol in proportion. Clinical trials conducted in China have revealed during 2 days of acute ischemic stroke (AIS), early administration of EDB leads to improved therapeutic outcomes compared to treatment in EDA monotherapy. Currently, there is no clear evidence that EDB can effectively treat SAH, therefore, our study aims to investigate its potential therapeutic effects and mechanisms on EBI after SAH. Method: We used the intravascular threading method to establish a mouse model of SAH to explore whether EDA and EDB could produce anti-OS and antiapoptosis effects. Behavioral assessment of mice was conducted using the balance beam experiment and the modified Garcia scoring system. Neuronal damage due to OS and Keap1/Nrf2 signaling pathway were detected through techniques of immunofluorescence, Western blotting, spectrophotometry. The group of EDA and EDB were injected intraperitoneally for 72 h after SAH. Results: The experiment results indicated that EDB lead to remarkably positive results by significantly enhancing neurological function, reducing blood-brain barrier (BBB) injury, and effectively inhibiting neuronal apoptosis after SAH. Further examination indicated EDB significantly reduced the expression of Keap1 and increased the expression of Nrf2, and it inhibited MDA, and enhanced SOD activity after SAH. These outcomes surpassed the effectiveness observed in EDA monotherapy. However, the application of ML385 reversed the anti-OS effects of EDB and EDA. Conclusion: Our experimental findings indicated that EDB could activate Keap1/Nrf2 signaling pathway to reduce OS damage, thereby protecting neurological function and enhancing behavioral abilities after SAH. These outcomes could facilitate the creation of new approaches for the clinical management of SAH. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Experimental verification about treatment of Bu-Shen-Yi-Jing-Fang in Alzheimer's disease by the analysis of the feasible signaling pathway of network pharmacology.
- Author
-
Hu, Yingchao, Hao, Renjuan, Li, Deyu, Lu, Yunwei, and Yu, Guran
- Subjects
CHINESE medicine ,NEUROPROTECTIVE agents ,IN vitro studies ,FLOW cytometry ,COMPUTER-assisted molecular modeling ,ALZHEIMER'S disease ,PROTEIN kinases ,DATA analysis ,RESEARCH funding ,HERBAL medicine ,PHARMACEUTICAL chemistry ,APOPTOSIS ,OXIDATIVE stress ,CELLULAR signal transduction ,NEUROECTODERMAL tumors ,FLUORESCENT antibody technique ,DESCRIPTIVE statistics ,CELL lines ,CELL culture ,REACTIVE oxygen species ,ANTIOXIDANTS ,CELL death ,WESTERN immunoblotting ,MASS spectrometry ,ONE-way analysis of variance ,STATISTICS ,TRANSFERASES ,DATA analysis software ,AMYLOID beta-protein precursor ,NUCLEAR factor E2 related factor ,PHARMACODYNAMICS - Abstract
Context: Bu-shen-yi-jing-fang (BSYJF) has been reported to reduce amyloid-β (Aβ)
1–42 deposition in the brain of APP/PS1 mice and ameliorate cognitive function. However, its neuroprotective mechanism remains unclear. Objective: This study aims to investigate whether BSYJF exerts a protective effect on Aβ1–42 -induced oxidative stress injury and explore its possible mechanism. Materials and methods: The platform databases TCMSP, Swiss, TTD, DrugBank, and GeneCards were used to mine the targets of Alzheimer's disease (AD) and BSYJF. The platform databases STRING and Metascape were used to build the interaction network of the target protein, and Cytoscape software was used to analyze this network and screen out the key pathways. Aβ1–42 -treated SKNMC cells were established to verify the mechanism of BSYJF and the key proteins. The downstream proteins and antioxidants as well as apoptosis and ferroptosis of the PI3K/AKT/Nrf2 signaling pathway were validated using an in vitro SKNMC cell model experiment. The expression levels of related proteins were detected using Western blotting. Flow cytometry and immunofluorescence staining were used to analyze apoptosis and ferroptosis. Results: Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis considered the key signal pathways, mainly involving the PI3K/AKT signaling pathway. Experimental validation demonstrated that BSYJF treatment markedly increased the activity of the PI3K/AKT pathway, which could exert anti-AD effects. Conclusions: Our data provided compelling evidence that the protective effects of BSYJF might be associated with their regulation of the PI3K/AKT/Nrf2 signaling pathway. These studies offered a potential therapy for natural herbal medicine treatment of AD. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
47. A Double-Blinded Placebo-Controlled Randomized Trial with or without Memantine for the Prevention of Radiation-Induced Cognitive Dysfunction in Brain Metastatic Patients—CTRI/2022/01/039599: An Interim Analysis.
- Author
-
Surendran, Haripriya, Kavalagunta, Sruthi, Parasuraman, Ayiramuthu, Narmadha, Poornachary Mukunthu, Mangalath, Sabitha, Chandran, Dhanya, Sasidharan, Ajay, and Dutta, Debnarayan
- Subjects
- *
COGNITION disorders , *MEMANTINE , *METASTASIS , *STEREOTACTIC radiosurgery , *NEUROPROTECTIVE agents - Abstract
This article presents the findings of a double-blinded placebo-controlled randomized trial investigating the efficacy of memantine as a cognitive function protective agent for brain metastatic patients undergoing radiation therapy. The study included adult patients with brain metastases who were randomized to receive either placebo or memantine for 6 months. Cognitive scores were assessed at baseline, 16 weeks, and 24 weeks. The interim analysis showed that the memantine arm had statistically significant cognitive preservation in brain metastatic patients receiving stereotactic radiosurgery. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
48. Early Intravenous Magnesium Sulfate and Its Impact on Cerebral Vasospasm as well as Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Retrospective Matched Case-Control Analysis.
- Author
-
Feulner, Julian, Weidinger, Cornelia S., Dörfler, Arnd, Birkholz, Torsten, Buchfelder, Michael, and Sommer, Björn
- Subjects
- *
CEREBRAL vasospasm , *CEREBRAL ischemia , *SUBARACHNOID hemorrhage , *MAGNESIUM sulfate , *NEUROPROTECTIVE agents - Abstract
Magnesium sulfate (MgSO 4) is a potential neuroprotective agent for patients with aneurysmal subarachnoid hemorrhage (SAH). We analyzed the effect of early application of intraoperative intravenous MgSO 4 and compared cerebral vasospasm (CV), delayed cerebral ischemia (DCI), and neurological outcome in 2 patient cohorts. A retrospective matched-pair analysis from patients at a single center in Germany was performed without (group A) and with (group B) MgSO 4 application <24 hours after diagnosis. Pairs were matched according to the known risk factors for DCI and CV (age, Fisher grade, smoking, severity of SAH). Incidence of CV and DCI and neurological outcome using the modified Rankin Scale score 3 and 12 months after SAH were recorded. The inclusion criteria were met by 196 patients. After risk stratification, 48 patients were included in the final analysis (age 54.2 ± 8.1 years; 30 women and 18 men) and were assigned to group A (n = 24) or group B (n = 24). CV occurred less frequently in group B (33%) than in group A (46%). Likewise, DCI was present in 13% in group B compared with 42% in group A. After 12 months, 22 patients in group B had a favorable functional outcome (modified Rankin Scale score 0–3) compared with 15 patients in group A. In this study, the incidence of CV and DCI was lower in patients receiving intravenous MgSO 4 within 24 hours after aneurysmal SAH onset. Favorable functional outcome was more likely in the MgSO 4 group after 12 months of follow-up. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. MAO-B Inhibitor (2E)-3-(4-Bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one as a Neuroprotective Agent Against Alzheimer's Disease.
- Author
-
Sasidharan, Rani, Mohanan, Ratheesh, Kukreti, Neelima, Raj, Praveen, Abdelgawad, Mohamed A., Ghoneim, Mohammed M., Manju, Sreedharannair L., and Mathew, Bijo
- Subjects
- *
ALZHEIMER'S disease , *NEUROPROTECTIVE agents , *ACETYLCHOLINESTERASE , *MONOAMINE oxidase inhibitors , *CHALCONES , *CARBONYL group , *SECRETASE inhibitors - Abstract
Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, β-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer's disease (AD). Based on our previous research, 11 indolyl chalcones (IC1–IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. Orientin Modulates Nrf2-ARE, PI3K/Akt, JNK-ERK1/2, and TLR4/NF-kB Pathways to Produce Neuroprotective Benefits in Parkinson's Disease.
- Author
-
Vasudevan Sajini, Deepak, Thaggikuppe Krishnamurthy, Praveen, Chakkittukandiyil, Amritha, and Mudavath, Ravi Naik
- Subjects
- *
PARKINSON'S disease , *MUSCLE rigidity , *MEMBRANE potential , *REACTIVE oxygen species , *GLUTATHIONE peroxidase , *NEUROPROTECTIVE agents , *CATALASE , *EXTRACELLULAR signal-regulated kinases - Abstract
Parkinson's disease (PD) is characterized by oxidative stress and neuroinflammation as key pathological features. Emerging evidence suggests that nuclear factor erythroid 2 related factor 2-antioxidant response element (Nrf2-ARE), phosphatidylinositol 3‑kinase-protein kinase B (PI3K-Akt), c-Jun N-terminal kinase-extracellular signal-regulated kinase 1/2 (JNK-ERK1/2), and toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kB) pathways play pivotal roles in PD pathogenesis. Orientin, a phenolic phytoconstituent, has demonstrated modulatory potential on these pathways in various experimental conditions other than PD. In this study, we aimed to evaluate the neuroprotective effects of Orientin against rotenone-induced neurodegeneration in SH-SY5Y cell lines and the Swiss albino mice model of PD. Orientin was administered at doses 10 and 20 µM in cell lines and 10 and 20 mg/kg in mice, and its effects on rotenone-induced neurodegeneration were investigated. Oxidative stress markers including mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as inflammatory markers including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were measured. The expression levels of genes related to Nrf2-ARE (Nrf2), PI3K/Akt (Akt), JNK-ERK1/2 (TNF-α), and TLR4/NF-kB (TNF-α) pathways were measured to understand the modulatory effect of Orientin on these pathways. Additionally, behavioral studies assessing locomotor activity, muscle coordination, and muscle rigidity were conducted with mice. Our results indicate that Orientin dose-dependently attenuated rotenone-induced changes in oxidative stress markers, inflammatory markers, gene expression levels, and behavioral parameters. Therefore, our study concludes that Orientin exhibits significant neuroprotective benefits against rotenone-induced PD by modulating Nrf2-ARE, PI3K-Akt, JNK-ERK1/2, and TLR4/NF-kB pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.