Neuroprotective Medicine Research Articles

Enhancements in Parkinson's Disease Management: Leveraging Levodopa Optimization and Surgical Breakthroughs.

Parkinson's disease (PD) is a complex neurological condition caused due to inheritance, environment, and behavior among various other parameters. The onset, diagnosis, course of therapy, and future of PD are thoroughly examined in this comprehensive review. This review also insights into pathogenic mechanisms of reactive microgliosis, Lewy bodies, and their functions in the evolution of PD. It addresses interaction complexity with genetic mutations, especially in genes such as UCH-L1, parkin, and α-synuclein, which illuminates changes in the manner dopaminergic cells handle proteins and use proteases. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy. This raises the improved outcomes and life quality for those with PD. Potential treatments for severe PD include new surgical methods like Deep Brain Stimulation (DBS). Further, exploration of non-motor manifestations, such as cognitive impairment, autonomic dysfunction, and others, is covered in this review article. These symptoms have a significant impact on patients' quality of life. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy.

Therapeutic Potential of Natural Flavonoids: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective on Parkinson's Disease

Abstract: Parkinson’s disease (PD) is a prominent area of study within the field of neurology, particularly neurodegenerative disease (ND). The peak incidence of PD occurs in those over the age of 45, and the disease’s prevalence rises continuously with age, the incidence of PD has skyrocketed over the world. A slow decline in neural function characterizes NDs, but the pathophysiological mechanisms behind this decline remain elusive. Because the pathophysiological mechanisms behind neurodegeneration are intricate, the clinical issue of finding efficient, multi-target treatments still exists. Furthermore, adequate neuroprotective medicines are currently scarce, necessitating the development of new therapeutic agents. There is currently no medicine for PD that is without side effects. The ability of natural flavonoids to lower the risk of PD has contributed to an increase in their popularity in recent years, models both in vivo and in vitro. Flavonoids are multi-target natural substances that affect distinct pathogenic pathways in neurodegeneration. As a result, the emphasis has turned to discovering natural product inhibitors for the treatment of PD. The majority of the results pointed to flavonoids' beneficial role in the treatment of PD and no adverse events were reported. This review offered scientific data on the protective and preventative functions of flavonoids. It has been demonstrated that flavonoids have a neuroprotective effect by activating anti-apoptotic mechanisms that target mitochondrial dysfunction and produce neurotrophic factors. In addition to having antioxidant, anti-inflammatory, and protective dopaminergic neurons. Even though no evidence using flavonoids as a treatment might reverse the abnormal phenotypes of PD patients, it was also indicated that flavonoids might be promising natural remedies for PD prevention and could be used as therapeutic agents against PD.

Late onset psychosis treatment with adjunctive medicines.

A number of studies have shown the feasibility of using adjunctive drugs in late onset psychosis (LOP). Testing hypothesis that among LOP people treated with antipsychotics and antidepressants, basing on certain clinical characteristics a subgroup of patients might be distinguished, for whom adjunctive therapy is advantageous. This subgroup might be identified by measurement of blood biochemical parameters. 59 in-patients with LOP, treated neuroleptics and antidepressants, were included, and followed in real clinical practice. Database containing demographic, clinical data (scores by PANSS, CDSS, CGI-S, HAMD-17), prescribed therapy, adverse effects of antipsychotic and antidepressant treatment, and blood biochemical parameters (enzymatic activities of glutamate- and glutathione metabolism enzymes in platelets and erythrocytes) at baseline and after the treatment course was created. Three groups of patients (Gr1, Gr2, and Gr3), based on the adjunctive therapy usage were identified: Gr1 (n = 16) was without adjunctive therapy, two other groups (Gr2 and Gr3) were with adjunctive medicines, such as 2-ethyl-6-methyl-3-hydroxypyridine succinate (EMHS; Gr2, n = 20), or other drugs, such as citicoline, cerebrolysin, cortexin, actovegin, gliatilin (choline alfoscerate; Gr3, n = 23). The enzymatic activities were assessed also in the matched control group (n = 38). In all three patient groups, as compared with controls, activity of erythrocyte glutathione reductase was decreased at baseline and after the treatment course. In Gr2, unlike Gr1 or Gr3, there was a significant decrease in baseline glutamate dehydrogenase and glutathione-S-transferase activities. Certain clinical criteria were also elucidated for prescription of EMHS as adjunctive therapy for patients of Gr2. Glutamate dehydrogenase and glutathione-S-transferase activities returned closer to control levels after the treatment course in Gr2, unlike Gr1, where they declined yet more after psychotropic treatment without adjunctive medicine. Different significant links between biochemical parameters and scores by clinical scales were observed in Gr1, Gr2, and Gr3, some having predictive value for evaluation of antipsychotic treatment efficacy. We demonstrate the validity of adjunctive neuroprotective medicines' usage in addition to antipsychotic and antidepressant therapy in distinct subgroups of patients suffering with LOP, especially those who have prominent side effects accompanying their psychotropic treatment. Returning of biochemical parameters to control range following the treatment course observed in patients of the subgroup treated with adjunctive EMHS is evidence for their metabolism normalization.

Refined Qingkailing protects the in vitro neurovascular unit against oxygen–glucose deprivation and re-oxygenation-induced injury

Since the proposal of the neurovascular unit (NVU) theory, it has become almost mandatory for neuroprotective medicines against ischaemic stroke (IS) to focus on this unit. Refined Qingkailing (RQKL) is a compound composed of hyodeoxycholic acid, geniposide, baicalin and cholic acid, which has shown great potential in the treatment of IS, but its effect on NVU has not been fully studied. The purpose of this study was to investigate the potential biological pathways that underlie the protective effects of RQKL against NVU damage induced by oxygen–glucose deprivation and re-oxygenation (OGD/R). Using in vitro OGD/R models, we looked into whether RQKL protects the NVU. In order to create an in vitro NVU that resembles IS, we created an OGD/R injury model using primary cultures of brain microvascular endothelial cells, neurons, and astrocytes. Based on our results, we present evidence, for the first time, that RQKL treatment of the injury caused by OGD/R significantly (1) kept the blood brain barrier (BBB) functioning and maintained the architecture of the neurons, (2) mitigated the oxidative stress damage, inflammatory cytokine release, and neuronal death, and (3) upregulated the expression of neurotrophic factors generated from glial cells and the brain in the in vitro model. Therefore, RQKL has a variety of preventive effects against NVU damage caused by OGD/R. RQKL may be a suitable medication for treating IS in a clinical setting.

Exploring the Pharmacological Potential of Pyrazole Derivatives: A Comprehensive Review of Diverse Biological Activities

The different biological actions connected to pyrazole molecules are summarised in this review. The review emphasizes their potential as antimicrobial [1], anti-TMV analgesic [2], ACE inhibitor [3], anti-amoebic [5], and neuroprotective medicines [6]. The ability of pyrazole derivatives to modify particular enzymes, receptors, and pathways involved in a variety of illnesses and physiological processes has been thoroughly researched. Because of their adaptability in interacting with a variety of biological targets, pyrazole-based compounds are intriguing candidates for the creation of innovative medicines and agrochemicals. The synthesis and characterization of pyrazole derivatives are still being studied, and this work has the potential to lead to the development of novel therapeutics with applications in a variety of medical specialties. Key Words: Pyrazole, Biological Activity.

Anti-cholinesterase, anti-inflammatory and antioxidant properties of Combretum micranthum G. Don: Potential implications in neurodegenerative disease.

Brain damage is a severe and common pathology that leads to life-threatening diseases. Despite development in the research, the medical evidence of the effectiveness of potential neuroprotective medicines is insufficient. As a result, there is an immense and urgent demand for promising medication. For millennia, herbal remedies were a fundamental aspect of medical treatments. Combretum micranthum (CM), a plant of the family Combretaceae in sub-Saharan Africa, has been utilized in folklore medicine to cure diverse human ailments. In order to develop a neuroprotective phytomedicine, the current research was undertaken to explore the antioxidant, anti-inflammatory, anticholinesterase and neuroprotective potential of CM extract. Colorimetric methods were used to determine CM antioxidant activity, in-vitro protein denaturation and membrane destabilization assays were used to evaluate its anti-inflammatory capacity, anticholinesterase activity was carried out using Ellman's method, and neuroprotective potential was assessed on brain homogenate stressed with ferric chloride and ascorbic acid (FeCl2-AA) by assessing the lipoperoxidation biomarker malondialdehyde (MDA). In Ferric Reducing Antioxidant Power (IC50 = 27.15±0.06µg/mL) and Total Antioxidant Capacity (IC50 = 31.13±0.02µg/mL), CM extract demonstrated strong antioxidant activity. Anti-inflammatory effect were improved in heat-induced Egg albumin and BSA denaturation (IC 50 = 46.35±1.53 and 23.94±1.10µg/mL) as well as heat and hypotonia induced membrane destabilization (IC 50 = 20.96±0.11 and 16.75±0.94µg/mL).CM extract showed strong anticholinesterase activity (IC 50 = 59.85±0.91µg/mL). In an ex-vivo neuroprotective model, CM extract showed substantial inhibition (p<0.001) of oxidative damage caused by FeCl2-AA in brain tissue. C. micranthum may be a good candidate for its probable neuroprotective potential. Its neuroprotective benefits might be attributed to its antioxidant, anti-inflammatory and anticholinesterase effects.

Role of integrating cannabinoids and the endocannabinoid system in neonatal hypoxic-ischaemic encephalopathy.

Neonatal hypoxic-ischaemic events, which can result in long-term neurological impairments or even cell death, are among the most significant causes of brain injury during neurodevelopment. The complexity of neonatal hypoxic-ischaemic pathophysiology and cellular pathways make it difficult to treat brain damage; hence, the development of new neuroprotective medicines is of great interest. Recently, numerous neuroprotective medicines have been developed to treat brain injuries and improve long-term outcomes based on comprehensive knowledge of the mechanisms that underlie neuronal plasticity following hypoxic-ischaemic brain injury. In this context, understanding of the medicinal potential of cannabinoids and the endocannabinoid system has recently increased. The endocannabinoid system plays a vital neuromodulatory role in numerous brain regions, ensuring appropriate control of neuronal activity. Its natural neuroprotection against adult brain injury or acute brain injury also clearly demonstrate the role of endocannabinoid signalling in modulating neuronal activity in the adult brain. The goal of this review is to examine how cannabinoid-derived compounds can be used to treat neonatal hypoxic-ischaemic brain injury and to assess the critical function of the endocannabinoid system and its potential for use as a new neuroprotective treatment for neonatal hypoxic-ischaemic brain injury.

Oleuropein confers neuroprotection against rotenone-induced model of Parkinson’s disease via BDNF/CREB/Akt pathway

Major pathological features of Parkinson’s disease (PD) include increase in oxidative stress leading to the aggregation of α-synuclein, mitochondrial dysfunction and apoptosis of dopaminergic neurons. In addition, downregulation of the expression of neurotrophic factors like-Brain Derived Neurotrophic Factor (BDNF) is also involved in PD progression. There has been a lot of interest in trophic factor-based neuroprotective medicines over the past few decades to treat PD symptoms. Rotenone, an insecticide, inhibits the mitochondrial complex I causing overproduction of ROS, oxidative stress, and aggregation of α-synuclein. It has been shown that BDNF and Tropomyosin receptor kinase B (TrkB) interaction initiates the regulation of neuronal cell development and differentiation by the serine/threonine protein kinases like Akt and GSK-3β. Additionally, Transcription factor CREB (cAMP Response Element-binding protein) also determines the gene expression of BDNF. The homeostasis of these signalling cascades is compromised with the progression of PD. Therefore, maintaining the equilibrium of these signalling cascades will delay the onset of PD. Oleuropein (OLE), a polyphenolic compound present in olive leaves has been documented to cross blood brain barrier and shows potent antioxidative property. In the present study, the dose of 8, 16 and 32 mg/kg body weight (bwt) OLE was taken for dose standardisation. The optimised doses of 16 and 32 mg/kg bwt was found to be neuroprotective in Rotenone induced PD mouse model. OLE improves motor impairment and upregulate CREB regulation along with phosphorylation of Akt and GSK-3β in PD mouse. In addition, OLE also reduces the mitochondrial dysfunction by activation of enzyme complexes and downregulates the proapoptotic markers in Rotenone intoxicated mouse model. Overall, our study suggests that OLE may be used as a therapeutic agent for treatment of PD by regulating BDNF/CREB/Akt signalling pathway.

Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes' lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin's mechanism of action as a neuroprotective medicine in the future.

An overview on diagnosis and prevention of ischaemic stroke

Acute ischemic stroke is a significant public health concern that will become more important to neurologists in the future. Timely reperfusion therapy remains the cornerstone of successful stroke management. This necessitates public and first responder identification of symptoms early on, triage to a suitable stroke center, and rapid evaluation and investigation by the attending stroke team. In properly chosen patients, intravenous thrombolysis and/or endovascular thrombectomy are used to accomplish recanalisation and reperfusion of the ischemic penumbra. All patients should be admitted to an acute stroke unit for careful monitoring to avoid subsequent problems and early neurological impairment. Patients may begin appropriate secondary preventive therapy as soon as the mechanism of stroke is identified. Future goals include making endovascular thrombectomy more accessible, extending treatment windows with improved imaging, and finding neuroprotective medicines to avoid subsequent neuronal injury.

Metabolic engineering of Saccharomyces cerevisiae for high-level production of gastrodin from glucose

BackgroundThe natural phenolic glycoside gastrodin is the major bioactive ingredient in the well-known Chinese herb Tianma and is widely used as a neuroprotective medicine in the clinic. Microbial production from sustainable resources is a promising method to replace plant extraction and chemical synthesis which were currently used in industrial gastrodin production. Saccharomyces cerevisiae is considered as an attractive host to produce natural plant products used in the food and pharmaceutical fields. In this work, we intended to explore the potential of S. cerevisiae as the host for high-level production of gastrodin from glucose.ResultsHere, we first identified the plant-derived glucosyltransferase AsUGT to convert 4-hydroxybenzyl alcohol to gastrodin with high catalytic efficiency in yeast. Then, we engineered de novo production of gastrodin by overexpressing codon-optimized AsUGTsyn, the carboxylic acid reductase gene CARsyn from Nocardia species, the phosphopantetheinyl transferase gene PPTcg-1syn from Corynebacterium glutamicum, the chorismate pyruvate-lyase gene UbiCsyn from Escherichia coli, and the mutant ARO4K229L. Finally, we achieved an improved product titer by a chromosomal multiple-copy integration strategy and enhancement of metabolic flux toward the aglycon 4-hydroxybenzyl alcohol. The best optimized strain produced 2.1 g/L gastrodin in mineral medium with glucose as the sole carbon source by flask fermentation, which was 175 times higher than that of the original gastrodin-producing strain.ConclusionsThe de novo high-level production of gastrodin was first achieved. Instead of chemical synthesis or plants extraction, our work provides an alternative strategy for the industrial production of gastrodin by microbial fermentation from a sustainable resource.

Development of the Composition and Technology of New Neuroprotective Drug Tablets Using Fractional Factorial Design

Introduction. The creating an effective and safe domestic neuroprotective medicines with a complex of pleiotropic effects realized through specific orphan receptors (SUCNR1, HCA2) of glial cells, is a pressing problem of modern pharmacology and a promising possibility of pharmacotherapy of brain injury and cerebrovascular diseases. Ideally, the medicine should helps restore lost cognitive functions and physical performance after damage to the central nervous system, and its use should improve the quality of life of patients and reduce the risk of complications.Aim. To develop composition and technology of a new medicine tablets with neuroprotective effect, using fractional factorial design of experiment and the Harrington desirability function.Materials and methods. The shape and size of particles, physicochemical (solubility, melting point) and technological properties (bulk density, compressibility factor, fractional composition, hygroscopicity) of the pharmaceutical substance of DEAE derivative were studied according to the methods described in the State Pharmacopoeia of the Russian Federation (14th edition). A three-factor fractional plan based on the 4 × 4 Latin square design for selection a scientifically based composition of solid dosage form was chosen. 16 experiments to test the significance of the factors were carried out. The tablets obtained according to the planning matrix were investigated for disintegration; tablet crush resistance, friability, and hygroscopicity. To optimize the quality of the tablets, the generalized Harrington desirability function was used.Results and discussion. The study of the physicochemical and technological properties of the DEAE derivative substance showed that it is a highly hygroscopic, amorphous, white or pale yellow, odourless powder, prone to the formation of agglomerates. The powder is very easily soluble in water. Taking into account the values of the general desirability function, the best result was shown by sample № 4 consisting of mannitol, calcium stearate, and partially pregelatinized maize starch.Conclusion. The physicochemical and technological properties of the DEAE derivative were studied. The DEAE derivative is a highly hygroscopic substance. Via the method of mathematical planning of the experiment the composition of DEAE derivative tablets was selected and scientifically grounded: DEAE derivative 60 mg, mannitol, partially pregelatinized maize starch, calcium stearate. The average tablet weight is 300 mg. The parameters of pressing tablets were selected.

Cytoflavin in patients with vertigo and dizziness in a distant period of mild traumatic brain injury

To study the efficacy and safety of the complex metabolic neuroprotective medicine cytoflavin in tablet form in patients with vertigo and dizziness in a distant period of mild traumatic brain injury. Forty patients, aged 20-55 years, with a mild traumatic brain injury were studied for 3 months to 1 year. Cytoflavin was used as monotherapy in a dose of 2 tablets 2 times a day for 25 days. Otoneurological and stabilometric examinations were performed before and after treatment. The Dizziness Handicap Inventory, a visual-analogous scale and HADS were administered. Cytoflavin decreases the severity of vertigo and dizziness, improves stabilometric indicators and reduces emotional disorders in patients with vertigo in the distant period of mild traumatic brain injury. No significant adverse reactions are observed.

Normal aging hyperactivates innate immunity and reduces the medical efficacy of minocycline in brain injury

Symptoms of many neurodegenerative diseases appear later in human life. However, young animal models for penetrating traumatic brain injury (pTBI) have been used to study neurodegenerative diseases and evaluate the efficacy of neuroprotective medicines. Possibly because of this discordance, effective neuroprotective drugs have still not been developed. For patients suffering from pTBI, aging is known to be a significant prognostic factor of mortality. In this study, we aimed to establish a model of aged pTBI animals using Drosophila melanogaster. We successfully generated aged pTBI flies as a new pTBI model showing increased neurodegeneration and higher mortality. To elucidate the mechanism of increased vulnerability in aged pTBI animals, we analyzed the GenBank-deposited transcriptome data of young and aged flies, demonstrating the importance of innate immunity genes for higher mortality in aged pTBI models. We found that in the context of pTBI, normal aging strongly activated the expression of antimicrobial peptide genes and upregulated the nuclear factor-κB gene in the immune deficiency pathway, but not the Toll pathway. Moreover, we found that minocycline increased the survival of young pTBI flies, but not aged pTBI flies. These results suggested that immune system activation under neurodegenerative conditions was involved in normal aging, thereby inhibiting the medicinal efficacy of neuroprotective drugs effective for young flies in aged flies.

Pharmacoeconomic analysis of the neuroprotective medicines in the treatment of ischemic stroke

To perform a pharmacoeconomic analysis of the most frequently prescribed neuroprotective medicines for treating patients with mild ischemic stroke in the acute and early rehabilitation periods in the Russian Federation. Three medical technologies were compared: ethylmethylhydroxypyridine succinate (mexidol), inosine + nicotinamide + riboflavin + succinic acid (cytoflavin) and a deproteinized hemoderivate of the blood of calves (actovegin). Cost minimization analysis, budget impact analysis and sensitivity analysis were performed based on the indirect comparison results. Efficacy analysis shows that mentioned above medicines have the same efficacy: mean difference mexidol is 0,2 (CI min 0,25; max 0,65), cytoflavin - 0,61 (CI min 0,23; max 0,99), actovegin 0,2 (CI min 0,18; max 0,22). The cost minimization analysis for the Russian Federation shows that mexidol therapy is associated with the lowest costs, while savings are observed both in the evaluation of total costs and separate components: intravenous ampoules and tablet forms. The savings in comparison with cytoflavin and actovegin are 231 RUB and 12,872 RUB, respectively. These savings will be enough to treat five patients with ischemic stroke (IS) with mexidol. Moreover, oral mexidol therapy is cheaper than the same dosage forms of cytoflavin and actovegin by 481 RUB and 3,164 RUB, respectively. This is an advantage for the treatment of population at the outpatient stage. Budget impact analysis has shown that the budget for the medicines for treating IS at the current distribution between treatment regimens, is estimated at 1.99 BN RUB. The increase in the proportion of patients receiving mexidol by 10% reduces total costs to 1.75 BN RUB, which is 240 M RUB less than current costs. With these savings 85 thousand patients with IS could be treated. The sensitivity analysis reveals that the result of the cost minimization analysis and the budget impact analysis remain stable when both the amount of the population and the cost of 1 mg of mexidol vary from -10% to + 10%. Mexidol has the same efficacy as alternatives. However mexidol is superior to cytoflavin and actovegin in terms of cost minimization analysis. The savings from one course of alternatives will cover costs of treatment of five patients with IS using mexidol. The increase in the proportion of patients receiving mexidol is associated with savings, which allows us to consider mexidol therapy of mild IS as budget-saving in the Russian Federation.

A rodent model of anterior ischemic optic neuropathy (AION) based on laser photoactivation of verteporfin

BackgroundA rodent model of photodynamic AION resulting from intravenous verteporfin is presented. The analysis of the morphological function, the pathological changes and the potential mechanism of action were further investigated.MethodsPhotodynamic treatment was conducted on the optic nerve head (ONH) following administration of the photosensitizer. The fellow eye was considered as sham control. Fundus Fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and Flash-visual evoked potential (F-VEP) recordings were conducted at different time points. Immunohistochemistry was used to observe apoptotic cell death (TUNEL) and macrophage infiltration (ED-1/Iba-1). Retrograde labeling of retinal ganglion cells (RGCs) was used to evaluate the loss of RGCs.ResultsAfter laser treatment, SD-OCT indicated optic nerve edema, while FFA indicated late leakage of the ONH. F-VEPs were distinctly reduced compared to control eyes. The number of apoptotic RGCs peaked on day 14 (5.71 ± 0.76, p < 0.01). The infiltration of ED-1 and Iba-1 increased on the 3rd day following PDT, while it peaked on day 14 (67.5 ± 9.57 and 77.5 ± 12.58 respectively, p < 0.01). Following 3 weeks of AION, the densities of RGCs in the central retinas of the normal and AION eyes were 3075 ± 298/mm2 and 2078 ± 141/mm2 (p < 0.01), respectively.ConclusionsVerteporfin photodynamic treatment on rodents ONH can lead to functional, histological, and pathological changes. This type of animal model of AION is easy to establish and stable. It can be used for studying the mechanism and neuroprotective medicine of AION injury.

Neuro vigilance of Syzygium Cumini plant phytochemicals

According to WHO international and national status, Central Nervous System (CNS) problems (neurological disorders: Alzheimers, dementia, epilepsy, multiple sclerosis, neuroinfections, neurological disorders associated with malnutrition, pain associated with neurological disorders, Parkinson’s disease, stroke and traumatic brain injuries) are getting worse day by day because of lifestyle, environmental imbalance and genetic problems. In 2015 WHO reported that the prevalence of CNS problems is 27.8 in 1000 and 3 people in every 100 are facing any of these CNS problems. However, unfortunately, chemically synthesized drugs used to control these problems in patients poses side effects, and therefore we need natural neuroprotective agents to avoid such complications. Syzygium cumini is herbal, a medicinal plant with reported medicinal properties in various traditional and modern medicines. Plant phytochemicals from stem bark, leaves, flowers, fruits and seeds of Syzygium cumini were using to treat many diseases in modern medicine also. So far, it is used mostly to treat diabetes mellitus, pain, inflammation, ulcers, and diarrhea, and in the recent studies, it was proven that Syzygium cuminicould be used as chemopreventive, radioprotective and antineoplastic. Although the therapeutic efficacy of SZ is studied well for many systemic diseases including diabetes, much needs to be explored on its role in neurological diseases. The phytochemicals present in different parts of SZ were showing evidence that it can show neuroprotection effectively. Those phytochemicals which were already studied as neuroprotection in them, a fine number of those phytochemicals are present in Syzygium cumini. It is intimating us that Syzygium cumini can be used as an effective neuroprotective natural medicine. In this review, we elaborated there may be a possibility of potentially effective treatment with different phytochemical that has the neuroprotective effect in one plant.

Complex network analysis on dynamic change regularity of combining use of Chinese and western medicine in 27 678 cases with ischemic stroke in acute phase

The acute phase of ischemic stroke patients are often treated with both Chinese patent medicine:and western medicine therapies in clinical practice. This research included 27,678 cases of the acute phase of ischemic stroke came from 14 3A level hospitals. We collected data from patients with ischemic stroke who used both Chinese patent medicine and western medicine and were hopitalized within 14 days from hospital information system (HIS). Constructing complex network of Chinese patent medicine and western medicine were found to show scale-free network. Hierarchical structure of the core algorithm was used to analyze the characteristics of combined core Chinese patent medicine and western medicine in admission condition of "acute", "critically", and "general" of ischemic stroke acute phase patient within one day, 2-3 days, 4-7 days and 8-14 days. We found that the core Chinese patent medicine mainly used for activate blood and resolve stasis medicine, and phlegm eliminating brain refreshing medicine in all kinds of patients, but the phlegm eliminating brain refreshing medicine were used to reduce with time elapsing. The core western medicine mainly used for anti-platelet medicine, improve circulation medicine, neuroprotective medicine, anticoagulants medicine and dehydration medicine. The dehydration medicine as the core western medicine for critically patients within 14 days, but the patients for general admission as core western medicine within 3 days. The neuroprotective medicine was used to decreases after 7 days in hospital. Combination of Chinese patent medicine and western medicine were mainly for neuroprotective medicine + activate blood and resolve stasis medicine, and anti-platelet medicine + activate blood and resolve stasis medicine, and improve circulation medicine + activate blood and resolve stasis medicine. The phlegm eliminating brain refreshing medicine was mainly combined with neuroprotective medicine by urgent and general admission condition patients, and it was more combined with dehydration medicine by critically admission condition patients. This research found that the dynamic characteristics for the combination of Chinese patent medicine and western medicine of acute phase of ischemic stroke patients by big data analytics and complex networks modeling, and provide basis for acute phase of ischemic stroke patients, it provide basis for ischemic stroke treatment strategy making.

Neuroprotective effects of mercaptoethylleonurine and mercaptoethylguanidine analogs on hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells

A series of mercaptoethylleonurine and mercaptoethylguanidine derivatives were designed and synthesized. Their neuroprotective effects toward H2O2-induced apoptosis were investigated in human SH-SY5Y cells. The results from these studies identified several potent compounds, with compound 8k emerging as the most effective. Further investigation demonstrated that 8k reduced H2O2-induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of Bcl-2. Moreover, the molecular mechanism underlying the observed neuroprotective effects of 8k was exerted via the Akt and JNK pathways. Compound 8k can be a lead compound for further discovery of neuroprotective medicine.

Stabilizers of Neuronal and Mitochondrial Calcium Cycling as a Strategy for Developing a Medicine for Alzheimer's Disease

For the last two decades, most efforts on new drug development to treat Alzheimer's disease have been focused to inhibit the synthesis of amyloid beta (Aβ), to prevent Aβ deposition, or to clear up Aβ plaques from the brain of Alzheimer's disease (AD) patients. Other pathogenic mechanisms such as the hyperphosphorylation of the microtubular tau protein (that forms neurofibrillary tangles) have also been addressed as, for instance, with inhibitors of the enzyme glycogen synthase-3 kinase beta (GSK3β). However, in spite of their proven efficacy in animal models of AD, all these compounds have so far failed in clinical trials done in AD patients. It seems therefore desirable to explore new concepts and strategies in the field of drug development for AD. We analyze here our hypothesis that a trifunctional chemical entity acting on the L subtype of voltage-dependent Ca(2+) channels (VDCCs) and on the mitochondrial Na(+)/Ca(2+) exchanger (MNCX), and having additional antioxidant properties, may efficiently delay or stop the death of vulnerable neurons in the brain of AD patients. In recent years, evidence has accumulated indicating that enhanced neuronal Ca(2+) cycling (NCC) and futile mitochondrial Ca(2+) cycling (MCC) are central stage in activating calpain and calcineurin, as well as the intrinsic mitochondrial pathway for apoptosis, leading to death of vulnerable neurons. An additional contributing factor to neuronal death is the excess free radical production linked to distortion of Ca(2+) homeostasis. We propose that an hybrid compound containing a dihydropyridine moiety (to block L channels and mitigate Ca(2+) entry) and a benzothiazepine moiety (to block the MNCX and slow down the rate of Ca(2+) efflux from the mitochondrial matrix into the cytosol), as well as a polyphenol moiety (to sequester excess free radicals) could break down the pathological enhanced NCC and MCC, thus delaying the initiation of apoptosis and the death of vulnerable neurons. In so doing, such a trifunctional compound could eventually become a neuroprotective medicine capable of delaying disease progression in AD patients.