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1.
Research progress of natural products for the treatment of ischemic stroke.
Li, J, Zhao, T, Qiao, H, Li, Y, Xia, M, Wang, X, Liu, C, Zheng, T, Chen, R, Xie, Y, et al
Journal of integrative neuroscience. 2022;(1):14
Abstract
Stroke is a leading cause of death and disability world-widely. The incidence rate of stroke has been increasing due to the aging population and lifestyle changes. At present, the only drug approved by the US Food and Drug Administration (FDA) for the treatment of ischemic stroke is tissue plasminogen activator (t-PA), but its clinical application is greatly limited because of its narrow time window and bleeding risk. Natural products have a long history of being used in traditional medicine with good safety, making them an important resource for the development of new drugs. Indeed, some natural products can target a variety of pathophysiological processes related to stroke, including oxidative stress, inflammation and neuronal apoptosis. Therefore, the development of high-efficiency, low-toxicity, safe and cheap active substances from natural products is of great significance for improving the treatment alternatives of patients with stroke. This article reviews the neuroprotective effects of 33 natural compounds by searching recent related literature. Among them, puerarin, pinocembrin, quercetin, epigallocatechin-3-gallate (EGCG), and resveratrol have great potential in the clinical treatment of ischemic stroke. This review will provide a powerful reference for screening natural compounds with potential clinical application value in ischemic stroke or synthesizing new neuroprotective agents with natural compounds as lead compounds.
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2.
Flavanols from Nature: A Phytochemistry and Biological Activity Review.
Luo, Y, Jian, Y, Liu, Y, Jiang, S, Muhammad, D, Wang, W
Molecules (Basel, Switzerland). 2022;(3)
Abstract
Flavanols, a common class of secondary plant metabolites, exhibit several beneficial health properties by acting as antioxidant, anticarcinogen, cardioprotective, anti-microbial, anti-viral, and neuroprotective agents. Furthermore, some flavanols are considered functional ingredients in dairy products. Based on their structural features and health-promoting functions, flavanols have gained the attention of pharmacologists and botanists worldwide. This review collects and summarizes 121 flavanols comprising four categories: flavan-3-ols, flavan-4-ols, isoflavan-4-ols, and flavan-3,4-ols. The research of the various structural features and pharmacological activities of flavanols and their derivatives aims to lay the groundwork for subsequent research and expect to provide mentality and inspiration for the research. The current study provides a starting point for further research and development.
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3.
Inhibiting ferroptosis: A novel approach for stroke therapeutics.
Jin, Y, Zhuang, Y, Liu, M, Che, J, Dong, X
Drug discovery today. 2021;(4):916-930
Abstract
Stroke ranks as the second leading cause of death across the globe. Despite advances in stroke therapeutics, no US Food and Drug Administration (FDA)-approved drugs that can minimize neuronal injury and restore neurological function are clinically available. Ferroptosis, a regulated iron-dependent form of nonapoptotic cell death, has been shown to contribute to stroke-mediated neuronal damage. Inhibitors of ferroptosis have also been validated in several stroke models of ischemia or intracerebral hemorrhage. Herein, we review the therapeutic activity of inhibitors of ferroptosis in stroke models. We further summarize previously reported neuroprotectants that show protective effects in stroke models that have been recently validated as ferroptosis inhibitors. These findings reveal new mechanisms for neuroprotection and highlight the importance of ferroptosis during stroke processes.
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4.
Essential Oils as a Potential Neuroprotective Remedy for Age-Related Neurodegenerative Diseases: A Review.
Abd Rashed, A, Abd Rahman, AZ, Rathi, DNG
Molecules (Basel, Switzerland). 2021;(4)
Abstract
Despite the improvements in life expectancy, neurodegenerative conditions have arguably become the most dreaded maladies of older people. The neuroprotective and anti-ageing potentials of essential oils (EOs) are widely evaluated around the globe. The objective of this review is to analyse the effectiveness of EOs as neuroprotective remedies among the four common age-related neurodegenerative diseases. The literature was extracted from three databases (PubMed, Web of Science and Google Scholar) between the years of 2010 to 2020 using the medical subject heading (MeSH) terms "essential oil", crossed with "Alzheimer's disease (AD)", "Huntington's disease (HD)", "Parkinson's disease (PD)" or "amyotrophic lateral sclerosis (ALS)". Eighty three percent (83%) of the studies were focused on AD, while another 12% focused on PD. No classifiable study was recorded on HD or ALS. EO from Salvia officinalis has been recorded as one of the most effective acetylcholinesterase and butyrylcholinesterase inhibitors. However, only Cinnamomum sp. has been assessed for its effectiveness in both AD and PD. Our review provided useful evidence on EOs as potential neuroprotective remedies for age-related neurodegenerative diseases.
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5.
Blood-brain barrier dysfunction in hemorrhagic transformation: a therapeutic opportunity for nanoparticles and melatonin.
Figueroa, EG, González-Candia, A, Caballero-Román, A, Fornaguera, C, Escribano-Ferrer, E, García-Celma, MJ, Herrera, EA
Journal of neurophysiology. 2021;(6):2025-2033
Abstract
Stroke is the second leading cause of death worldwide, estimated that one-sixth of the world population will suffer it once in their life. The most common type of this medical condition is the ischemic stroke (IS), produced by a thrombotic or embolic occlusion of a major cerebral artery or its branches, leading to the formation of a complex infarct region caused by oxidative stress, excitotoxicity, and endothelial dysfunction. Nowadays, the immediate treatment for IS involves thrombolytic agents or mechanical thrombectomy, depending on the integrity of the blood-brain barrier (BBB). A common stroke complication is the hemorrhagic transformation (HT), which consists of bleeding into the ischemic brain area. Currently, better treatments for IS are urgently needed. As such, the neurohormone melatonin has been proposed as a good candidate due to its antioxidant, anti-inflammatory, and neuroprotective effects, particularly against lipid peroxidation and oxidative stress during brain ischemia. Here, we proposed to develop intravenous or intranasal melatonin nanoformulation to specifically target the brain in patients with stroke. Nowadays, the challenge is to find a formulation able to cross the barriers and reach the target organ in an effective dose to generate the pharmacological effect. In this review, we discuss the current literature about stroke pathophysiology, melatonin properties, and its potential use in nanoformulations as a novel therapeutic approach for ischemic stroke.
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6.
Role of luteolin in overcoming Parkinson's disease.
Siddique, YH
BioFactors (Oxford, England). 2021;(2):198-206
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting elderly people (>60 years old) worldwide. There is no permanent cure for the disease but the symptomatic relief can be obtained by using dopamine agonists besides L-dopa therapy. The longer use of the drugs is associated with several side effects. Hence, the researchers have made a considerable attention toward the development of neuroprotective agents from plants. A number of phytochemicals have been demonstrated for their protective effects in various in vitro, in vivo, and clinical studies. In this context, luteolin, a flavone which is present in fruits and vegetables has been attributed to a number of pharmacological properties including neuroprotective. The present review demonstrates the bioavailability, oral absorption, and mechanism of action against PD.
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7.
[Effects of the use of 17 β-estradiol and genistein in Alzheimer's disease in women with menopause].
Chávez-Pérez, C, Ceballos-Ramírez, A, Suárez-Castro, A
Revista espanola de geriatria y gerontologia. 2021;(4):236-240
Abstract
The use of 17 β-estradiol and genistein in women with menopause helps in the reduction of vasomotor symptoms and cognitive improvement. There is evidence on the use of certain flavonoids such as genistein, which has a potentially neuroprotective role in neurodegenerative diseases such as Alzheimer's. Scientific evidence on the effects of phytoestrogens and genistein during menopause and their effect on cognition are scarce, however, in the present review it was found that the intervention with 17 β-estradiol has positive effects on cognition in women with Alzheimer's disease. In addition, the use of genistein, daidzein or any supplement based on isoflavones may influence vasomotor symptoms. 17 β-estradiol supplements in women in early menopause and with some degree of cognitive impairment may have beneficial effects.
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8.
Improvement of a Novel Proposal for Antioxidant Treatment Against Brain Damage Occurring in Ischemic Stroke Patients.
Orellana-Urzúa, S, Claps, G, Rodrigo, R
CNS & neurological disorders drug targets. 2021;(1):3-21
Abstract
The underlying mechanism of cerebral injury occurring in patients with acute ischemic stroke involves a key pathophysiological role of oxidative stress. Thus, reactive oxygen species are related to the development of brain edema, calcium overload, mitochondrial dysfunction, excitotoxicity, iron release and inflammation. Nevertheless, although experimental studies have tested the use of antioxidants as an adjuvant therapy in this setting, clinical data and randomized trials are still lacking. Current approved pharmacological therapy is aimed at reperfusion strategies; however, the therapeutic window is limited and also challenged by the injury known to result from the reperfusion. We have recently defined a time-course occurrence of pathological events triggered by reperfusion-dependent increased reactive oxygen species, thus suggesting the beneficial role of the pertinent use of antioxidants. The present study was aimed to support the hypothesis that an enhanced antioxidant neuroprotection could be achieved by the use of two or more antioxidants opportunely provided to ischemic stroke patients focused against the specific mechanism occurring throughout the pathophysiological process. From this paradigm, using an underexplored therapeutic principle, it could be suggested that antioxidant-based therapy is a novel, promising, safe, available and cost-effective strategy against the deleterious effects of ischemic stroke that needs to be further studied in clinical protocols.
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9.
Emerging agents for the treatment and prevention of stroke: progress in clinical trials.
Safouris, A, Magoufis, G, Tsivgoulis, G
Expert opinion on investigational drugs. 2021;(10):1025-1035
Abstract
INTRODUCTION Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients. AREAS COVERED The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an alternative thrombolytic drug to alteplase, nerinetide as a promising neuroprotective agent, and glibenclamide for reducing edema in malignant hemispheric infarction. We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, as well as novel antidiabetic agents that have been shown to reduce cardiovascular events in the long-term. EXPERT OPINION Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical agents. This tendency enriches the therapeutic armamentarium with novel agents developed for specific stroke subgroups. ABBREVIATIONS IVT: intravenous thrombolysis; RCTs: randomized-controlled clinical trials; TNK: Tenecteplase; COVID-19: Coronavirus 2019 Disease; EXTEND-IA TNK The Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke trial; AIS: acute ischemic stroke; NNT: number needed to treat; MT: mechanical thrombectomy; sICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; AHA/ASA: American Heart Association/American Stroke Association; ESO: European Stroke Organization; NA-1: Nerinetide; ENACT Evaluating Neuroprotection in Aneurysm Coiling Therapy; CTA: CT angiography; TIA: transient ischemic attack; CHANCE Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; LOF: loss-of-function; PRINCE Platelet Reactivity in Acute Nondisabling Cerebrovascular Events; THALES Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death; CHANCE-2: Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II; FXI: Factor XI; PACIFIC-STROKE Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-NonCardioembolic Stroke study; COMPASS Cardiovascular Outcomes for People Using Anticoagulation Strategies; CANTOS-ICAD: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease; SAMMPRIS Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis; WASID Warfarin-Aspirin Symptomatic Intracranial Disease; SPARCL Stroke Prevention by Aggressive Reduction in Cholesterol Levels; LDL-C: low-density lipoprotein cholesterol; TST: Treat Stroke to Target; IMPROVE-IT: Improved Reduction of Outcomes: Vytorin Efficacy International Trial; PCSK9: proprotein convertase subtilisin-kexin type 9; FOURIER Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; CLEAR Cholesterol Lowering via Bempedoic acid, an ACL-inhibiting Regimen; REDUCE-IT: Reduction of Cardiovascular Events With EPA Intervention Trial; STRENGTH Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia; ACCORD Action to Control Cardiovascular Risk in Diabetes; ADVANCE Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; VADT Veterans Affairs Diabetes Trial; GLP-1R: Glucagon-like peptide-1 receptor; SGLT2: sodium-glucose cotransporter 2; CONVINCE COlchicine for preventioN of Vascular Inflammation in Non-CardioEmbolic stroke; PROBE Prospective Randomized Open-label Blinded Endpoint assessment.
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10.
Targeted pharmacotherapy against neurodegeneration and neuroinflammation in early diabetic retinopathy.
Rolev, KD, Shu, XS, Ying, Y
Neuropharmacology. 2021;:108498
Abstract
Diabetic retinopathy (DR), the most frequent complication of diabetes, is one of the leading causes of irreversible blindness in working-age adults and has traditionally been regarded as a microvascular disease. However, increasing evidence has revealed that synaptic neurodegeneration of retinal ganglion cells (RGCs) and activation of glial cells may represent some of the earliest events in the pathogenesis of DR. Upon diabetes-induced metabolic stress, abnormal glycogen synthase kinase-3β (GSK-3β) activation drives tau hyperphosphorylation and β-catenin downregulation, leading to mitochondrial impairment and synaptic neurodegeneration prior to RGC apoptosis. Moreover, glial cell activation triggers enhanced inflammation and oxidative stress, which may accelerate the deterioration of diabetic RGCs neurodegeneration. These findings have opened up opportunities for therapies, such as inhibition of GSK-3β, glial cell activation, glutamate excitotoxicity and the use of neuroprotective drugs targeting early neurodegenerative processes in the retina and halting the progression of DR before the manifestation of microvascular abnormalities. Such interventions could potentially remedy early neurodegeneration and help prevent vision loss in people suffering from DR.