The neuroprotective effects of astaxanthin: therapeutic targets and clinical perspective

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also consideredS

Prediction of Neurological Enzyme Targets for Known and New Compounds with a Model using Galvez's Topological Indices

The 18th International Electronic Conference on Synthetic Organic Chemistry session Computational ChemistryAlzheimer's Disease (AD), Parkinson, and other neurodegenerative diseases are a major health problem nowadays. In this sense, the discovery of new drugs for neurodiseases treatment is a goal of the major importance. Public databases, like ChEMBL, contain a large amount of data about multiplexing assays of inhibitors of a group of enzymes with special relevance in central nervous system. Mono Amino Oxidases (MAOs), Acetyl Cholinesterase (AChE), Glycogen Synthase Kinase-3 (GSK-3), AChE (AChE), and 5α-reductases (5αRs). This data conform an important information source for the application of multi-target computational models. However, almost all the computational models known focus in only one target. In this work, we developed mt-QSAR for inhibitors of 8 different enzymes promising in the treatment of different neurodiseases. In so doing, we combined by the first time the software DRAGON with Moving Average parameters with this objective. The best DRAGON model found predict with very high accuracy, specificity, and sensitivity >90% a very large data set >10000 cases in training and validation series. We also report experimental results about the assay of several 7

El saber pedagógico y epistémico en educación especial y su reto migratorio hacia la educación inclusiva

The purpose of this article of reflection is to share ideas of the comprehensive framework in the pedagogical and epistemic knowledge of Special Education. What it allows, to address the constructions facing the paradigmatic shift of migration towards an Inclusive Education that from the XX century takes a leading character in the pedagogical knowledge of Latin American education. Among the discourses that Inclusive Education involves, there is equality of opportunities, with evident epistemological gaps within pedagogical knowledge, generating hybrid and incoherent subtleties referring to the challenges and dilemmas that the inclusion of students in traditional educational systems tends to. These paradigmatic and epistemological dilemmas that surround this migration of a traditional knowledge in Special Education, is the reason for critical analysis, which is bearable to problematize the inconsistencies that are being generated as a result of the re-signification of a pedagogy, that from its Early considered an education under normalization processes, with exclusionary and even tendencies and that currently presents transforming ideas, on an approach in evolution that seeks an episteme based on Inclusive Education.El propósito del presente artículo de reflexión es compartir ideas del marco comprensivo en el saber pedagógico y epistémico de la Educación Especial. Lo que permite, abordar las construcciones que enfrenta el cambio paradigmático de migración hacia una Educación Inclusiva, que a partir del siglo XX toma un carácter protagónico en los saberes pedagógicos de la educación latinoamericana. Entre los discursos que involucra la Educación Inclusiva, se encuentra la igualdad de oportunidades, con evidentes vacíos epistemológicos al interior del saber pedagógico, generando sutilezas híbridas e incoherentes referente a los desafíos y dilemas que propende la inclusión de estudiantes en los sistemas educativos tradicionales. Estos dilemas paradigmáticos y epistemológicos que ronda esta migración de una tradicionalidad de saberes en la Educación Especial, es el motivo de análisis crítico, que es llevadero para problematizar las inconsistencias que se están generando producto de la re-significación de una pedagogía, que desde sus inicios consideró una educación bajo procesos de normalización, con tendencias exclusoras e inclusoras y que actualmente presenta ideas transformista, sobre un enfoque en evolución que busca una episteme fundada en la Educación Inclusiva

Hesperidin as a neuroprotective agent: a review of animal and clinical evidence

Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical studies on the role of hesperidin in the neurodegenerative diseases, less is known about its definite effect on humans. A limited number of clinical trials showed that hesperidin-enriched dietary supplements can significantly improve cerebral blood flow, cognition, and memory performance. Further clinical trials are also required for confirming neuroprotective efficacy of this natural flavonoid and evaluating its safety profileS

El saber pedagógico y epistémico en educación especial y su reto migratorio hacia la educación inclusiva

The purpose of this article of reflection is to share ideas of the comprehensive framework in the pedagogical and epistemic knowledge of Special Education. What it allows, to address the constructions facing the paradigmatic shift of migration towards an Inclusive Education that from the XX century takes a leading character in the pedagogical knowledge of Latin American education. Among the discourses that Inclusive Education involves, there is equality of opportunities, with evident epistemological gaps within pedagogical knowledge, generating hybrid and incoherent subtleties referring to the challenges and dilemmas that the inclusion of students in traditional educational systems tends to. These paradigmatic and epistemological dilemmas that surround this migration of a traditional knowledge in Special Education, is the reason for critical analysis, which is bearable to problematize the inconsistencies that are being generated as a result of the re-signification of a pedagogy, that from its Early considered an education under normalization processes, with exclusionary and even tendencies and that currently presents transforming ideas, on an approach in evolution that seeks an episteme based on Inclusive Education.El propósito del presente artículo de reflexión es compartir ideas del marco comprensivo en el saber pedagógico y epistémico de la Educación Especial. Lo que permite, abordar las construcciones que enfrenta el cambio paradigmático de migración hacia una Educación Inclusiva, que a partir del siglo XX toma un carácter protagónico en los saberes pedagógicos de la educación latinoamericana. Entre los discursos que involucra la Educación Inclusiva, se encuentra la igualdad de oportunidades, con evidentes vacíos epistemológicos al interior del saber pedagógico, generando sutilezas híbridas e incoherentes referente a los desafíos y dilemas que propende la inclusión de estudiantes en los sistemas educativos tradicionales. Estos dilemas paradigmáticos y epistemológicos que ronda esta migración de una tradicionalidad de saberes en la Educación Especial, es el motivo de análisis crítico, que es llevadero para problematizar las inconsistencias que se están generando producto de la re-significación de una pedagogía, que desde sus inicios consideró una educación bajo procesos de normalización, con tendencias exclusoras e inclusoras y que actualmente presenta ideas transformista, sobre un enfoque en evolución que busca una episteme fundada en la Educación Inclusiva

Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host–pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidatesJ.E. gratefully acknowledges funding from CONICYT (PAI/ACADEMIA N°79160109)S

Antiangiogenic effects of coumarins against cancer: from chemistry to medicine

Angiogenesis, the process of formation and recruitment of new blood vessels from pre-existing vessels, plays an important role in the development of cancer. Therefore, the use of antiangiogenic agents is one of the most critical strategies for the treatment of cancer. In addition, the complexity of cancer pathogenicity raises the need for multi-targeting agents. Coumarins are multi-targeting natural agents belonging to the class of benzopyrones. Coumarins have several biological and pharmacological effects, including antimicrobial, antioxidant, anti-inflammation, anticoagulant, anxiolytic, analgesic, and anticancer properties. Several reports have shown that the anticancer effect of coumarins and their derivatives are mediated through targeting angiogenesis by modulating the functions of vascular endothelial growth factor as well as vascular endothelial growth factor receptor 2, which are involved in cancer pathogenesis. In the present review, we focus on the antiangiogenic effects of coumarins and related structure-activity relationships with particular emphasis on cancerS

Ageratum conyzoides L. and Its Secondary Metabolites in the Management of Different Fungal Pathogens

Ageratum conyzoides L. (Family—Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant’s dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discoveryS

Natural Products for Neurodegeneration: Regulating Neurotrophic Signals

Neurodegenerative disorders (NDs) are heterogeneous groups of ailments typically characterized by progressive damage of the nervous system. Several drugs are used to treat NDs but they have only symptomatic benefits with various side effects. Numerous researches have been performed to prove the advantages of phytochemicals for the treatment of NDs. Furthermore, phytochemicals such as polyphenols might play a pivotal role in rescue from neurodegeneration due to their various effects as anti-inflammatory, antioxidative, and antiamyloidogenic agents by controlling apoptotic factors, neurotrophic factors (NTFs), free radical scavenging system, and mitochondrial stress. On the other hand, neurotrophins (NTs) including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT4/5, and NT3 might have a crucial neuroprotective role, and their diminution triggers the development of the NDs. Polyphenols can interfere directly with intracellular signaling molecules to alter brain activity. Several natural products also improve the biosynthesis of endogenous genes encoding antiapoptotic Bcl-2 as well as NTFs such as glial cell and brain-derived NTFs. Various epidemiological studies have demonstrated that the initiation of these genes could play an essential role in the neuroprotective function of dietary compounds. Hence, targeting NTs might represent a promising approach for the management of NDs. In this review, we focus on the natural product-mediated neurotrophic signal-modulating cascades, which are involved in the neuroprotective effectsThis work was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding ProgramS