RESUMEN
Neuronal survival and axonal renewal following central nervous system damage and in neurodegenerative illnesses, such as Alzheimer's disease (AD), can be enhanced by fast clearance of neuronal apoptotic debris, as well as the removal of amyloid beta (Aß) by phagocytic cells through the process of efferocytosis. This process quickly inhibits the release of proinflammatory and antigenic autoimmune constituents, enhancing the formation of a microenvironment vital for neuronal survival and axonal regeneration. Therefore, the detrimental features associated with microglial phagocytosis uncoupling, such as the accumulation of apoptotic cells, inflammation and phagoptosis, could exacerbate the pathology in brain disease. Some mechanisms of efferocytosis could be targeted by several promising agents, such as curcumin, URMC-099 and Y-P30, which have emerged as potential treatments for AD. This review aims to investigate and update the current research regarding the signaling molecules and pathways involved in efferocytosis and how these could be targeted as a potential therapy in AD.
Asunto(s)
Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Apoptosis , Encéfalo/patología , Microglía/patología , Neuronas/patología , Fagocitosis , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Humanos , Microglía/efectos de los fármacos , Microglía/metabolismo , Terapia Molecular Dirigida , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Fagocitosis/efectos de los fármacosRESUMEN
BACKGROUND: The conjugates of the sesquiterpene lactone of the eremophilane series of 6- hydroxyxanthanodiene with hydrogenated azines (piperidines and piperazines) have been synthesized and identified by NMR spectrometer. OBJECTIVE: A lactone with an unusual skeleton "6-hydroxyxanthanodiene" was extracted from the plant Elecampane (Inula helenium L) and identified various species with NMR spectrometer. METHODS: The cytotoxic, mitochondrial, and antioxidant activities on different tumor lines such as A549, HCT116, RD and Jurkat were investigated and determined possible mechanisms. RESULTS: The results showed that the most potent compound was IIIi exhibiting highest cytotoxicity against RD cells (IC50 25.23 ± 0.04 µM), depolarized the mitochondrial membrane and was an effective antioxidant (IC50 inhibition of LP 10.68 ± 3.21 µM) without any toxic side effect on healthy cells. CONCLUSION: The conjugates of sesquiterpene lactone 6-hydroxyxanthanodiene III and hydrogenated azines may help to design potential promising anticancer drugs.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Inula/química , Lactonas/farmacología , Extractos Vegetales/farmacología , Sesquiterpenos/farmacología , Células A549 , Animales , Antineoplásicos Fitogénicos/química , Antioxidantes/química , Supervivencia Celular/efectos de los fármacos , Células HCT116 , Humanos , Concentración 50 Inhibidora , Células Jurkat , Lactonas/química , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Extractos Vegetales/química , Ratas , Sesquiterpenos/químicaRESUMEN
Curcumin (Cur) is an active derivative extracted from turmeric which exerts a wide range of interactions with biomolecules through complex signaling pathways. Cur has been extensively shown to possess potential antitumor properties. In addition, there is growing body of evidence suggesting that Cur may exert potential anti-estrogen and anti-androgen activity. In vitro and in vivo studies suggest that anticancer properties of Cur against tumors affecting the reproductive system in females and males may be underlied by the Cur-mediated inhibition of androgen and estrogen signaling pathways. In this review we examine various studies assessing the crosstalk between Cur and both androgen and estrogen hormonal activity. Also, we discuss the potential chemopreventive and antitumor role of Cur in the most prevalent cancers affecting the reproductive system in females and males.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Curcumina/uso terapéutico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Masculinos/tratamiento farmacológico , Hormonas Esteroides Gonadales/antagonistas & inhibidores , Antagonistas de Andrógenos/efectos adversos , Animales , Antineoplásicos Fitogénicos/efectos adversos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Curcumina/efectos adversos , Moduladores de los Receptores de Estrógeno/efectos adversos , Femenino , Neoplasias de los Genitales Femeninos/metabolismo , Neoplasias de los Genitales Femeninos/patología , Neoplasias de los Genitales Masculinos/metabolismo , Neoplasias de los Genitales Masculinos/patología , Hormonas Esteroides Gonadales/metabolismo , Humanos , Masculino , Transducción de Señal , Resultado del TratamientoRESUMEN
Free radicals (FR) act on living organisms and present unpaired electrons in the molecular orbitals of oxygen or nitrogen species. They are classified as redox reactions and account for a wide range of processes in biological systems. Genetic and environmental factors may alter the levels of FR in the cell, leading to deleterious consequences such as membrane lipid peroxidation, protein nitration, enzyme, carbohydrate and DNA damage, ultimately resulting in premature aging and a pro-inflammatory microenvironment as observed in Alzheimer's disease (AD) and autism spectrum disorder (ASD). O2 radical ability to act as a Lewis base and to form a complex with metal transition such as iron and copper (Lewis acids) leads to biomolecules oxidation at physiological pH, thus increasing the possibility of injury and oxidative damage in biological tissues. In this review, we discuss the role of metals, like copper, and the amyloid precursor protein (APP) derivative (s-APP-alpha) as an antioxidant and a possible adjuvant in the treatment of some autistic spectrum disorder symptoms (ASD).
Asunto(s)
Precursor de Proteína beta-Amiloide , Trastorno del Espectro Autista , Cobre/toxicidad , Radicales Libres , Antioxidantes , Humanos , Estrés OxidativoRESUMEN
Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.
Asunto(s)
Trastornos Nutricionales/tratamiento farmacológico , Trastornos Nutricionales/etiología , Oligoelementos/deficiencia , Acetato de Zinc/uso terapéutico , Zinc/deficiencia , Animales , Estudios Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Humanos , Imidazoles/química , Ratones , Trastornos Nutricionales/diagnóstico , Trastornos Nutricionales/prevención & control , Resultado del Tratamiento , Acetato de Zinc/química , Acetato de Zinc/farmacologíaRESUMEN
Parkinson's disease is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra pars compacta region. An important mechanism contributing to its development is oxidative stress, induced by the imbalance between the endogenous antioxidant defenses and free radicals production. Naturally occurring bioactive compounds exhibit high antioxidant capacity that may help reducing oxidative stress and even reverse the damage induced by ROS. Fruits are particularly rich in phytochemicals with antioxidant effect, and their properties against the development of neurodegenerative diseases are of great interest. This review discusses how the fruits bioactive compounds and synthetic analogs have been assessed for their ability to regulate molecular pathways involved in neuronal survival such as MAPK, Nrf2, and NF-κB, thus elucidating the possible therapeutic and neuroprotective actions of these compounds.
Asunto(s)
Enfermedad de Parkinson/prevención & control , Preparaciones de Plantas/farmacología , Plantas Medicinales/química , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antiparkinsonianos/aislamiento & purificación , Antiparkinsonianos/farmacología , Neuronas Dopaminérgicas/metabolismo , Radicales Libres/metabolismo , Humanos , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/fisiopatología , Preparaciones de Plantas/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Many mental health conditions including psychiatric disorders and neurodegenerative conditions are poorly responsive for actual medications or have low patient adherence to treatment due to the side effects or costs associated with these treatments. OBJECTIVE: The main goal of this review is to provide clinical providers and patients with actualized information about the efficacy of selected herbal medicines for anxiety disorders derived from mental and/or health conditions, and their associated side effects. METHODS: In this review, actual scientific advances about the use of medicinal plants for anxiety disorders are presented. RESULTS: In recent years, the herbal therapies have reemerged as a source of efficacious natural treatments, at a lower cost and most of the time reduced side effects than currently prescribed pharmaceutical drugs. The herbs described mainly correspond to plants of traditional medicine from the American continent and near islands and Asia. CONCLUSION: Current evidence confirms the therapeutic effects of traditional medicine. Further clinical investigation is required to confirm these findings. The current understanding of the molecular mechanisms involved in psychiatric disorders, as well as the new advances in brain imaging permit a rapid and serious evaluation of anxiolytic compounds.
Asunto(s)
Ansiedad/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , Fitoterapia/métodos , Plantas Medicinales , Animales , Interacciones de Hierba-Droga , Humanos , Fitoterapia/efectos adversosRESUMEN
Green tea is a beverage consumed around the world that is believed to have substantial health benefits such as reducing the risk of cancer, cardiovascular diseases, diabetes and neurodegeneration. This beverage is prepared from the leaves (steamed and dried) of the Camellia sinesis plant and contains strong antioxidant and neuroprotective phenolic compounds from which the most important is (-)-Epigallocatechin-3-gallate. Parkinson's disease (PD) is the second more common neurodegenerative disorders, after Alzheimer's disease and is characterized by degeneration of dopaminergic neurons in the pars compact of the substantia nigra of the basal ganglia. It has been shown in pre-clinical and clinical studies that green tea may be able to prevent PD, but its optimal dose or a possible mechanism explaining its health benefit in PD has not been properly established. In this review, we discuss the potential role of green tea's phenolic compounds and their therapeutic effectin modulating key signaling pathways in the PD brain.
Asunto(s)
Catequina/análogos & derivados , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Té/química , Animales , Catequina/uso terapéutico , Humanos , Té/metabolismoRESUMEN
Retinal adhesion mechanisms in mammals are quite complex and multifactorial in nature. To date, these mechanisms are incompletely understood due to a variety of chemical, physical, and physiological forces impinging upon retinal tissue: retinal pigment epithelium, nearby tissues as sclera and vitreous, the subretinal space, and the highly complex interphotoreceptor matrix that fills subretinal space. The adhesion of the retina to the choroid, rather than anatomical, is a dynamic process, as the retina detaches a few minutes after life ceases. The adhesion mechanisms described in the literature, such as intraocular pressure and the oncotic pressure of the choroid that seems to push the retina towards the choroid, the delicate anatomical relationships between the rod and cone photoreceptors, the retinal pigment epithelium, the existence of a complex material called interphotoreceptor matrix, as well as other metabolic and structural factors, still cannot explain the remarkable features observed in the adhesion mechanisms between the photoreceptor layer and retinal pigment epithelium cells. The unexpected intrinsic property of melanin to absorb light energy and transform it into chemically based free energy can explain normal adhesion of the sensory retina to the pigment epithelium. In this article, we explore and highlight this explanation, which states that it is definitely able to provide a new treatment avenue against devastating neurodegenerative properties.