A review study on medicinal plants affecting amnesia through cholinergic system

Neurotransmitter modification is an important method for the treatment of memory loss or amnesia. Cholinomimetic drugs, particularly, acetylcholine esterase inhibitors are the mainstream in pharmacotherapy of amnesia. Donepezil, tacrine, galantamine, and rivastigmine are cholinesterase inhibitors which are widely used in the treatment of amnesia, however, their therapeutic effects are not significant. Therefore, other possibilities including herbal medicine sources have been considered for memory loss therapy. There are some Medicinal plants with cholinomimetic property which mostly possess antioxidant activity, too. These plants may not only ameliorate amnesia but also can be a good source for drug discovery. In this paper other than introducing the medicinal plants and their components affective on cholinergic system and effective on memory loss, their probable advantages over synthetic drugs are discussed

Using animal models to determine the significance of complement activation in Alzheimer's disease

Complement inflammation is a major inflammatory mechanism whose function is to promote the removal of microorganisms and the processing of immune complexes. Numerous studies have provided evidence for an increase in this process in areas of pathology in the Alzheimer's disease (AD) brain. Because complement activation proteins have been demonstrated in vitro to exert both neuroprotective and neurotoxic effects, the significance of this process in the development and progression of AD is unclear. Studies in animal models of AD, in which brain complement activation can be experimentally altered, should be of value for clarifying this issue. However, surprisingly little is known about complement activation in the transgenic animal models that are popular for studying this disorder. An optimal animal model for studying the significance of complement activation on Alzheimer's – related neuropathology should have complete complement activation associated with senile plaques, neurofibrillary tangles (if present), and dystrophic neurites. Other desirable features include both classical and alternative pathway activation, increased neuronal synthesis of native complement proteins, and evidence for an increase in complement activation prior to the development of extensive pathology. In order to determine the suitability of different animal models for studying the role of complement activation in AD, the extent of complement activation and its association with neuropathology in these models must be understood

Efecto de Ocimum basilicum y Ocimum selloi sobre el daño vascular cerebral en un modelo de hipertensión arterial crónica

Introduction: There are studies that show that endothelial dysfunction (ED) is a possible mechanism that produces high blood pressure, while others have shown that HBP generates endothelial damage. Given the existence of several clinical conditions associated with ED, the protection of the endothelium has gained great interest in the development of antihypertensive drugs that improve endothelial function beyond the reduction of blood pressure (BP). Circulating microparticle levels rise in various cardiovascular diseases. Its highest level in plasma is considered a biomarker of alteration in vascular function. The endothelial microparticles (EMP) described as vesicles (0.1 to 1.0 μm), are released in response to the activation or apoptosis of the endothelial cells. EMPs have physiological and pathological effects and can promote oxidative stress and vascular inflammation. The release of EMP is triggered by inducers such as angiotensin II (angII), lipopolysaccharide or hydrogen peroxide. In animal models of hypertension, it has been found that endothelium-dependent relaxation is reduced, possibly due to defects in the synthesis, release, inactivation of nitric oxide (NO), or by alterations in the production or expression of constrictor factors of endothelial origin. The long-term control of BP is closely related to homeostasis of the volume of fluid in the body, which is determined by the balance between ingestion and elimination of fluids, a function that is performed by various control mechanisms such as nervous , hormonal and by the local systems in the kidneys, which regulate the excretion of salt and water. The dominant characteristics of hypertension in Mexico usually require the application of two or more medications and the indication of changes in lifestyle. In the general population if the goal is not reached within a month of treatment, the dose should be increased, or a second drug added. Although they help control the symptoms related to the disease, they also generate adverse effects, since when they reach the bloodstream, they act in more than one place in the body; as a consequence, patients choose to abandon treatment, which leads to resistant or uncontrolled hypertension. Alternatives have been sought in different areas of research, whose purpose is to achieve the generation of drugs capable of acting in the prevention, regression and remediation of these conditions. Among the different complementary practices used and disseminated through popular culture, medicinal plants always occupy a prominent place and for a long time it was the main therapeutic resource used to treat the health of people. Such is the case of the species contained in the Ocimum genus, which have been used for both culinary and curative purposes. In addition, pharmacological reports indicate that they influence the cardiovascular system, are a source of antioxidant agents and have even been shown to inhibit hypertensionrelated enzymes (ACE; angII converting enzyme). Main objective: Demonstrate the antihypertensive effect of Ocimum basilicum, Ocimum Selloi and rosmarinic acid, as well as its effect on the associated comorbidities; damage to target organ, inflammation, cognitive deficit and behavioral stress. Materials and methods: With dry leaves of O. basilicum and O. selloi, two ethanolic extracts (60%) were obtained which were separated with ethyl acetate (fractions of O. basilicum: ObAEt, and O. selloi: Os-AEt), both containing rosmarinic acid (RA), so it was used as a reference. ICR mice (n = 12; 35 g. NOM-062-ZOO-1999) were used. The hypertension model consisted in the administration of angII (0.2 μg/kg ip n = 12 per group) for 12 weeks, in the 6th week of the administration all of the treatments began; vehicle (tween20 1%), telmisartan (10 mg/kg), diazepam (0.25 mg/kg), galantamine (0.2 mg/kg), Ob-AEt (25 mg/kg), Os-AEt (25 mg/kg), RA (0.39, 0.78, 1.56, 3.12 and 6.24 mg/Kg). The BP was monitored at 0, 6 and 12 weeks of the model. Subsequently, the animals underwent behavioral tests: water Morris maze (WMM; memory), elevated plus maze (EPM; anxiety), and open field (OF; motor coordination). At the end of the behavioral tests, they were sacrificed by cervical dislocation to obtain brain and kidneys for cytokine quantification, blood samples for corticosterone quantification (ELISA, and EMP (flow cytometry). Results: In the present work, the administration of angII at 0.2 μg/kg ip for 12 weeks, activated the inflammatory response mediated by cytokines, mainly by IL1β, IL6, TNFα and chemokine MCP1, in turn decreased the activity of anti-inflammatory cytokines like IL4, IL10 and TGFβ. The angII caused hypertension and anxiety, acting on AT1 receptors distributed along the hypothalamic-pituitary-adrenal (HPA) axis, generating increased corticosterone. In the different behavioral models, an anxiogenic effect was observed in the vehicle group, there was a decrease in the number of entries and time in open arms (EOA and TOA) in EPM. This effect was counteracted in a dose-dependent manner with RA: Emax = 63.69%, ED50 = 0.23 mg/Kg, for EOA; Emax = 59.17%, ED50 = 0.15 mg/Kg for TOA. When administering Oba-AEt and Os-AEt, and some doses of RA, the damage caused by angII was stopped by restoring serum corticosterone levels and decreasing proinflammatory cytokines and MCP-1. Ob-AEt, Os-AEt and AR, protected against the increase in vascular tangential stress (shear stress) generated by angII, since a significant decrease was observed in the populations of MPE AnnexinV+ /CD105+ /CD31 + and AnnexinV+ /CD105+ /CD1046+ . Conclusion: In the present work we find that the extracts obtained from O. basilicum and O. selloi have anti-inflammatory (cerebral and renal), antihypertensive, anxiolytic, nootropic effect, and do not modify the motor behavior, in addition, they prevent the endothelial dysfunction generated by the chronic administration of angII. The approach of hypertension is and will always be multidisciplinary. The need to control BP, as well as the inhibition of angII action, continue to being of the primary objectives in cardiovascular therapy, which attempts to control the long-term consequences of high blood pressure, which has raised an interesting evolution towards prevention in these high-risk patients, through the development of new medications, devices and procedures that are designed to treat hypertension and its comorbidities.Introducción: Existen estudios que demuestran que la disfunción endotelial (DE) es un posible mecanismo que produce hipertensión arterial (HTA), mientras que otros han demostrado que la HTA per se produce daño endotelial. Ante la existencia de varias condiciones clínicas asociadas a DE, la protección del endotelio ha cobrado gran interés para el desarrollo de fármacos antihipertensivos que mejoren la función endotelial, más allá de la reducción de la presión arterial (PA). Los niveles de micropartículas circulantes se elevan en diversas enfermedades cardiovasculares. Su mayor nivel en plasma se considera un biomarcador de alteración en la función vascular. Las micropartículas endoteliales (MPE), descritas como vesículas (0.1 a 1.0 μm), se liberan en respuesta a la activación o apoptosis de las células endoteliales. Las MPE poseen efectos fisiológicos y patológicos y pueden promover estrés oxidante e inflamación vascular. La liberación de MPE se desencadena por algún inductor, como la angiotensina II (angII), el lipopolisacárido o el peróxido de hidrógeno. En los modelos animales de HTA se ha encontrado que la relajación dependiente del endotelio está reducida, posiblemente por defectos en la síntesis, liberación, inactivación del óxido nítrico (NO), o por alteraciones de producción o expresión de factores constrictores de origen endotelial. El control a largo plazo de la PA está íntimamente relacionado con la homeostasis del volumen de líquido en el organismo, que está determinada por el balance entre la ingestión y la eliminación de líquidos, una función que es realizada por varios mecanismos de control como los nerviosos, hormonales y renales, que regulan la excreción de sal y agua. Las características dominantes de la HTA en México requieren usualmente la aplicación de dos o más medicamentos y obligadamente la indicación de cambios en el estilo de vida. En la población general si la meta no se alcanza en un mes de tratamiento, se debe aumentar la dosis, o bien agregar un segundo fármaco. Si bien ayudan a controlar los síntomas relacionados con la enfermedad, también les generan efectos adversos, ya que al llegar al torrente sanguíneo éstos actúan en más de un sitio en el organismo; cómo consecuencia, los pacientes optan por abandonar el tratamiento, lo que deriva a una HTA resistente o incontrolada. Se han buscado alternativas en diferentes áreas de investigación, cuyo fin es lograr la generación de fármacos capaces de actuar en la prevención, regresión y remediación de estas afecciones. Entre las distintas prácticas complementarias utilizadas y difundidas a través de la cultura popular, las plantas medicinales siempre ocupan lugar destacado y durante mucho tiempo fue el principal recurso terapéutico utilizado para tratar la salud de las personas. Tal es el caso de las especies contenidas en el género Ocimum, que han sido utilizadas tanto con fines culinarios como curativos. Además, reportes farmacológicos señalan que tienen efecto sobre el sistema cardiovascular, son fuente de agentes antioxidantes e incluso se les ha demostrado que inhiben enzimas relacionadas con la HTA, como la enzima convertidora de angII (ECA). Objetivo general: Demostrar el efecto antihipertensivo de Ocimum basilicum, Ocimum selloi y del ácido rosmarínico, y su potencial efecto sobre las comorbilidades asociadas; daño a órgano blanco, inflamación, déficit cognitivo y estrés conductual. Materiales y métodos: Con hojas secas de O. basilicum y O. selloi se obtuvieron dos extractos etanólicos (60%) que fueron separados con acetato de etilo (fracciones de O. basilicum (Ob-AEt) y O. selloi: Os-AEt). Dado que ambas contienen ácido rosmarínico (AR), este compuesto se utilizó como referencia. Se utilizaron ratones ICR (n=12; 35 g. NOM-062-ZOO-1999). El modelo de hipertensión consistió en la administración de angII (0.2 μg/Kg ip n=12 por grupo) durante 12 semanas. En la semana 6 se inició la administración de los tratamientos; vehículo (tween20 1%), telmisartán (10 mg/Kg), diazepam (0.25 mg/Kg), galantamina (0.2 mg/Kg), Ob-AEt (25 mg/Kg), Os-AEt (25 mg/Kg) y AR (0.39, 0.78, 1.56, 3.12 y 6.24 mg/Kg). La PA se midió a las 0, 6 y 12 semanas del experimento. Posteriormente los animales se sometieron a pruebas conductuales: laberinto acuático de Morris (LAM; memoria,), laberinto elevado en cruz (LEC; ansiedad), campo abierto (CA; coordinación motora). Al finalizar las pruebas conductuales se sacrificaron por dislocación cervical para obtener: cerebro y riñones para cuantificación de citocinas, y muestras sanguíneas para la cuantificación corticosterona (ELISA) y MPE (citometría de flujo). Resultados: En el presente trabajo, la administración de angII a 0.2 μg/kg ip durante 12 semanas activó la respuesta inflamatoria mediada por citocinas, principalmente por IL1β, IL6, TNFα y la quimiocina MCP1; a su vez disminuyó la actividad de citocinas antinflamatorias como IL4, IL10 y TGFβ. La angII provocó hipertensión y ansiedad, actuando sobre receptores AT1 distribuidos a lo largo del eje hipotálamo-pituitaria-adrenal (HPA), incrementando los niveles de corticosterona. Al observar el comportamiento de los animales en los diferentes modelos conductuales, se observó un efecto ansiogénico en el grupo que recibió vehículo, presentando disminución en el número de entradas y tiempo en brazos abiertos (NA y TA) en el LEC. Este efecto fue contrarrestado de forma dosis-dependiente con AR: Emáx=63.69%, DE50=0.23 mg/Kg, para NA; Emáx=59.17 %, DE50=0.15 mg/Kg para TA. Al administrar Oba-AEt y Ose-AEt, y algunas dosis de AR, el daño causado por angII se detuvo al restablecer los niveles de corticosterona sérica y disminuir las citocinas proinflamatorias y MCP-1. Ob-AEt, Os-AEt y AR protegieron contra el incremento en el estrés tangencial vascular (shear stress) generado por angII, ya que se observó un decremento significativo de las poblaciones de MPE AnexinaV+ /CD105+ /CD31+ y AnexinaV+ /CD105+ /CD1046+ . Conclusión: En el presente trabajo se reporta que los extractos obtenidos a partir de O. basilicum y O. selloi poseen efecto antiinflamatorio (cerebral y renal), antihipertensivo, ansiolítico, nootrópico, no modifican la conducta motora, además, previenen la disfunción endotelial generada por la administración crónica de angII. El abordaje de la HTA es y será siempre multidisciplinario. La necesidad de controlar la PA, así como la inhibición de las acciones de la angII continúa siendo uno de los objetivos primordiales en la terapéutica cardiovascular, que intenta controlar las consecuencias a largo plazo de la HTA, lo que ha planteado una interesante evolución hacia la prevención en estos pacientes de alto riesgo, mediante el desarrollo de nuevos medicamentos, dispositivos y procedimientos que están diseñados para tratar la hipertensión y sus comorbilidades

Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice

Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG) ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects

The Potential Neuroprotective Effect of Cyperus esculentus L. Extract in Scopolamine-Induced Cognitive Impairment in Rats: Extensive Biological and Metabolomics Approaches

The aim of the present study is to investigate the phytochemical composition of tiger nut (TN) (Cyperus esculentus L.) and its neuroprotective potential in scopolamine (Scop)-induced cognitive impairment in rats. The UHPLC-ESI-QTOF-MS analysis enabled the putative annotation of 88 metabolites, such as saccharides, amino acids, organic acids, fatty acids, phenolic compounds and flavonoids. Treatment with TN extract restored Scop-induced learning and memory impairments. In parallel, TN extract succeeded in lowering amyloid beta, -secretase protein expression and acetylcholine esterase (AChE) activity in the hippocampus of rats. TN extract decreased malondialdehyde levels, restored antioxidant levels and reduced proinflammatory cytokines as well as the Bax/Bcl2 ratio. Histopathological analysis demonstrated marked neuroprotection in TN-treated groups. In conclusion, the present study reveals that TN extract attenuates Scop-induced memory impairments by diminishing amyloid beta aggregates, as well as its anti-inflammatory, antioxidant, anti-apoptotic and anti-AChE activities.Ministry of Science and Innovation, Spain (MICINN) Spanish Government FJC2020-044298-

Nutrition for Brain Development

High-quality primary data publications and review articles have been selected for publication in this Special Issue. They, collectively, draw a comprehensive picture of some of the most relevant questions linking (healthy) nutrition to brain development and brain disorders

Chronic supplementation with a mix of salvia officinalis and salvia lavandulaefolia improves morris water maze learning in normal adult C57Bl/6J mice

Background: Two different species of sage, Salvia officinalis and Salvia lavandulaefolia, have demonstrated activities in cognitive function during preclinical and clinical studies related to impaired health situations or single administration. Different memory processes have been described to be significantly and positively impacted. Objective: Our objective is to explore the potential of these Salvia, and their additional activities, in healthy situations, and during prolonged administration, on memory and subsequent mechanisms of action related to putative effects. Design: This mouse study has implicated four investigational arms dedicated to control, Salvia officinalis aqueous extract, Salvia lavandulaefolia-encapsulated essential oil and a mix thereof (Cognivia™) for 2 weeks of administration. Cognitive functions have been assessed throughout Y-maze and Morris water maze models. The impact of supplementation on lipid peroxidation, oxidative stress, neurogenesis, neuronal activity, neurotrophins, neurotrophin receptors, CaM kinase II and glucocorticoid receptors has been assessed via post-interventional tissue collection. Results: All Salvia groups had a significant effect on Y-maze markers on day 1 of administration. Only the mix of two Salvia species demonstrated significant improvements in Morris water maze markers at the end of administration. Considering all biological and histological markers, we did not observe any significant effect of S. officinalis, S. lavandulaefolia and a mix of Salvia supplementation on lipid peroxidation, oxidative stress and neuronal plasticity (neurogenesis, neuronal activity, neurotrophins). Interestingly, CaM kinase II protein expression is significantly increased in animals supplemented with Salvia. Conclusion: The activities of Salvia alone after one intake have been confirmed; however, a particular combination of different types of Salvia have been shown to improve memory and present specific synergistic effects after chronic administration in healthy mice

Traditional used Plants against Cognitive Decline and Alzheimer Disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory deficits, impaired cognitive function, and altered and inappropriate behavior. Aging represents the most important risk factor for AD and the global trend in the phenomenon of population aging has dramatic consequences for public health, healthcare financing, and delivery systems in the word and, especially in developing countries. Mounting evidence obtained in in vitro and in vivo studies, suggests that various traditionally used plants in Asia, India, and Europe significantly affect key metabolic alterations culminating in AD-typical neurodegeneration. The present article aims to bring the reader up-to-date on the most recent studies and advances describing the direct and indirect activities of traditional used plants and its constituents possibly relieving features of AD. A variety of traditional used plants and its extracts exerted activities on AD related drug targets including AChE activity, antioxidative activity, modulation of Aβ-producing secretase activities, Aβ-degradation, heavy metal chelating, induction of neurotrophic factors, and cell death mechanisms. Although pre-clinical investigations identified promising drug candidates for AD, clinical evidences are still pending

What can traditional Chinese medicine do for adult neurogenesis?

Adult neurogenesis plays a crucial role in cognitive function and mood regulation, while aberrant adult neurogenesis contributes to various neurological and psychiatric diseases. With a better understanding of the significance of adult neurogenesis, the demand for improving adult neurogenesis is increasing. More and more research has shown that traditional Chinese medicine (TCM), including TCM prescriptions (TCMPs), Chinese herbal medicine, and bioactive components, has unique advantages in treating neurological and psychiatric diseases by regulating adult neurogenesis at various stages, including proliferation, differentiation, and maturation. In this review, we summarize the progress of TCM in improving adult neurogenesis and the key possible mechanisms by which TCM may benefit it. Finally, we suggest the possible strategies of TCM to improve adult neurogenesis in the treatment of neuropsychiatric disorders