Mode of administration influences plasma levels of active compounds in 5xFAD mice while markers of neuroinflammation remain unaltered.

Introduction: A water extract of (L.) Urban [Apiaceae] (CAW) has demonstrated cognitive-enhancing effects in mouse models of Alzheimer's disease and aging, the magnitude of which is influenced by whether CAW is delivered in the drinking water or the diet. These cognitive benefits are accompanied by improvements in oxidative stress and mitochondrial function in the brain, two pathways related to the neuroinflammatory response.

Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-β Toxicity.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of () that protect against Aβ cytotoxicity in vitro. has been associated with improving mental health and cognitive function, with potential use in Alzheimer's disease.

Developing a Rational, Optimized Product of for Examination in Clinical Trials: Real World Challenges.

Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active components and biological targets. Translation away from preclinical models, and developing an optimized, reproducible botanical product for use in clinical trials, presents particular challenges for phytotherapeutic agents compared to single chemical entities.

and Extracts Ameliorate Behavioral Deficits in an In Vivo Model of Oxidative Stress.

Due to an increase in the aging population, age-related diseases and age-related changes, such as diminished cognition and sleep disturbances, are an increasing health threat. It has been suggested that an increase in oxidative stress underlies many of these changes. Current treatments for these diseases and changes either have low efficacy or have deleterious side effects preventing long-time use.

Alters Metabolic Pathways Associated With Alzheimer's Disease in the 5xFAD Mouse Model of -Amyloid Accumulation.

is an herb used in Ayurvedic and traditional Chinese medicine for its beneficial effects on brain health and cognition. Our group has previously shown that a water extract of (CAW) elicits cognitive-enhancing effects in animal models of aging and Alzheimer's disease, including a dose-related effect of CAW on memory in the 5xFAD mouse model of -amyloid accumulation. Here, we endeavor to elucidate the mechanisms underlying the effects of CAW in the brain by conducting a metabolomic analysis of cortical tissue from 5xFAD mice treated with increasing concentrations of CAW.

The Impact of the hAPP695SW Transgene and Associated Amyloid-β Accumulation on Murine Hippocampal Biochemical Pathways.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ) peptide in the brain.

Objective: To gain a better insight into alterations in major biochemical pathways underlying AD.

Methods: We compared metabolomic profiles of hippocampal tissue of 20-month-old female Tg2576 mice expressing the familial AD-associated hAPP695SW transgene with their 20-month-old wild type female littermates.

Vesicular glutamate transporter 2-containing neurons of the centrally-projecting Edinger-Westphal nucleus regulate alcohol drinking and body temperature.

Previous studies in rodents have repeatedly demonstrated that the centrally-projecting Edinger-Westphal nucleus (EWcp) is highly sensitive to alcohol and is also involved in regulating alcohol intake and body temperature. Historically, the EWcp has been known as the main site of Urocortin 1 (Ucn1) expression, a corticotropin-releasing factor-related peptide, in the brain. However, the EWcp also contains other populations of neurons, including neurons that express the vesicular glutamate transporter 2 (Vglut2).

Social Housing Leads to Increased Ethanol Intake in Male Mice Housed in Environmentally Enriched Cages.

An individual's social environment affects alcohol intake. However, the complex interactions between social context and alcohol intake remain understudied in preclinical models. In the present study, we sought to characterize the effects of social housing on voluntary ethanol intake in male C567BL/6J mice using a continuous access two-bottle choice model.

Prolonged Treatment with Centella asiatica Improves Memory, Reduces Amyloid-β Pathology, and Activates NRF2-Regulated Antioxidant Response Pathway in 5xFAD Mice.

Background: The medicinal herb Centella asiatica has been long been used for its neuroprotective and cognitive enhancing effects. We have previously shown that two weeks of treatment with a water extract of Centella asiatica (CAW) improves cognition and activates the endogenous antioxidant response pathway without altering amyloid-β (Aβ) plaque burden.

Objective: Here, we assess the effect of long-term treatment of CAW in the 5xFAD mouse model of Aβ accumulation.

Manifestations of domination: Assessments of social dominance in rodents.

Social hierarchies are ubiquitous features of virtually all animal groups. The varying social ranks of members within these groups have profound effects on both physical and emotional health, with lower-ranked individuals typically being the most adversely affected by their respective ranks. Thus, reliable measures of social dominance in preclinical rodent models are necessary to better understand the effects of an individual's social rank on other behaviors and physiological processes.

Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging.

The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months.

Temporal analysis of individual ethanol consumption in socially housed mice and the effects of oxytocin.

Rationale: The majority of preclinical studies assessing treatments for alcohol use disorder use singly housed animals. Because social factors affect ethanol intake, studies investigating such treatments in group-housed animals are needed.

Objectives: We investigated the effects of repeated oxytocin treatment on ethanol intake in socially housed male and female C57BL/6J mice.

Caffeoylquinic Acids in Reverse Cognitive Deficits in Male 5XFAD Alzheimer's Disease Model Mice.

(CA) is an edible plant and a popular botanical dietary supplement. It is reputed, in Ayurveda, to mitigate age-related cognitive decline. There is a considerable body of preclinical literature supporting CA's ability to improve learning and memory.

Integration of mass spectral fingerprinting analysis with precursor ion (MS1) quantification for the characterisation of botanical extracts: application to extracts of Centella asiatica (L.) Urban.

Introduction: The phytochemical composition of plant material governs the bioactivity and potential health benefits as well as the outcomes and reproducibility of laboratory studies and clinical trials.

Objective: The objective of this work was to develop an efficient method for the in-depth characterisation of plant extracts and quantification of marker compounds that can be potentially used for subsequent product integrity studies. Centella asiatica (L.

Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology.

Background:Environmental copper has been implicated in the pathogenesis of Alzheimer’s disease based on evidence that: 1) brain copper levels increase with age, 2) copper promotes misfolding and toxicity of amyloid-β in vitro, 3) copper-modulating interventions reduce amyloid pathology in animal models. However, the effect of copper upon non-amyloid Alzheimer’s pathology is relatively under-explored.Objective:To determine if modulation of brain copper level affects brain tau pathology and/or associated cognitive impairment.

Loss of NRF2 leads to impaired mitochondrial function, decreased synaptic density and exacerbated age-related cognitive deficits.

Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) regulates cellular bioenergetics and improves neuronal health in aging. Yet how NRF2 participates in maintaining synaptic, mitochondrial and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects neuronal metabolism, synaptic density and cognitive performance in aged mice.

Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice.

(CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer's disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.

triterpenes for diabetic neuropathy: a randomized, double-blind, placebo-controlled, pilot clinical study.

Background: Diabetic neuropathy (DN), a common complication of diabetes mellitus, results from hyperglycemia, poor microcirculation and attendant nerve damage. Currently available treatments relieve symptoms, but do not modify the neurodegeneration underlying DN. (CA) triterpenes improved microcirculation in earlier clinical studies, and showed neurotropic effects in preclinical models suggesting a potential disease modifying effect in DN.

Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice.

Centella asiatica is a medicinal plant used to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates β-amyloid (Aβ)-induced spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its in vivo mechanism of improving Aβ-related cognitive impairment.

Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice.

Introduction: Centella asiatica is a plant used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates age-related spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its mechanism of improving age-related cognitive impairment.

Attenuates Mitochondrial Dysfunction and Oxidative Stress in A-Exposed Hippocampal Neurons.

has been used for centuries to enhance memory. We have previously shown that a water extract of (CAW) protects against the deleterious effects of amyloid- (A) in neuroblastoma cells and attenuates A-induced cognitive deficits in mice. Yet, the neuroprotective mechanism of CAW has yet to be thoroughly explored in neurons from these animals.

Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.

The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer's disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons.