Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of .

A water extract of the Ayurvedic plant (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer's disease and affects dendritic arborization, mitochondrial activity, and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW, although little is known about how interactions between these compounds contribute to the plant's therapeutic benefit.

Peripheral Blood DNA Methylation Changes in Response to Treatment in Aged Mice.

Alterations in epigenetic modifications, like DNA methylation, in peripheral blood could serve as a useful, minimally invasive biomarker of the effects of anti-aging interventions. This study explores this potential with a water extract of the botanical (CAW). Eighteen-month-old mice were treated with CAW in their drinking water for 5 weeks alongside vehicle-treated eighteen-month-old C57BL6 mice.

Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis.

(L.) Urban (family Apiaceae) () is a traditional botanical medicine used in aging and dementia. Water extracts of (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health.

Quantifying Withanolides in Plasma: Pharmacokinetic Studies and Analytical Methods.

(common name: ashwagandha; WS) is an Ayurvedic botanical that has become popular for its reputed effects on stress and insomnia. Research into the bioactive compounds responsible for the biological effects of WS has largely focused on withanolides, a group of steroidal lactones commonly found in the Solanaceae family. Until recently, however, it was unclear which, if any, withanolides were present in the plasma after the ingestion of WS products.

Multi-omics analysis in mouse primary cortical neurons reveals complex positive and negative biological interactions between constituent compounds in Centella asiatica.

Background: A water extract of the Ayurvedic plant (CAW) improves cognitive function in mouse models of aging and Alzheimer's disease, and affects dendritic arborization, mitochondrial activity and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW although little is known about how interactions between these compounds contribute to the plant's therapeutic benefit.

Methods: Mouse primary cortical neurons were treated with CAW, or equivalent concentrations of four TT combined, eight CQA combined, or these twelve compounds combined (TTCQA).

(Ashwagandha) Improves Spatial Memory, Anxiety and Depressive-like Behavior in the 5xFAD Mouse Model of Alzheimer's Disease.

(WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in . Here, we sought to confirm these effects in the 5xFAD mouse model of β-amyloid (Aβ) accumulation.

Liquid chromatography-mass spectrometry quantification of phytochemicals in using data-dependent acquisition, multiple-reaction-monitoring, and parallel-reaction-monitoring with an inclusion list.

Characterization of botanical extracts by mass spectrometry-based metabolomics analysis helps in determining the phytochemical composition that underlies their bioactivity and potential health benefits, while also supporting reproducibility of effects in clinical trials. The quantification of seven withanolides in using three mass-spectrometry methods was evaluated using Deming regression. Two high-resolution time-of-flight mass spectrometry methods were used, one operating in data-dependent acquisition mode and the other in parallel-reaction-monitoring mode with an inclusion list.

and its caffeoylquinic acid and triterpene constituents increase dendritic arborization of mouse primary hippocampal neurons and improve age-related locomotion deficits in .

Introduction: (CA) is known in Ayurvedic medicine as a rejuvenating herb with particular benefits in the nervous system. Two groups of specialized metabolites found in CA and purported to contribute to its beneficial effects are triterpenes (TTs) and caffeoylquinic acids (CQAs). In order to evaluate the role and interactions of TTs and CQAs in the effects of CA, we examined the neurotrophic effects of a water extract of CA (CAW) and combinations of its TT and CQA components in mouse primary hippocampal neurons and in flies .

Amelioration of age-related cognitive decline and anxiety in mice by extract varies by sex, dose and mode of administration.

A water extract (CAW) of the Ayurvedic plant administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.

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.

Amelioration of age-related cognitive decline and anxiety in mice by extract varies by sex, dose and mode of administration.

We have previously reported that a water extract (CAW) of the Ayurvedic plant administered in drinking water can improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here we compared the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.

Centella asiatica promotes antioxidant gene expression and mitochondrial oxidative respiration in experimental autoimmune encephalomyelitis.

Centella asiatica (Centella) is a traditional botanical medicine that shows promise in treating dementia based on behavioral alterations seen in animal models of aging and cognitive dysfunction. In order to determine if Centella could similarly improve cognitive function and reduce disease burden in multiple sclerosis (MS), we tested its effects in the neuroinflammatory experimental autoimmune encephalomyelitis (EAE) model of MS. In two independent experiments, C57BL/6J mice were treated following induction of EAE with either a standardized water extract of Centella (CAW) or placebo for 2 weeks.

Quantification of Caffeoylquinic Acids and Triterpenes as Targeted Bioactive Compounds of in Extracts and Formulations by Liquid Chromatography Mass Spectrometry.

(CA) is a culinary vegetable and well-known functional food that is widely used as a medicinal herb and dietary supplement. CA is rich in pentacyclic triterpenes (TTs), including asiaticoside (AS), madecassoside (MS) and the related aglycones asiatic acid (AA), madecassic acid (MA). Traditionally, TTs have been associated with the bioactivity and health promoting effect of CA.

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Extracts That Mediate Resilience to Chronic Stress in .

Common symptoms of depressive disorders include anhedonia, sleep problems, and reduced physical activity. Drugs used to treat depression mostly aim to increase serotonin signaling but these can have unwanted side effects. Depression has also been treated by traditional medicine using plants like (CA) and this has been found to be well tolerated.

Bioanalytical method validation and application to a phase 1, double-blind, randomized pharmacokinetic trial of a standardized (L.) Urban water extract product in healthy older adults.

is an herbaceous plant reputed in Eastern medicine to improve memory. Preclinical studies have shown that aqueous extract (CAW) improves neuronal health, reduces oxidative stress, and positively impacts learning and cognition. This study aimed to develop and validate bioanalytical methods for detecting known bioactive compounds from in human biological matrices and apply them to a human pharmacokinetic trial in healthy older adults.

Recovery of motor function is associated with rescue of glutamate biomarkers in the striatum and motor cortex following treatment with Mucuna pruriens in a murine model of Parkinsons disease.

There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). Mucuna pruriens has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of Mucuna pruriens, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase (TH) protein expression in the nigrostriatal pathway, or glutamate biomarkers in both the striatum and motor cortex.

Perspective: Council for Responsible Nutrition Science in Session. Optimizing Health with Nutrition-Opportunities, Gaps, and the Future.

Achieving optimal health is an aspirational goal for the population, yet the definition of health remains unclear. The role of nutrition in health has evolved beyond correcting malnutrition and specific deficiencies and has begun to focus more on achieving and maintaining 'optimal' health through nutrition. As such, the Council for Responsible Nutrition held its October 2022 Science in Session conference to advance this concept.

Extracts Promote Resilience against Age-Related and Stress-Induced Behavioral Phenotypes in a Possible Role of Other Compounds besides Withanolides.

(WS) extracts have been used in traditional medicine for millennia to promote healthy aging and wellbeing. WS is now also widely used in Western countries as a nutritional supplement to extend healthspan and increase resilience against age-related changes, including sleep deficits and depression. Although human trials have supported beneficial effects of WS, the study designs have varied widely.

Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial.

is reputed in Eastern medicine to improve cognitive function in humans. Preclinical studies have demonstrated that aqueous extracts of improve cognition in mouse models of aging and Alzheimer's disease (AD) through the modulation of mitochondrial biogenesis and nuclear factor-erythroid-2-related factor 2 (-dependent antioxidant response genes. This randomized, double-blind, crossover Phase I trial explored the oral bioavailability and pharmacokinetics of key compounds from two doses (2 g and 4 g) of a standardized aqueous extract product (CAP), over 10 h, in four mildly demented older adults on cholinesterase inhibitor therapy.

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.

Effects of (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia.

Background: Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in worldwide usage due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders.