Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration.

Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis.

Can dietary patterns prevent cognitive impairment and reduce Alzheimer's disease risk: Exploring the underlying mechanisms of effects.

Alzheimer's disease (AD) is one of the fastest growing cognitive decline-related neurological diseases. To date, effective curative strategies have remained elusive. A growing body of evidence indicates that dietary patterns have significant effects on cognitive function and the risk of developing AD.

Characterizing brain metabolic function ex vivo with acute mouse slice punches.

Mitochondrial dysfunction and metabolic reprogramming are implicated in a variety of neurological disorders. Here, we present a protocol that enables complex profiling of brain metabolic function using acute mouse brain slices . Utilizing differential metabolic conditions, substrates, and inhibitors, this protocol can be broadly applied to determine metabolic shift or reprogramming upon genetic manipulations, pathological insults, or therapeutic interventions and could thus further the understanding of the dynamic role of energy metabolism in brain physiological function and diseases.

ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism.

Alzheimer's disease (AD) risk gene ApoE4 perturbs brain lipid homeostasis and energy transduction. However, the cell-type-specific mechanism of ApoE4 in modulating brain lipid metabolism is unclear. Here, we describe a detrimental role of ApoE4 in regulating fatty acid (FA) metabolism across neuron and astrocyte in tandem with their distinctive mitochondrial phenotypes.

Mitochondria-Targeted Therapeutics for Alzheimer's Disease: The Good, the Bad, the Potential.

Alzheimer's disease (AD) is the leading cause of dementia. Thus far, 99.6% of clinical trials, including those targeting energy metabolism, have failed to exert disease-modifying efficacy.

Cellular Specificity and Inter-cellular Coordination in the Brain Bioenergetic System: Implications for Aging and Neurodegeneration.

As an organ with a highly heterogenous cellular composition, the brain has a bioenergetic system that is more complex than peripheral tissues. Such complexities are not only due to the diverse bioenergetic phenotypes of a variety of cell types that differentially contribute to the metabolic profile of the brain, but also originate from the bidirectional metabolic communications and coupling across cell types. While brain energy metabolism and mitochondrial function have been extensively investigated in aging and age-associated neurodegenerative disorders, the role of various cell types and their inter-cellular communications in regulating brain metabolic and synaptic functions remains elusive.

Nobiletin Protects against Systemic Inflammation-Stimulated Memory Impairment via MAPK and NF-κB Signaling Pathways.

Neuroinflammation has been intensively demonstrated to be related to various neurodegenerative diseases including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). A natural polymethoxylated flavone, nobiletin (NOB) has been reported to alleviate oxidative stress, insulin resistance, and obesity. In this study, we evaluated the protection effects of NOB on neuroinflammation and memory deficit.

Tea polyphenols direct Bmal1-driven ameliorating of the redox imbalance and mitochondrial dysfunction in hepatocytes.

Circadian rhythms are intimately linked to cellular redox status homeostasis via the regulation of mitochondrial function. Tea polyphenols (TP) are nutraceuticals that possess powerful antioxidant properties, especially ameliorating oxidative stress. The objective of this study was to investigate whether circadian clock is involved in the protection effect of TP on oxidative stress cell models.

EGCG stimulates the recruitment of brite adipocytes, suppresses adipogenesis and counteracts TNF-α-triggered insulin resistance in adipocytes.

The global rise in obesity and type 2 diabetes has precipitated the need for therapeutic intervention in the arsenal against adiposity. (-)-Epigallocatechin-3-gallate (EGCG), a major nutraceutical component of green tea, has been regarded as a nutraceutical that has powerful antioxidant and anti-obesity bioactivities. In the present study, we showed that EGCG alleviates intracellular lipid accumulation markedly, and the inhibitory effect was largely limited to the early stage of adipocyte differentiation.

Nobiletin protects against insulin resistance and disorders of lipid metabolism by reprogramming of circadian clock in hepatocytes.

Scope: Circadian clock plays a principal role in orchestrating our daily physiology and metabolism, and their perturbation can evoke metabolic diseases such as fatty liver and insulin resistance. Nobiletin (NOB) has been demonstrated to possess antitumor and neuroprotective activities. The objective of the current study is to determine potential effects of NOB on modulating the core clock gene Bmal1 regarding ameliorating glucolipid metabolic disorders.

EGCG evokes Nrf2 nuclear translocation and dampens PTP1B expression to ameliorate metabolic misalignment under insulin resistance condition.

As a major nutraceutical component of green tea (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists due to its well-documented antioxidant and antiobesity bioactivities. In the current study, we aimed to investigate the protective effect of EGCG on metabolic misalignment and in balancing the redox status in mice liver and HepG2 cells under insulin resistance condition. Our results indicated that EGCG accelerates the glucose uptake and evokes IRS-1/Akt/GLUT2 signaling pathway via dampening the expression of protein tyrosine phosphatase 1B (PTP1B).

1,3-Dichloro-2-propanol evokes inflammation and apoptosis in BV-2 microglia via MAPKs and NF-κB signaling pathways mediated by reactive oxygen species.

1,3-dichloro-2-propanol (1,3-DCP) is a widely concerned food processing contaminant which has been investigated for decades. While the neurotoxicity of 1,3-DCP and related mechanisms are still elusive. Herein, the effect of 1,3-DCP on neurotoxicity was investigated using BV-2 microglia cells.

Neuroprotective action of tea polyphenols on oxidative stress-induced apoptosis through the activation of the TrkB/CREB/BDNF pathway and Keap1/Nrf2 signaling pathway in SH-SY5Y cells and mice brain.

Many studies have shown that oxidative stress is a major cause of cellular injuries in a variety of human diseases including cognitive impairment. Tea polyphenols (TPs), natural plant flavonoids found in tea plant leaves, possess the bioactivity to affect the pathogenesis of several chronic diseases via antioxidant associated mechanisms. However, the possible antioxidant and neuroprotective properties of TPs in the brain of mice housed in constant darkness and in HO-stimulated SH-SY5Y cells are yet to be elucidated.

Tea polyphenols ameliorates neural redox imbalance and mitochondrial dysfunction via mechanisms linking the key circadian regular Bmal1.

Circadian rhythms are autonomous anticipatory oscillators that control a large array of physiological and metabolic processes. Compelling evidence points toward an interplay between circadian rhythms and cellular redox metabolism. Dysregulation of circadian rhythms is associated with neurodegenerative diseases and accelerated aging.

(-)-Epigallocatechin-3-gallate Ameliorates Insulin Resistance and Mitochondrial Dysfunction in HepG2 Cells: Involvement of Bmal1.

Scope: Normal physiological processes require a robust biological timer called the circadian clock. Dysregulation of circadian rhythms contributes to a variety of metabolic syndrome, including obesity and insulin resistance. (-)-Epigallocatechin-3-gallate (EGCG) has been demonstrated to possess antioxidant, anti-inflammatory, and cardioprotective bioactivities.

EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.

Obesity, which is caused by an energy imbalance between calorie intake and consumption, has become a major international health burden. Obesity increases the risk of insulin resistance and age-related cognitive decline, accompanied by peripheral inflammation. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, possesses antioxidant, anti-inflammatory, and cardioprotective activities; however, few reports have focused on its potential effect on cognitive disorders.

Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells.

Athyrium multidentatum (Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties.

EGCG ameliorates diet-induced metabolic syndrome associating with the circadian clock.

In response to the daily light-dark (LD) cycle, organisms on Earth have evolved with the approximately 24-h endogenous oscillations to coordinate behavioral and physiological processes, including feeding, sleep, and metabolism homeostasis. Circadian desynchrony triggered by an energy-dense diet rich in fats and fructose is intimately connected with a series of metabolic disorders. Previous studies revealed that (-)-Epigallocatechin-3-gallate (EGCG) could mitigate metabolic misalignment; however, only a few reports have focused on its potential effect on directly manipulating circadian rhythms to ameliorate metabolic syndrome.

Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy.

Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner.

Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways.

Momordin Ic is a principal saponin constituent of Fructus Kochiae, which acts as an edible and pharmaceutical product more than 2000 years in China. Our previous research found momordin Ic induced apoptosis by PI3K/Akt and MAPK signaling pathways in HepG2 cells. While the role of autophagy in momordin Ic induced cell death has not been discussed, and the connection between the apoptosis and autophagy is not clear yet.

Nutrient values and bioactivities of the extracts from three fern species in China: a comparative assessment.

Pteridium aquilinum, Osmunda cinnamomea Linn, and Athyrium multidentatum (Doll.) Ching are three fern species widely consumed as potherbs and traditional medicinal herbs in China. Nevertheless, no detailed comparative assessments of their nutrient values and bioactivities have been reported.