scholarly journals Herba houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 164
Author(s):  
Ke Cao ◽  
Weiqiang Lv ◽  
Xuyun Liu ◽  
Yingying Fan ◽  
Kexin Wang ◽  
...  
Keyword(s):  
Adenosine Monophosphate ◽  
Poloxamer 407 ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Complex Activities

Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

Beneficial Effect of Flavone Derivatives on Aβ-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α

2015 ◽  
Vol 34 (3) ◽  
pp. 274-283 ◽  
Author(s):  
Farshad Arsalandeh ◽  
Shahin Ahmadian ◽  
Forough Foolad ◽  
Fariba Khodagholi ◽  
Mahdi M. Farimani ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1

In the present study, the neuroprotective effect of 5-hydroxy-6,7,4′-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4′-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aβ)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aβ injection. Seven days after Aβ administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.

scholarly journals GATA3 controls mitochondrial biogenesis in primary human CD4+ T cells during DNA damage

2019 ◽  
Author(s):  
Lauren A. Callender ◽  
Johannes Schroth ◽  
Elizabeth C. Carroll ◽  
Lisa E.L. Romano ◽  
Eleanor Hendy ◽  
...  
Keyword(s):  
Dna Damage ◽  
T Cells ◽  
T Cell ◽  
Cell Manipulation ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Damage Repair ◽  
Superoxide Dismutase 3 ◽  
Amp Activated Protein Kinase

Introductory paragraphGATA binding protein 3 (GATA3) has traditionally been regarded as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper (Th) 2 cells. However, increasing evidence shows that GATA3 is involved in a myriad of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. We show here a previously unknown mechanism utilized by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the binding of GATA3, AMP-activated protein kinase (AMPK), peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α), nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 3 (SOD3) to the DNA damage repair (DDR) component ATR. These findings extend the pleotropic nature of GATA3 and highlight the potential for GATA3-targeted cell manipulation for clinical interventions.

scholarly journals Pentoxifylline Enhances Antioxidative Capability and Promotes Mitochondrial Biogenesis in D-Galactose-Induced Aging Mice by Increasing Nrf2 and PGC-1α through the cAMP-CREB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Yu Wang ◽  
Tianyun Zhang ◽  
Hui Zhao ◽  
Chunxiao Qi ◽  
Xiaoming Ji ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Mitochondrial Biogenesis ◽  
Phosphodiesterase Inhibitor ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Mitochondrial Ultrastructure ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antioxidant Genes ◽  
Creb Pathway

Aging is a complex phenomenon associated with oxidative stress and mitochondrial dysfunction. The objective of this study was to investigate the potential ameliorative effects of the phosphodiesterase inhibitor pentoxifylline (PTX) on the aging process and its underlying mechanisms. We treated D-galactose- (D-gal-) induced aging mice with PTX and measured the changes in behavior, degree of oxidative damage, and mitochondrial ultrastructure and content as well as the expression of nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant genes and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha- (PGC-1α-) dependent mitochondrial biogenesis genes. The results demonstrated that PTX improved cognitive deficits, reduced oxidative damage, ameliorated abnormal mitochondrial ultrastructure, increased mitochondrial content and Nrf2 activation, and upregulated antioxidant and mitochondrial biogenesis gene expression in the hippocampus of wild-type aging mice. However, the above antiaging effects of PTX were obviously decreased in the brains of Nrf2-deficient D-gal-induced aging mice. Moreover, in hydrogen peroxide-treated SH-SY5Y cells, we found that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and Nrf2/PGC-1α act in a linear way by CREB siRNA transfection. Thus, PTX administration improved the aging-related decline in brain function by enhancing antioxidative capability and promoting mitochondrial biogenesis, which might depend on increasing Nrf2 and PGC-1α by activating the cAMP-CREB pathway.

scholarly journals GDF15 Mediates the Metabolic Effects of PPARβ/δ by Activating AMPK

2020 ◽  
Author(s):  
David Aguilar-Recarte ◽  
Emma Barroso ◽  
Javier Pizarro-Delgado ◽  
Lucía Peña ◽  
Maria Ruart ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Ampk Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Growth Differentiation Factor 15 ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Amp Activated Protein Kinase

Abstract Peroxisome proliferator-activated receptor β/δ(PPARβ/δ) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examined whether the beneficial effects of PPARβ/δ activation depended on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARβ/δ activation increased GDF15 levels and ameliorated glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, inflammation and activated AMPK in HFD-fed mice, whereas these effects were abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15-/- mice. The AMPK-p53 pathway was involved in the PPARβ/δ-mediated increase in GDF15, which in turn activated again AMPK. Finally, Gdf15-/- mice showed reduced AMPK activation in skeletal muscle, whereas GDF15 administration resulted in AMPK activation in this organ. Collectively, these data reveal a novel mechanism by which PPARβ/δ activation increases the levels of GDF15 via AMPK and p53, which in turn mediates the metabolic effects of PPARβ/δ by sustaining AMPK activation.

scholarly journals 1,5-Anhydro-D-Fructose Protects against Rotenone-Induced Neuronal Damage In Vitro Through Mitochondrial Biogenesis

2021 ◽  
Vol 22 (18) ◽  
pp. 9941
Author(s):  
Yuki Kasamo ◽  
Kiyoshi Kikuchi ◽  
Munekazu Yamakuchi ◽  
Shotaro Otsuka ◽  
Seiya Takada ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ampk Phosphorylation ◽  
Amp Activated Protein Kinase

Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson’s disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

scholarly journals From Exercise to Cognitive Performance: Role of Irisin

2021 ◽  
Vol 11 (15) ◽  
pp. 7120
Author(s):  
Mirko Pesce ◽  
Irene La Fratta ◽  
Teresa Paolucci ◽  
Alfredo Grilli ◽  
Antonia Patruno ◽  
...  
Keyword(s):  
The Elderly ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
General Exercise ◽  
Fibronectin Type Iii ◽  
Exercise Induced ◽  
Fibronectin Type Iii Domain ◽  
The Brain

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.

scholarly journals BST204 Protects Dexamethasone-Induced Myotube Atrophy through the Upregulation of Myotube Formation and Mitochondrial Function

2021 ◽  
Vol 18 (5) ◽  
pp. 2367
Author(s):  
Ryuni Kim ◽  
Hyebeen Kim ◽  
Minju Im ◽  
Sun Kyu Park ◽  
Hae Jung Han ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Inflammatory Responses ◽  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dry Extract ◽  
Myotube Formation ◽  
Species Production

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.

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