Metabolic benefits of inhibiting cAMP-PDEs with resveratrol

Chung, Jay H.

doi:10.4161/adip.21158

Cited by 30 publications

(23 citation statements)

References 39 publications

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“…In NHEKs treated for 16 hours with 50 µM RSV, we observed phosphorylation signalling events such as increased phosphorylation of pyruvate dehydrogenase E1 component subunit alpha (PDE1) at serine 293 (Fig. S7a), an effect known to inhibit endogenous pyruvate breakdown and oxidative phosphorylation 47 . Consequently, this molecular effect led to increased intracellular levels of the potential ROS-scavenger pyruvate while lactate remained at constant levels ( Figure 5a).…”

Section: Oxidative Products Of Rsv Induce a Reduced Cellular Redox Enmentioning

confidence: 99%

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Plauth

Geikowski

Cichon

et al. 2016

Preprint

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ABSTRACT:Resveratrol has gained tremendous interest owing to multiple reported healthbeneficial effects. However, the underlying key mechanism of action of resveratrol remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to the generation of oxidation products such as reactive oxygen species (ROS). At low hormetic concentrations (< 50 µM), treatment with resveratrol increased cell viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, application of resveratrol led to mild, Nrf2-specific cellular gene expression reprogramming. For example, in 2 primary human epidermal keratinocytes this resulted in a 1.3-fold increase of endogenous metabolites such as glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein.After external application of oxidative stress by using 0.8% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells.In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that effects from resveratrol treatment are essentially based on oxidative triggering of cells. In relevant physiological microenvironments this effect can lead to hormetic shifting of cellular defence towards a more reductive state to improve resilience to oxidative stress in a manner that can be exactly defined by the redox-environment of the cell.

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Section: Oxidative Products Of Rsv Induce a Reduced Cellular Redox Enmentioning

confidence: 99%

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Plauth

Geikowski

Cichon

et al. 2016

Preprint

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“…Resveratrol isolated from grapes is present in the red wine and has been shown to modify cognition through the PDE-4-cAMP metabolic pathway [14]. Caffeine (1,3,5-trimethylxanthine), widely consumed as coffee in the world, targets both PDE subtypes 4 and 5 (PDE-4, PDE-5) and adenosine-2 receptor [15].…”

Section: Introductionmentioning

confidence: 99%

Proof‐of‐Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase‐4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

Chiu

Gericke²,

Farina-Woodbury

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer's dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

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“…BIOMOL Green, which is used for calculation of the amount of phosphate released, was purchased from Funakoshi Co. PDE activity was measured using a cyclic nucleotide PDE assay kit from Enzo Life Sciences (BML-AK800) according to the manufacturer's instructions, except that PDE 100 mU per well were used. [24][25][26] Stock solutions of inhibitors were prepared as 100 mM in DMSO and diluted to the appropriate concentrations. In the assay, 1 μL of each inhibitor solution was added before the addition of PDE enzyme solution.…”

Section: Analysesmentioning

confidence: 99%

Synthesis of glycosides of resveratrol, pterostilbene, and piceatannol, and their anti-oxidant, anti-allergic, and neuroprotective activities

Sato

Shimizu

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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Resveratrol was glucosylated to its 3- and 4′-β-glucosides by cultured cells of Phytolacca americana. On the other hand, cultured P. americana cells glucosylated pterostilbene to its 4′-β-glucoside. P. americana cells converted piceatannol into its 4′-β-glucoside. The 3- and 4′-β-glucosides of resveratrol were further glucosylated to 3- and 4′-β-maltosides of resveratrol, 4′-β-maltoside of which is a new compound, by cyclodextrin glucanotransferase. Resveratrol 3-β-glucoside and 3-β-maltoside showed low 2,2-diphenyl-1-picrylhydrazyl free-radical-scavenging activity, whereas other glucosides had no radical-scavenging activity. Piceatannol 4′-β-glucoside showed the strongest inhibitory activity among the stilbene glycosides towards histamine release from rat peritoneal mast cells. Pterostilbene 4′-β-glucoside showed high phosphodiesterase inhibitory activity.

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Metabolic benefits of inhibiting cAMP-PDEs with resveratrol

Cited by 30 publications

References 39 publications

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Proof‐of‐Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase‐4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

Synthesis of glycosides of resveratrol, pterostilbene, and piceatannol, and their anti-oxidant, anti-allergic, and neuroprotective activities

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