Inhibition of Cyclic Adenosine Monophosphate-Specific Phosphodiesterase by Various Food Plant-Derived Phytotherapeutic Agents

Röhrig, Teresa; Pacjuk, Olga; Hernández-Huguet, Silvia; Körner, Johanna; Scherer, Katharina M.; Richling, Elke

doi:10.3390/medicines4040080

Cited by 18 publications

(12 citation statements)

References 74 publications

(117 reference statements)

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“…In addition, Röhrig and coworkers tested the following polyphenol-rich extracts on PDE isolated from the lung tumor xenograft cell line LXFL529L: artichoke (Cynara scolymus) extract, which had a significant inhibitory influence on PDE activity (IC 50 = 0.9 ± 0.1 mg/mL); the flavones luteolin (IC 50 = 41 ± 10 µM) and 3,4-dicaffeoylquinic acid (IC 50 > 1.0 mM), and strawberry tree fruit (Arbutus unedo) extract, which showed no inhibitory effect on PDE at levels below 5 mg/mL. A plausible explanation for the lack of inhibition by the strawberry tree extract could be low AC content [25], as strawberry tree fruit has an AC content of only 0.51 mg per 100 g of fresh fruit [30].…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The inhibitory effect of each extract on PDE 3B was measured according to the method published by Pöch et al [34] with slight modifications [25,32]. One hundred microliters (100 µL) of the sample and 20 µL of PDE 3B (200 Units/mL) were incubated for 15 min at 4 • C. Afterwards, a 50 µL volume of cAMP Mix (30 mM Tris/HCl pH 7.4, 9 mM MgCl 2 , 3 mM 5 AMP, 3 µM cAMP, 2.6 µCi/mL [2,8-3 H]-cAMP) was added and the mixture incubated for 25 min at 37 • C to allow for reaction.…”

Section: The Camp-specific Pde Activity Assaymentioning

confidence: 99%

“…For example, caffeine was already recognized as a nonspecific inhibitor at the time of PDE discovery [20,21]. In addition, some classes of flavonoids (flavonols, flavones, ACs, flavanones, and flavanols) have shown PDE-inhibiting potential in several test systems [13,14,[22][23][24][25]. The inhibitory effects of polyphenol-rich foods on PDE inhibition was demonstrated by inhibition of human cGMP-specific PDEs using red wine and grape skin extracts; this experiment was conducted using COS-7 cells that expressed the full-length cDNA of PDE 5A1 [26].…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins

Göttel

Niesen

Daub

et al. 2020

IJMS

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Phosphodiesterases (PDEs) are essential enzymes for the regulation of pathways mediated by cyclic adenosine monophosphate (cAMP). Secondary plant compounds like anthocyanins (ACs) can inhibit PDE activity and, consequently, may be beneficial for lipid metabolism. This study investigated 18 AC-rich juice extracts and pure reference compounds from red fruits for potential inhibitory effects on PDE 3B activity. Extracts were obtained through adsorption on Amberlite® XAD 7 resin. Based on this screening, the chokeberry, blueberry, pomegranate, and cranberry extracts were active, with half maximal inhibitory concentrations (IC50) ranging from 163 ± 3 µg/mL to 180 ± 3 µg/mL. The ACs in these extracts, peonidin-3-glucoside and cyanidin-3-arabinoside, were the most active single compounds (IC50 = 56 ± 20 µg/mL, 108 ± 6 µg/mL). All extracts comprised high amounts of phenolic compounds, as determined by the Folin–Ciocalteu assay, ranging from 39.8 ± 1.5 to 73.5 ± 4.8 g gallic acid equivalents (GAE)/100 g extract. Pomegranate and chokeberry extracts exhibited the largest amounts of polyphenols (72.3 ± 0.7 g GAE/100 g, 70.6 ± 4.1 g GAE/100 g, respectively). Overall, our results showed that fruit juice extracts and their ACs can inhibit PDE activity. Any potential health benefits in vivo will be investigated in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Camp-specific Pde Activity Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins

Göttel

Niesen

Daub

et al. 2020

IJMS

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“…It should be pointed out that caffeine also functions as a PDE inhibitor (Rohrig et al, 2017), which increases cAMP concentration and PKA activation at cellular level. Therefore, we cannot completely exclude the possibility that caffeine-induced enhancement of SOCE may be partially attributed to SR Ca 2+ load-independent pathway, e.g., PKA-dependent activation.…”

Section: Discussionmentioning

confidence: 99%

Potential Arrhythmogenic Role of TRPC Channels and Store-Operated Calcium Entry Mechanism in Mouse Ventricular Myocytes

et al. 2018

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Background and Purpose: Store-operated calcium entry (SOCE) is an important physiological phenomenon that extensively mediates intracellular calcium ion (Ca2+) load. It has been previously found in myocytes isolated from neonatal or diseased hearts. We aimed to determine its existence, molecular nature in undiseased hearts and its potential arrhythmogenic implications under hyperactive conditions.Experimental Approach: Ventricular myocytes isolated from adult FVB mice were studied by using Ca2+ imaging and whole-cell perforated patch-clamp recording. In addition, lead II ECGs were recorded in isolated Langendorff-perfused mice hearts. Functional TRPC channel antibodies and inhibitors, and TRPC6 activator hyperforin were used.Key Results: In this study, we demonstrate the existence and contribution of SOCE in normal adult mouse cardiac myocytes. For an apparent SOCE activation, complete depletion of sarcoplasmic reticulum (SR) Ca2+ by employing both caffeine (10 mM) and thapsigargin (1 μM) or cyclopiazonic acid (10 μM) was required. Consistent with the notion that SOCE may be mediated by heteromultimeric TRPC channels, SOCEs observed from those myocytes were significantly reduced by the pretreatment with anti-TRPC1, 3, and 6 antibodies as well as by gadolinium, a non-selective TRPC channel blocker. In addition, we showed that SOCE may regulate spontaneous SR Ca2+ release, Ca2+ waves, and triggered activities which may manifest cardiac arrhythmias. Since the spontaneous depolarization in membrane potential preceded the elevation of intracellular Ca2+, an inward membrane current presumably via TRPC channels was considered as the predominant cause of cellular arrhythmias. The selective TRPC6 activator hyperforin (0.1–10 μM) significantly facilitated the SOCE, SOCE-mediated inward current, and calcium load in the ventricular myocytes. ECG recording further demonstrated the proarrhythmic effects of hyperforin in ex vivo mouse hearts.Conclusion and Implications: We suggest that SOCE, which is at least partially mediated by TRPC channels, exists in adult mouse ventricular myocytes. TRPC channels and SOCE mechanism may be involved in cardiac arrhythmogenesis via promotion of spontaneous Ca2+ waves and triggered activities under hyperactivated conditions.

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Acute Treatment with the Nootropic CILTEP® Does Not Improve Cognitive Performance in Healthy Middle-Aged Participants

Possemis,

Caldenhove,

Sambeth

et al. 2024

J Cogn Enhanc

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This study investigated the acute effects of the dietary nootropic stack CILTEP®. It contains a combination of ingredients that have been individually reported to improve cognitive performance. Especially, the ingredients luteolin, which is considered a phosphodiesterase type 4 (PDE4) inhibitor, and forskolin, an adenylate cyclase stimulator, were of interest since they can increase the second messenger cAMP and thus also intracellular signaling. Numerous studies have shown that inhibition of PDE4 can improve memory in animals and humans. We examined whether acute dosing of 3 capsules of CILTEP® would improve cognitive function in healthy participants aged 30 to 40 (n = 33). We used a randomized, double-blind, placebo-controlled, two-way cross-over design. Our test battery was aimed at measuring memory performance, attention, and sensorimotor speed. The primary outcome measures were the performance on the verbal learning task and the spatial pattern separation task. Secondary outcomes included other cognitive tests, event-related potentials (ERPs), and assessment of the activity of the enzyme beta-glucuronidase and its effect on the bioavailability of luteolin, heart rate, and blood pressure. No relevant effects of acute CILTEP® treatment were found on any measure of the test battery or ERPs. Blood plasma concentrations of luteolin increased, yet about 2000 times too low to likely exert any PDE4 inhibition. CILTEP® treatment did neither affect heart rate nor blood pressure. In summary, there is no evidence that a single standardized dose of 3 capsules of CILTEP® can improve cognitive function in healthy middle-aged participants.

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Inhibition of Cyclic Adenosine Monophosphate-Specific Phosphodiesterase by Various Food Plant-Derived Phytotherapeutic Agents

Cited by 18 publications

References 74 publications

In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins

In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins

Potential Arrhythmogenic Role of TRPC Channels and Store-Operated Calcium Entry Mechanism in Mouse Ventricular Myocytes

Acute Treatment with the Nootropic CILTEP® Does Not Improve Cognitive Performance in Healthy Middle-Aged Participants

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