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

Abstract

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.

Fractionation of Extracts from Black Chokeberry, Cranberry, and Pomegranate to Identify Compounds That Influence Lipid Metabolism

“…Within the last years, it has been reported that polyphenols can influence the lipid metabolism in vitro and in vivo [ 8 , 16 , 38 , 39 ]. In our previous work, extracts from red fruit juices or concentrates like cranberry, red grape, or blueberry have proven to be potent inhibitors of the enzyme PDE 3B [ 28 ]. To identify fruit juice constituents which influence lipid metabolism, a fractionation of the three most potent extracts from chokeberry, cranberry, and pomegranate was performed, and the effects of the anthocyanin, copigment, and polymer fractions in three different in vitro assays (lipid accumulation, lipolysis, and PDE 3B activity) were investigated.…”

“…Some in vitro studies have also examined the effects of polyphenol-rich extracts on lipid metabolism, as well as one of our previous studies [ 20 , 28 , 41 ]. Kowalska et al revealed that a berry fruit extract obtained from chokeberry, raspberry, bilberry, and cranberry fruits ( c = 25–100 µg/mL) significantly decreased lipid accumulation in 3T3-L1 cells without showing cytotoxicity [ 21 ].…”

“…We identified cyanidin-3-glucoside in the anthocyanin fractions of chokeberry, cranberry, and pomegranate extracts and observed inhibitory activities of these fractions towards PDE 3B. In addition, in our earlier study, it was demonstrated that peonidin-3-glucoside, cyanidin-3-arabinoside, and cyanidin-3-glucoside could inhibit PDE 3B activity with IC 50 values between 120 ± 44 µM and 299 ± 56 µM [ 28 ]. In this study, we identified these anthocyanins in the anthocyanin fractions of chokeberry, cranberry, and pomegranate extracts and confirmed that the anthocyanin fractions are potent inhibitors of the enzyme PDE 3B.…”

“…Little has been published regarding the influence of these compounds on PDE inhibition. However, in our earlier study, pomegranate extracts, in which pedunculagin and punicalagin were identified as the major copigments, were already found to be potent inhibitors of the enzyme PDE 3B [ 28 ].…”

“…The inhibitory effect of each fraction and subfraction on cAMP-specific PDE 3B was measured according to the method published by Pöch et al [ 27 ] with slight modifications [ 28 ]. Briefly, 100 µL of the sample (five concentrations depending on the inhibition strength) and 20 µL of PDE 3B (200 Units/mL) were incubated for 15 min at 4 °C.…”