Plasma protein binding of polyphenols from maritime pine bark extract (USP)

Kurlbaum, Max; Högger, Petra

doi:10.1016/j.jpba.2010.07.038

Cited by 40 publications

(19 citation statements)

References 38 publications

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“…The protein concentration determined in human plasma was 150-fold higher than in DMEM which suggested that the adsorption of polyphenols to plasma proteins contributed to their enhanced stability in this matrix. The degree of plasma protein binding has been shown to be highly variable among individual polyphenolic compounds, 44 and it needs to be investigated how strong the extent of protein binding correlates with the compounds' stability in plasma or cell culture medium.…”

Section: ■ Discussionmentioning

confidence: 99%

Stability of Dietary Polyphenols under the Cell Culture Conditions: Avoiding Erroneous Conclusions

Xiao

Högger

2015

J. Agric. Food Chem.

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133

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Most data of bioactivity from dietary polyphenols have been derived from in vitro cell culture experiments. In this context, little attention is paid to potential artifacts due to chemical instability of these natural antioxidants. An early degradation time ((C)T10) and half-degradation time ((C)T50) were defined to characterize the stability of 53 natural antioxidants incubated in Dulbecco's modified Eagle's medium (DMEM) at 37 °C. The degree of hydroxylation of flavones and flavonols significantly influenced the stability in order resorcinol-type > catechol-type > pyrogallol-type, with the pyrogallol-type being least stable. In contrast, any glycosylation of polyphenols obviously enhanced their stability. However, the glycosylation was less important compared to the substitution pattern of the nucleus rings. Methoxylation of flavonoids with more than three hydroxyl groups typically improved their stability as did the hydrogenation of the C2═C3 double bond of flavonoids to corresponding flavanoids. There was no significant correlation between the antioxidant potential of polyphenols and their stability. Notably, the polyphenols were clearly more stable in human plasma than in DMEM, which may be caused by polyphenol-protein interactions. It is strongly suggested to carry out stability tests in parallel with cell culture experiments for dietary antioxidants with catechol or pyrogallol structures and pyrogallol-type glycosides in order to avoid artifacts.

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Section: ■ Discussionmentioning

confidence: 99%

Stability of Dietary Polyphenols under the Cell Culture Conditions: Avoiding Erroneous Conclusions

Xiao

Högger

2015

J. Agric. Food Chem.

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133

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“…In addition to its abundance in edible plants, PCA can be generated by the interconversion of other types of phenolic compounds via the metabolism in intestinal microflora (Vitaglione et al, 2007). PCA shows a relatively low plasma protein binding (20.7 Ϯ 0.09% to human albumin) (Kurlbaum and Högger, 2011), and several types of PCA metabolites after methylation, glucuronidation, and glycine conjugation were found in rats after in vivo infusion (Cao et al, 2009). It is also known that dehydroxylation and decarboxylation of PCA occur by the gut micro-organisms (Dacre and Williams, 1968).…”

Section: Discussionmentioning

confidence: 99%

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Kim

Bae

Lim

et al. 2012

J Pharmacol Exp Ther

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Bleeding is the most common and serious adverse effect of currently available antiplatelet drugs. Many efforts are being made to develop novel antithrombotic agents without bleeding risks. Shear stress-induced platelet aggregation (SIPA), which occurs under abnormally high shear stress, plays a crucial role in the development of arterial thrombotic diseases. Here, we demonstrate that protocatechuic acid (PCA), a bioactive phytochemical from Lonicera (honeysuckle) flowers, selectively and potently inhibits high shear (Ͼ10,000 s Ϫ1 )-induced platelet aggregation. In isolated human platelets, PCA decreased SIPA and attenuated accompanying platelet activation, including intracellular calcium mobilization, granule secretion, and adhesion receptor expression. The anti-SIPA effect of PCA was mediated through blockade of von Willebrand factor binding to activated glycoprotein Ib, a primary and initial event for the accomplishment of SIPA. Conspicuously, PCA did not inhibit platelet aggregation induced by other endogenous agonists like collagen, thrombin, or ADP that are important in both pathological thrombosis and normal hemostasis. Antithrombotic effects of PCA were confirmed in vivo in a rat arterial thrombosis model, where PCA significantly delayed the arterial occlusion induced by FeCl 3 . Of particular note, PCA did not increase bleeding times in a rat tail transection model, whereas conventional antiplatelet drugs, aspirin, and clopidogrel substantially prolonged it. Collectively, these results suggest that PCA may be a novel antiplatelet agent that can prevent thrombosis without increasing bleeding risks.

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“…The plasma contained a mixture of 1.3 µM caffeic acid, 80 µM ferulic acid, 6 µM taxifolin and 6 µM metabolite M1. The chosen concentrations were based on analytical considerations and previously also used for determination of plasma protein binding of these compounds [16]. In parallel a control was prepared containing the polyphenols in 3.5 mL plasma without erythrocytes.…”

Section: Methodsmentioning

confidence: 99%

“…We recently analyzed the plasma protein binding of various maritime pine bark polyphenols and observed pronounced differences in the binding tendency [16]. While catechin and taxifolin displayed protein binding close to 100%, low binding around 30% was seen for M1 and its structurally related metabolite M2 (δ-(3-methoxy-4-hydroxy-phenyl)-γ-valerolactone).…”

Section: Introductionmentioning

confidence: 99%

Facilitated Uptake of a Bioactive Metabolite of Maritime Pine Bark Extract (Pycnogenol) into Human Erythrocytes

2013

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Many plant secondary metabolites exhibit some degree of biological activity in humans. It is a common observation that individual plant-derived compounds in vivo are present in the nanomolar concentration range at which they usually fail to display measurable activity in vitro. While it is debatable that compounds detected in plasma are not the key effectors of bioactivity, an alternative hypothesis may take into consideration that measurable concentrations also reside in compartments other than plasma. We analysed the binding of constituents and the metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone (M1), that had been previously detected in plasma samples of human consumers of pine bark extract Pycnogenol, to human erythrocytes. We found that caffeic acid, taxifolin, and ferulic acid passively bind to red blood cells, but only the bioactive metabolite M1 revealed pronounced accumulation. The partitioning of M1 into erythrocytes was significantly diminished at higher concentrations of M1 and in the presence of glucose, suggesting a facilitated transport of M1 via GLUT-1 transporter. This concept was further supported by structural similarities between the natural substrate α-D-glucose and the S-isomer of M1. After cellular uptake, M1 underwent further metabolism by conjugation with glutathione. We present strong indication for a transporter-mediated accumulation of a flavonoid metabolite in human erythrocytes and subsequent formation of a novel glutathione adduct. The physiologic role of the adduct remains to be elucidated.

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Plasma protein binding of polyphenols from maritime pine bark extract (USP)

Cited by 40 publications

References 38 publications

Stability of Dietary Polyphenols under the Cell Culture Conditions: Avoiding Erroneous Conclusions

Stability of Dietary Polyphenols under the Cell Culture Conditions: Avoiding Erroneous Conclusions

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Facilitated Uptake of a Bioactive Metabolite of Maritime Pine Bark Extract (Pycnogenol) into Human Erythrocytes

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