P henolic acid pharmacokinetics and modulation of vascular smooth muscle cells following Montmorency...
1
Phenolic acid pharmacokinetics and modulation of vascular smooth muscle cells following Montmorency tart cherry (L. Prunus Cerasus) intake Karen M. Keane 1 , Phillip G. Bell 1 , John K. Lodge 2 , Costas L. Constantinou 2 , Sarah E. Jenkinson 2 , Rosemary Bass 2 and Glyn Howatson 1 1 Department of Sport, Exercise and Rehabilitation 2 Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, NE1 8ST. CONCLUSIONS • This profile showed that both hydroxybenzoic acids (PCA and VA) are most bioavailable in plasma 1-2 h post MC consumption, whilst other hydroxycinnamic acid (CHL) were not present in plasma. • The combination of PCA and VA increased cell migration of VSMC. • These data may be useful for the design and interpretation of intervention studies investigating the health effects of MC polyphenols. • A diet rich in plant foods is inversely correlated with cardiovascular morbidity and mortality. • The main non–flavonoid polyphenols of dietary significance are phenolic acids. Tart Montmorency cherries (MC) are a functional food of growing interest and have been shown to be high in numerous phytonutrients(1) • Despite previous studies in cell culture and animal models, where cherry extracts have been shown to exert a range of cardio-protective effects, there has been only one study illustrating the pharmaco-kinetics of tart cherry phytochemicals and concurrent evidence of a biologic effect(2). • Aim: to examine 1) the time-course of selected phenolic compounds following ingestion of MC 2) their subsequent influence on cell behaviour in vitro. • Twelve healthy males (mean ± SD age, stature, mass and BMI was 26 ± 3 years, 178.5 ± 7.6 cm, 85.2 ± 11.7 kg and 26.7 ± 3.2 kg/m 2 , respectively) volunteered to participate. • Participants were randomly assigned to either a high (60 mL) or low (30 mL) MC group in a double blind, crossover design. • Venous blood samples were taken 0 and 1, 2, 3, 5 and 8 h post consumption. Plasma concentrations of protocatechuic (PCA), vanillic (VA) and chlorogenic acid (CHL) were analysed by reversed – phase high performance liquid chromatography with diode array and mass spectrometry detection. INTRODUCTION METHODS 0 50 100 150 200 Ethanol PCA VA PCA/VA # % M igration RESULTS TACN TPC TEAC Total CHL * Total PCA * Total VA * 30 mL MC 34.71 ± 0.17 79.30± 0.72 0.331± 0.01 0.205± 0.24 0.020± 0.11 0.253± 0.84 60 mL MC 69.42 ± 0.35 158.59 ± 1.43 0.662± 0.03 0.410± 0.48 0.040± 0.22 0.506± 1.68 Frozen cherries 0.03 ± 0.0009 0.005± 0.0004 0.002± 0.0002 - - - Dried cherries 0.008 ± 0.0003 0.006± 0.0005 0.002± 0.0001 - - - Table 1: Estimated total anthocyanins, phenolics and antioxidant activity in pitted, frozen, whole, dried and concentrated Montmorency tart cherry. TACN, total anthocyanins; TPC, total phenolic content; TEAC, trolox equivalent antioxidant capacity. n = 6 per analysis, (*n=3). 0 1 2 3 5 8 0.0 0.1 0.2 0.3 0.4 Tim e (hours) V A (µg/m L) Figure 1. Plasma phenolic metabolites. (a) protocatechuic acid; (b) vanillic acid. 60mL = 60 mL of MC concentrate; 30 mL = 30 mL of MC concentrate diluted with 100 mL of water. N = 12 per dose. • Concentration(c) max values for individual phenolic compounds were not significant between doses. • AUC values for individual phenolic acids were also not significantly different between doses. • 60mL MC dose, the time (t) max was 1h for PCA and VA. • 30mL dose, t max differed by compound detected, occurring at 1 h for PCA and 2 h for VA. Figure 2: Migration of human vascular smooth muscle cells in vitro in response to metabolites PCA (32µM) and VA (4µM) compared to ethanol only control, over 24hours. N = 3. # indicates a significant difference between condition (p<0.05). (a) (b) @KarenKeane4 uk.linkedin.com/pub/karen- keane [email protected] k REFERENCES 1 Wang H, Nair MG, Strasburg GM, et al. Antioxidant and Antiinflammatory Activities of Anthocyanins and Their Aglycon, Cyanidin, from Tart Cherries. J Nat Prod 1999;62(2):294-6. 2 Seymour ME, Warber, SM, Kirakosyan A, Noon KR, et al. Anthocyanin pharmacokinetics and dose – dependent plasma antioxdant pharmacodynamics folloing whole tart cherry intake in healthy humans. J Funct Foods 2014; 11: 509 – 516. 0.0 1.0 2.0 3.0 4.0 60 m L 30 m L P C A (µg/m L) 2 nd year
-
Upload
hester-crawford -
Category
Documents
-
view
216 -
download
2
Transcript of P henolic acid pharmacokinetics and modulation of vascular smooth muscle cells following Montmorency...
Phenolic acid pharmacokinetics and modulation of vascular smooth muscle cells following Montmorency tart cherry (L. Prunus Cerasus) intakeKaren M. Keane1, Phillip G. Bell1, John K. Lodge2, Costas L. Constantinou2, Sarah E. Jenkinson2, Rosemary Bass2 and Glyn Howatson1
1Department of Sport, Exercise and Rehabilitation 2 Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, NE1 8ST.
CONCLUSIONS• This profile showed that both hydroxybenzoic acids
(PCA and VA) are most bioavailable in plasma 1-2 h post MC consumption, whilst other hydroxycinnamic acid (CHL) were not present in plasma.
• The combination of PCA and VA increased cell migration of VSMC.
• These data may be useful for the design and interpretation of intervention studies investigating the health effects of MC polyphenols.
• A diet rich in plant foods is inversely correlated with cardiovascular morbidity and mortality.
• The main non–flavonoid polyphenols of dietary significance are phenolic acids. Tart Montmorency cherries (MC) are a functional food of growing interest and have been shown to be high in numerous phytonutrients(1)
• Despite previous studies in cell culture and animal models, where cherry extracts have been shown to exert a range of cardio-protective effects, there has been only one study illustrating the pharmaco-kinetics of tart cherry phytochemicals and concurrent evidence of a biologic effect(2).
• Aim: to examine 1) the time-course of selected phenolic compounds following ingestion of MC 2) their subsequent influence on cell behaviour in vitro.
• Twelve healthy males (mean ± SD age, stature, mass and BMI was 26 ± 3 years, 178.5 ± 7.6 cm, 85.2 ± 11.7 kg and 26.7 ± 3.2 kg/m2, respectively) volunteered to participate.
• Participants were randomly assigned to either a high (60 mL) or low (30 mL) MC group in a double blind, crossover design.
• Venous blood samples were taken 0 and 1, 2, 3, 5 and 8 h post consumption. Plasma concentrations of protocatechuic (PCA), vanillic (VA) and chlorogenic acid (CHL) were analysed by reversed – phase high performance liquid chromatography with diode array and mass spectrometry detection.
• Vascular smooth muscle cell (VSMC) migration was also assessed in vitro.
• Data are presented as mean ± SEM.
INTRODUCTION
METHODS
0
50
100
150
200EthanolPCAVAPCA/VA
#
% M
igra
tio
n
RESULTS
TACN TPC TEAC Total CHL*
Total PCA*
Total VA*
30 mL MC 34.71 ± 0.17
79.30± 0.72
0.331± 0.01
0.205± 0.24
0.020± 0.11
0.253± 0.84
60 mL MC 69.42 ± 0.35
158.59± 1.43
0.662± 0.03
0.410± 0.48
0.040± 0.22
0.506± 1.68
Frozen cherries
0.03 ± 0.0009
0.005± 0.0004
0.002± 0.0002
- - -
Dried cherries
0.008 ± 0.0003
0.006± 0.0005
0.002± 0.0001
- - -
Table 1: Estimated total anthocyanins, phenolics and antioxidant activity in pitted, frozen, whole, dried and concentrated Montmorency tart cherry.
TACN, total anthocyanins; TPC, total phenolic content; TEAC, trolox equivalent antioxidant capacity. n = 6 per analysis, (*n=3).
0 1 2 3 5 80.0
0.1
0.2
0.3
0.4
Time (hours)
VA
(µ
g/m
L)
Figure 1. Plasma phenolic metabolites. (a) protocatechuic acid; (b) vanillic acid. 60mL = 60 mL of MC concentrate; 30 mL = 30 mL of MC concentrate diluted with 100 mL of water. N = 12 per dose.
• Concentration(c)max values for individual phenolic compounds were not significant between doses. • AUC values for individual phenolic acids were also not significantly different between doses.• 60mL MC dose, the time (t)max was 1h for PCA and VA. • 30mL dose, tmax differed by compound detected, occurring at 1 h for PCA and 2 h for VA.
Figure 2: Migration of human vascular smooth muscle cells in vitro in response to metabolites PCA (32µM) and VA (4µM) compared to ethanol only control, over 24hours. N = 3. # indicates a significant difference between condition (p<0.05).
(a)
(b)
@KarenKeane4 uk.linkedin.com/pub/karen-keane [email protected]
REFERENCES
1 Wang H, Nair MG, Strasburg GM, et al. Antioxidant and Antiinflammatory Activities of Anthocyanins and Their Aglycon, Cyanidin, from Tart Cherries. J Nat Prod 1999;62(2):294-6.2 Seymour ME, Warber, SM, Kirakosyan A, Noon KR, et al. Anthocyanin pharmacokinetics and dose – dependent plasma antioxdant pharmacodynamics folloing whole tart cherry intake in healthy humans. J Funct Foods 2014; 11: 509 – 516.
0.0
1.0
2.0
3.0
4.0
60 mL
30 mL
PC
A (
µg
/mL
)
2nd year
