Cardiovascular-protective properties of plant polyphenols

Epidemiological evidence suggests strongly that consumption of fruit and vegetables is associated with a reduced risk of cancer and cardiovascular disease. There is evidence that the polyphenol content of fruit and vegetables contribute to these protective effects. This study examines the antioxidant properties and effects of a range of plant extract polyphenols (PEP) on endothelial fiinction and platelet aggregation, examining the PEP ability to scavenge superoxide and increase nitric oxide bioavailability. A crude raspberry extract (RE) containing a mixture of polyphenols, a raspberry extract that had been processed through an artificial digestive system (GR), 2 purified polyphenols---quercetin-3'-sulphate (QS) and quercetin-3-glucuronide (QG) were examined together with ascorbic acid (AA) as a positive control. The scavenging capacity of PEP for superoxide (O2- ) generated from xanthine/xanthine oxidase, and for the elevated levels of O2- from arteries of female stroke prone spontaneously hypertensive rats (SHRSP), was measured by lucigenin chemiluminescence. Nitric oxide bioavailability was measured mainly in carotid artery rings from SHRSP but some studies were carried out using its normotensive control the Wister Kyoto Rat (WKY). It was expressed as the increase in contractile responses to phenylephrine in the presence of the nitric oxide synthase inhibitor L-NAME. ADP dependent platelet aggregation was measured in an agrogometer in plasma from healthy human volunteers in the presence and absence of PEP. Differences between groups were compared by t-test with Bonferoni correction, n = 4-10/ group for all studies. EC50 values for scavenging O2- by PEP when O2- was generated by xanthine/ xanthine oxidase were as follows with 95% confidence intervals in brackets (ranked in order of potency highest to least potent); QG 0.012 mug/ml (0.006-0.022), GR 0.012 mug/ml (0.0055-0.024), RE 0.026) mug/ml (0.012-0.059), QS 0.047 mug/ml (0.020-0.103) and AA 0.192 (0.089-0.415). In contrast to scavenging O2- generated by xanthine/xanthine oxidase, the PEP showed no scavenging effect on the elevated O2- levels in arteries of SHRSP. All PEP showed the ability to increase NO bioavailability in SHRSP; no effect was seen in the control WKY. RE was able to increase NO bioavailability in SHRSP (over the concentration range 90-0.36 mug/ml). QG and QS improved NO bioavailability at 50mug/ml (100mumol/l) and 12mug/ml (31mumol/l) respectively. QG and QS were found to increase NO bioavailability at even lower concentrations when given in combination; QG 0.3mug/ml (6 mumol/l) and QS 0.5mug/ml (1mumol/l) when combined. RE at 100 mug/ml was the only PEP to show a significant inhibitory effect on platelet aggregation. In conclusion the PEP have been found to scavenge O2- and improve endothelium function but results suggest they have less effect on platelet aggregation. RE appeared to be the most potent but the active ingredients still have to be fully identified and their in vivo bioavailability confirmed. In contrast QS and QG have been identified in plasma and are strong candidates to contribute to the cardiovascular protective effects of fruit and vegetables. Discrepancies between the PEP's ability to scavenge O2- and improve NO bioavailability suggest that mechanisms in addition to O2- scavenging may contribute to cardiovascular protective effects of PEP