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Leucoselect® Phytosome®
Bioavailable standardized Grape seed procyanidins for the cardiovascular system

Antioxidant compounds such as polyphenols have been recognized to prevent degenerative processes related to chronic diseases. Polyphenols, commonly found in fruits and vegetables, are a key element of the Mediterranean diet, and have long been known for their capillary protective effects. Their beneficial effect for cardiovascular health has been demonstrated by scientific studies and clinical trials(1).
In recent years, researchers have focused specifically on the therapeutic potential of the phenolic compounds found in grapes. Interesting findings originated from epidemiology, in particular the observation that red wine (very rich in polyphenols) could exert a preventive action against the development of chronic diseases of the cardiovascular system, like atherosclerosis, a disease strictly related to oxidative damage to plasma lipoproteins(3).
This could explain, at least in part, the so-called “French paradox”, a term referring to the lower-than-expected incidence of cardiovascular diseases in France despite the high dietary saturated fat intake and the habit of smoking cigarettes(3,4).
Grape seed extracts have been demonstrated of particular clinical interest(5), due to the presence of small molecular size polyphenols, named oligomeric procyanidins (OPCs). However, grape seeds extracts have variable chemical compositions, and polyphenols are known for their low and erratic bioavailability(6-8).

 

Please note that this web site is not aimed at consumers as the information herein contained does not make reference to finished products. Please note this website is accessible from various countries all over the world and hence it may contain statements or product classification not applicable to your country. The claims made are in reference to ingredients only, hence they do not refer to finished products and they may not comply with Regulation 1924/2006/CE. The marketer of any finished product containing any ingredient is responsible for assuring that the destination of the product and the claims made for the finished product are lawful and comply with all applicable laws and regulations of the country or countries in which the product is to be sold.

 

A natural clinically-proven aid for cardiovascular protection

Leucoselect® is a grape seed extract with a well-defined chemical composition, which was elucidated by HPLC-UV, GPC and HPLC-TSP-MS as follows(9):

This high content of smaller size OPCs is crucial for the therapeutic activity, since the absorption of procyanidins is critically dependent on their molecular weight(10). In the production of Leucoselect®, high molecular weight procyanidins are discarded, and the more active oligomer like  dimers, trimers, tetramers and their gallates are concentrated.

To further improve their bioavailability, Leucoselect® has been complexed with soy (non-GMO) phospholipids (1:3 w/w), thus generating Leucoselect® Phytosome®.

The cardiovascular protecting activity of this product is supported by four clinical trials(11-14),  both in normal and pathological conditions, and by extensive pharmacological data(15-24).

Clinical studies

The efficacy of Leucoselect® Phytosome® was assessed at a dosage corresponding to 300 mg/day of procyanidins in four clinical trials. It was proven effective in improving antioxidant defences and in counteracting the oxidative stress, both in normal and in pathological circumstances characterized by an increase in oxidant generation and a decrease in antioxidant protection.

Improvement of the total antioxidant capacity of plasma in healthy volunteers(11)

Leucoselect® Phytosome® was administered for 5 days to 20 young subjects in a single-blind randomized placebo-controlled crossover trial.
The product induced a significant increase of serum total antioxidant capacity (TRAP) assessed on day 1 and day 5, starting already from 30 min postdose with a further increase at 60 min postdose, in comparison with baseline values. After a washout period of at least 2 weeks, the treatment was repeated with similar results.
Antioxidant defenses protect low-density lipoproteins (LDLs) from oxidation by free radicals, a process associated with the initiation of atherosclerosis

Effect of Leucoselect® Phytosome® on TRAP in healthy volunteers improvement

Improvement of plasma oxidative status in healthy volunteers after a fatty meal(12)

The capacity of Leucoselect® Phytosome® to prevent the plasma oxidative stress after a fatty meal, rich in lipidic peroxides (“Milanese” steak and French fries), has been evaluated in 8 healthy volunteers. At the beginning of the trial the subjects received the lipidic peroxides rich meal and after a week the same meal and Leucoselect® Phytosome®.
The product was proven able to reduce the oxidative stress induced by the meal, providing a significant reduction of plasma postprandial lipid hydroperoxide concentration with an increase of TRAP and resistance of LDLs to oxidative modification.
Leucoselect® Phytosome® is able to prevent plasma postprandial oxidative stress.
It decreases the oxidants, increases the antioxidant levels in plasma and enhances the resistance of LDLs to oxidative modification.

Effect of Leucoselect® Phytosome® on mean plasma postprandial lipid hydroperoxide concentration

Reduction of LDL susceptibility to oxidative stress in heavy smokers(13)

Leucoselect® Phytosome® was administered for 4 weeks to 24 healthy male heavy smokers, aged 50 or more, in a randomized double-blind crossover trial. The product induced a significant improvement of LDL resistance to oxidation, as shown by lipid peroxidation parameters: thiobarbituric acid reactive substances concentration (TBARS, an index of lipid peroxidation and oxidative stress) was significantly reduced while the lag phase (an index of LDL resistance to oxidation) was prolonged, both in comparison with placebo and basal values.
Leucoselect® Phytosome® was also endowed with a significant efficacy in what is probably the common model of oxidative stress, namely smoking.
Cigarette smoke contains carbon and oxygen-centered free radicals, which can directly initiate and propagate the process of lipid peroxidation.

Effect of Leucoselect® Phytosome® on LDL resistance to oxidation in heavy smokers

Improvement of oxidative stress in diabetic patients(14)

In a double-blinded cross-over parallel study, Leucoselect® Phytosome® was administered for 4 weeks to 24 type-2 diabetic patients, significantly reducing urinary excretion of 8-epi-PGF in comparison with placebo. Enhanced urinary excretion of 8-epi-PGF is a marker of oxidative stress linked with increased formation of F2 isoprostanes, non enzymatic products of arachidonic acid peroxidation.
Diabetes is a chronic pathological state associated with enhanced lipid peroxidation, microvascular complication, development of atherosclerosis and thromboembolic events

Effect of Leucoselect® Phytosome® on urinary
excretion of 8-iso-PGF2α in diabetic patients

Pharmacology

The pharmacological profile of Leucoselect® Phytosome® has been defined by extensive in vitro and in vivo experimental studies. For the in vitro studies it has been used in the uncomplexed form.

In vitro(15-21)

In vivo


Percentage coverage of aortic arch by fatty lesions in mild experimental atherosclerosis in rabbits

 

Cardiovascular protective activity(22)

Leucoselect® Phytosome®, administered for 3 weeks at 2.4% concentration in a standard diet, reduced ischemia/reperfusion induced damages in the heart of young and aged rats. The recovery of myocardial function, expressed by left ventricular developed pressure (LVDP), at the end of reperfusion was 93% and 74% of the preischemic values, respectively. The protective effect on heart contractility was also strictly associated with a preserved coronary blood flow, expressed by the reduction of coronary perfusion pressure (CPP) close to the preischemic value both in young and aged rats.


Effect of Leucoselect® Phytosome® on left ventricular developed pressure and on coronary perfusion pressure in aged rats

Conclusive remarks

Leucoselect® Phytosome® was proven able to reduce oxidative stress and to improve plasma antioxidant defences both in physiological and pathological conditions. The efficacy of Leucoselect® Phytosome® is guaranteed by its fully elucidated chemical composition and its standardized content of smaller size OPCs. The patented Phytosome® formulation further enhances OPCs bioavailability.
Hence it represents an effective and safe aid in the prevention of chronic diseases of the cardiovascular system.

 

Please note that this web site is not aimed at consumers as the information herein contained does not make reference to finished products. Please note this website is accessible from various countries all over the world and hence it may contain statements or product classification not applicable to your country. The claims made are in reference to ingredients only, hence they do not refer to finished products and they may not comply with Regulation 1924/2006/CE. The marketer of any finished product containing any ingredient is responsible for assuring that the destination of the product and the claims made for the finished product are lawful and comply with all applicable laws and regulations of the country or countries in which the product is to be sold.

 

1. Shi J., Yu J., Pohorly E.J., Kakuda Y., J. Med. Food 6, 291 (2003).
2. Ursini F, Sevanian A., Wine polyphenols and optimal nutrition, Ann N Y Acad Sci. 2002 May;957:200-9.
3. Frankel E.N., Kanner J., German J.B., Parks E., Kinsella J.E., Lancet 341, 454 (1993).
4. Maxwell S., Cruickshank A., Thorpe G., Lancet 344, 193 (1994).
5. Bombardelli E., Morazzoni P., Fitoterapia 66, 291 (1995).
6. Morazzoni P., Magistretti M.J., Giachetti C., Zanolo G., Eur. J. Drug Metabol. Pharmacokinet. 17, 39 (1992).
7. Conti M., Malandrino S., Magistretti M.J., Jpn J. Pharmacol. 60, 315 (1992).
8. Scalbert A., Williamson G., J. Nutr. 130, 2073S (2000).
9. Gabetta, B., et al., Characterization of proanthocyanidins from grape seeds. Fitoterapia, 2000. 71(2): p. 162-75.
10. Deprez S., Mila I., Huneau J.F., Tome D., Scalbert A., Antioxid Redox Signal. 3, 957 (2001).
11. Nuttal S.L., Kendall M.J., Bombardelli E., Morazzoni P., An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect, J. Clin. Pharm. Ther. 23, 385 (1998).
12. Natella, F., et al., Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans. J Agric Food Chem, 2002. 50(26): p. 7720-5.
13. Vigna G.B., Costantini F., Aldini G., Carini M., Catapano A., Schena F., Tangerini A., Zanca R., Bombardelli E., Morazzoni P., Mezzetti A., Fellin R., Maffei Facini R., Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers, Metabolism 52, 1250 (2003).
14. Indena S.p.A., data on file.
15. Maffei Facino R., Carini M., Aldini G., Bombardelli E., Morazzoni P., Morelli R., Free radicals scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action, Arzneim.-Forsch./Drug Res. 44, 592 (1994).
16. Maffei Facino R., Carini M., Aldini G., Berti F., Rossoni G., Bombardelli E., Morazzoni P., Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability, Planta Medica 62, 495 (1996).
17. Maffei Facino R., Carini M., Aldini G., Calloni M.T., Bombardelli E., Morazzoni P., Sparing effect of procyanidins from Vitis vinifera on vitamin E: in vitro studies., Planta Medica 64, 343 (1998).
18. Carini M., Stefani R., Aldini G., Ozioli M., Maffei Facino R., Procyanidins from Vitis vinifera seeds inhibit the respiratory burst of activated human neutrophils and lysosomal enzyme release, Planta Med. 2001 Nov;67(8):714-7.
19. Aldini G., Carini M., Bombardelli E., Maffei Facino R., Polyphenols Communications 2002, XXI International Conference on Polyphenols,
Marrakech, Morocco, September 9-12, 2002.
20. Berti F., Manfredi B., Mantegazza P., Rossoni G., , Procyanidins from Vitis vinifera seeds display cardioprotection in an experimental model of ischemia-reperfusion damage, Drugs Exp Clin Res. 2003;29(5-6):207-16.
21. Aldini G., Carini M., Piccoli A., Rossoni G., Maffei Facino R., Procyanidins from grape seeds protect endothelial cells from peroxynitrite damage and enhance endothelium-dependent relaxation in human artery: new evidences for cardio-protection., Life Sciences 73, 2883 (2003).
22. Facino RM, Carini M, Aldini G, Berti F, Rossoni G, Bombardelli E, Morazzoni P., Diet enriched with procyanidins enhances antioxidant activity and reduces myocardial post-ischaemic damage in rats, Life Sci. 1999;64(8):627-42.
23. Ursini F, Tubaro F, Rong J, Sevanian A., Optimization of nutrition: polyphenols and vascular protection, Nutr Rev. 1999 Aug;57(8):241-9.
24. Study performed at the University of Milan, Institute of Pharmacological Sciences, School of Pharmacy, Prof. C. Galli. (Indena S.p.A., data on file).

 

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