Antioxidant activity |
Inhibition of cyclic nucleotide
phosphodiesterases |
Antiplatelet
activity |
Interaction with collagen, phospholipids and
proteoglycans |
Effect on arteriolar
vasomotion |
Chemoprevention
|
Cohort studies
The most characteristic compounds present in bilberry fruits are colorful
polyphenols belonging to the classes of anthocyanins-
and of proanthocyanidins.
The pharmacological properties of these substances seem nowadays well
ascertained; they are mainly linked to a strong antioxidant capacity, although
associated with many other biological activities, such as anti-inflammatory,
vasoactive, hypolipemic, hypoglycemic, cell-regenerating, antimicrobial,
chemopreventive, etc. Almost all of these properties have been intensively
studied, both in vitro and in vivo.
Antioxidant activity:
Bilberry anthocyanins and some related aglycones are reported to be potent
scavengers of free radicals, as when tested in vitro in the superoxide anion
generating system hypoxanthine/xanthine oxidase.
(1,2)
Anthocyanin extracts of
Vaccinium myrtillus fruits have been shown to
act both as scavengers against superoxide anion and as inhibitors of lipid
peroxidation in rat liver microsomes.
(3-5)
Cyanidin and delphinidin chlorides proved to be potent scavengers, interacting
with 1,1-diphenyl-1-picrylhydrazyl (DPPH) free radical: the IC50 values were
2.5 and 4.0 µM, respectively, comparable to that of quercetin.
Cyanidin chloride is the most active compound on CCl4 induced lipoperoxidation.
(6)
Laplaud
et al.(7) reported that an
aqueous extract of
V. myrtillus berries protected low-density
lipoproteins (LDL) from copper-mediated oxidation.
As reported by Rasetti
et al.(8) a
proprietary Bilberry extract was capable of protecting apolipoprotein B from
UV-induced oxidative fragmentation.
Ichiyanagi
et al.(9) studied the
activity of 11 major bilberry anthocyanins against hydroxyl radicals (OH°),
superoxide anion, and singlet oxigen by using capillary zone electrophoresis.
The reactivity of anthocyanins towards OH° was comparable to that of (+)-catechin
used as reference substance, and was neither significantly affected by the
aglycon structure nor by the conjugated sugar type. On the contrary, the
reactivity towards superoxide anion and singlet oxygen were determined by the
aglycon structure.
K. Nakanishi
et al.
(10) have
demonstrated that anthocyanins-rich bilberry extracts can prevent the
light-induced photo-oxidation of A2E, the major eye lipofuscin. Lipofuscins, a
class of orange and fluorescent pigments, accumulate with age in retinal epithelium, and are therefore also known as "age pigments". They have
been suggested to play a critical role in the pathogenesis of age-related
macular degeneration (AMD), the major cause of blindness in industrialized
countries. When exposed to light, lipofuscins generate singlet oxygen, a
reactive oxygen species that trigger degeneration of the visual epithelium.
This process was suppressed by bilberry anthocyanins, and protection from
retinal photo-oxydation might be an important mechanism for the eye beneficial
effects of bilberry anthocyanins.
In a more recent study on gene expression determined by microarray analysis,
it was shown that Mirtoselect
® anthocyanins can
attenuate the expression level of pro-inflammatory genes and restore that of
anti-inflammatory genes in an inflammatory cell model, providing a
rationale for the anti-inflammatory activity of bilberry anthocyanosides
(11).
A catechol moiety on ring B was found critical for the anti-inflammatory
activity of anthocyanins
(12). Remarkably,
80% of the anthocyanins of Mirtoselect
® belong to this
structural type.
Prior
et al.(13) comparing the
antioxidant capacity (oxygen radical absorbance capacity, ORAC) of different
variety of four Vaccinium species found that
V. myrtillus and
V.
angustifolium (low bush) exhibited potent ORAC activity (44.6±2.3 and
45.9±2.2, respectively).
A linear relationship existed between ORAC and anthocyanins (rxy = 0.77) or
total phenolic content (rxy = 0.92).
Anthocyanins can also prevent the oxidation of ascorbic acid caused by metal
ions by chelating the metals ions and forming an ascorbic acid (copigment)-metal-anthocyanin
complex.
(14) In addition the anthocyanins
extract is reported to inhibit the K+ loss induced by free radicals in human
erythrocytes as well as the cellular reactions induced by the oxidative
compounds daunomycin and paraquat.
(15,16).
Most recent studies
(17) indicate that
Mirtoselect
® is active in protecting the kidneys form damage
induced by potassium bromate in mice. Potassium bromate is an environmental
pollutant, which can be formed as a by-product in the process of ozone
purification of drinking water. It may form free radicals triggering harmful
modifications in the kidney tissue.
The protective properties of bilberry extract are due to the improved
antioxidant capacity of the kidney tissue promoted by bilberry anthicyanins:
the reduction of NO production and the improved ability to absorb oxygen
radical (ORAC).
Li Bao
et al.(18) showed that
Mirtoselect
® is able to alleviate stress-induced liver damage in
mice by both scavenging free radicals activity and lipid peroxidation
inhibitor effect. In a following study
(19)
the same group showed that
Mirtoselect
® restored alanine aminotransferase (ALT) and reactive
oxygen species (ROS) to normal levels, and enhanced mitochondrial complex II
activity that was lowered in the experimental conditions.
In a recent study in mice Endotoxin-induced uveitis (EIU)
(20),
Mirtoselect
®, has been shown to reduce levels of nitric oxide and malondialdehyde in eyes and to elevate ORAC,
glutathione,
vitamin C, superoxide dismutase, glutathione peroxidase activity in eyes. Moreover, Mirtoselect
® increased
expression of copper/zinc superoxide dismutase, manganese superoxide
dismutase, and glutathione peroxidase mRNA, indicating that Mirtoselect
® could attenuate
inflammation-induced oxidative
stress in EIU by increasing levels of antioxidants.
1. Salvayre R., Braquet P., Perruchot Th., Douste-Blazy L., in « Flavonoids
and Bioflavonoids, 1981 », L. Farkas, M. Gábor, F. Kállay, H. Wagner (Eds),
Elsevier, Amsterdam, 1982, pp 437-442.
2. Acquaviva R., Russo
A., Galvano F., Galvano G., Barcellona M.L., Li Volti G., Vanella A., "Cyanidin
and cyanidin 3-O-beta-D -glucoside as DNA cleavage protectors and
antioxidants", Cell. Biol. Toxicol. 19, 243 (2003).
3. Meunier M.T., Duroux E., Bastide P., Plant médicin. Phytothér. 23, 267
(1989).
4. Martín-Aragón S., Basabe B., Benedí J.M., Villar A.M., Phytother. Res.
12 Suppl.1, Second International Symposium on Natural Drugs, 1997, S104-S106
(1998).
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(1988).
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A., Chapman M.J., "Antioxidant action of Vaccinium myrtillus extract on
human low density lipoproteins in vitro: initial observations.", Fundam.
Clin. Pharmacol. 11, 35 (1997).
8. Rasetti M.F., Caruso D., Galli G., Bosisio E., Phytomedicine 3, 335
(1996/97).
9. Ichiyanagi T., Hatano Y., Matsugo S., Konishi T.,
"Kinetic comparisons of anthocyanin reactivities towards
2,2'-azobis(2-amidinopropane) (AAPH) radicals, hydrogen peroxide and
tert-buthylhydroperoxide by capillary zone electrophoresis", Chem Pharm
Bull (Tokyo). 2004 Apr;52(4):434-8.
10. Sparrow JR,
Vollmer-Snarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, Nakanishi K.
A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and
other antioxidants inhibit A2E-epoxide formation. J. Biol. Chem., Vol. 278,
Issue 20, 18207-18213 (2003).
11. Chen, Jihua, Uto,
Takuhiro, Tanigawa, Shunsuke, Kumamoto, Takuma, Fujii, Makoto and Hou,
De-Xing. "Expression Profiling of Genes Targeted by Bilberry (Vaccinium
myrtillus) in Macrophages Through DNA Microarray", Nutrition and Cancer,
60:1,43 - 50 (2008).
12. Hou DX,
Yanagita Y, Uto T, Masuzaki S, and Fujii, M. "Anthocyanidins inhibit
cyclooxygenase-2 expression in LPS-evoked macrophages:
structure-activity relationship and molecular mechanisms involved. Biochem
Pharmacol 70, 417–425, 2005.
13. Prior R.L., Cao G., Martin A., Sofic E., McEwen J., O’Brien C., Lischner
N., Elhenfeldt M, Kalt W., Krewer G., Mainland C.M., J. Agric. Food Chem. 46,
2686 (1998).
14. Sarma A.D., Sreelakshmi Y., Sharma R., Phytochemistry 45, 671 (1997).
15. Maridonneau I., Braquet P., Garay R.P. in "Flavonoids and
Bioflavonoids, 1981", L. Farkas, M. Gábor, F. Kállay, H. Wagner (Eds),
Elsevier, Amsterdam, 1982, pp 427-436.
16. Mavelli I., Rossi L., Autuori F., Braquet P., Rotilio G., in "Oxy
Radicals Their Scavenger Syst.", Proc. Int. Conf. Superoxide Dismutase,
3dr 1982 , G. Cohen , R.A. Greenwald , Elsevier, New York, 1983, pp 326-329.
17. Bao L., Yao XS., Tsi
D., Yau CC., Chia CS., Nagai H., Kurihara H., "Protective effects of
bilberry (Vaccinium myrtillus L.) extract on KBrO3-induced kidney damage in
mice", J. Agric. Food Chem., 56, pag. 420-425 (2008)
18. Li Bao, Xin-Sheng
Yao, Chin-Chin Yau, Daniel Tsi, Chew-Sern Chia, Hajme Nagai, Hiroshi Kurihara,
"Protective effects of bilberry (Vaccinium myrtillus L.) extract on
restraint stress-induced liver damage in mice" J. Agric. Food Chem.,
Published on Wed August 9, 2008.
19. Bao L, Abe K, Tsang P, Xu
JK, Yao XS, Liu HW, Kurihara H. Bilberry extract protect restraint stress-induced liver damage through attenuating mitochondrial dysfunction,
Fitoterapia. Volume 81, Issue 8, December 2010, Pages 1094-1101
20. Yao N. Protective effects of bilberry
(Vaccinium myrtillus L.) extract against Endotoxin-induced uveitis in mice. J.
Agric. Food Chem., 2010, 58
(8), pp 4731–4736
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