Non-pharma therapy for glaucoma and other
al. 1996; Ahlemeyer & Krieglstein 2003) GBE
(Consensus document 2010)
protects against glutamate toxicity.
(Chandrasekaran et al. 2002; Chandrasekaran et
Ginkgo biloba extract (GBE)
al. 2003) It can reduce glutamate-inducedelevation of calcium concentrations (Zhu et al.
Ginkgo biloba extract contains over 60 known
1997) and can reduce oxidative metabolism in
bioactive compounds, about 30 of which are
both resting and calcium-loaded neurons. (Oyama
found nowhere else in nature. The standardized
et al. 1994) Neurons in tissue culture are protected
extract used most widely in clinical research,
from a variety of toxic insults by GBE, which
EGb 761 (Dr Willmar Schwabe GmbH & Co,
inhibits apoptosis. (Ahlemeyer et al. 1999; Zhou &
Zhu 2000; Guidetti et al. 2001; Lu et al. 2006)
flavone glycosides (flavonoids), 6% terpenelactones (ginkgolides and bilobalide),
GBE improves both peripheral and cerebral blood
flow. It is effective in treating Raynaud’s disease,
other, uncharacterized compounds. (De Feudis
which is strongly associated with normal-tension
glaucoma. (Muir et al. 2002; Choi et al. 2009) Ithas been reported to protect myocardium against
GBE has been claimed effective in a variety of
hypoxia and ischemia-reperfusion injury (Haramaki
disorders associated with aging, including
et al. 1994; Punkt et al. 1995) and to relax blood
cerebrovascular disease, peripheral vascular
vessel walls. (Satoh & Nishida 2004) GBE is a
disease, dementia, tinnitus, bronchoconstriction,
strong inhibitor of platelet activating factor. (Koch
and sexual dysfunction. GBE appears to have
2005) There is mixed evidence for functional
many properties applicable to the treatment of
improvement in patients with Alzheimer’s-type and
non-IOP-dependent risk factors for glaucomatous
multi-infarct dementias. Preliminary data suggest
damage. (Ritch 2000) GBE exerts significant
that GBE may increase the probability of survival
protective effects against free radical damage
in the elderly population. (Dartigues et al. 2007)
and lipid peroxidation in various tissues andexperimental systems. Its antioxidant potential is
It has been suggested that alterations in systemic
comparable to water soluble antioxidants such as
NO and ET-1 activity (endothelial dysfunction) are
ascorbic acid and glutathione and lipid soluble
involved in vascular dysregulation in glaucoma.
ones such as alpha-tocopherol and retinol
(Nicolela et al. 2003; Grieshaber & Flammer 2005;
acetate. (Köse & Dogan 1995) The antioxidant
Henry et al. 2006; Su et al. 2006) Ginkgo biloba
properties of are due to its direct free radical
extract reportedly attenuates endothelial
scavenging activity. Proteasome inhibitory
dysfunction (Zhou et al. 2006) and improvement of
properties of anthocyanins may contribute to their
peripheral circulation by GBE is at least partly
attributable to its effects on the NO-pathway or
neuroprotective activities, rationalizing their use
endothelium-dependent vasodilation. (Chen et al.
in neurodegenerative disorders. (Dreiseitel et al.
1997; Wu & Zhu 1999) Further studies of GBE on
the ocular circulation and progression of normal-tension glaucoma are warranted.
GBE preserves mitochondrial metabolism andATP production in various tissues and partially
In the eye, GBE may have a protective effect
prevents morphologic changes and indices of
against the progression of diabetic retinopathy
oxidative damage associated with mitochondrial
(Droy-Lefaix et al. 1996) and reduces ischemia-
aging. (Pierre et al. 1999; Janssens et al. 2000;
reperfusion injury in rat retina. (Szabo et al. 1993)
Sastre et al. 2002; Eckert et al. 2003; Eckert et
GBE protects retinal photoreceptors against light-
al. 2005) In contrast to other antioxidants, gingko
induced damage by preventing oxidative stress in
has the capacity to enter the inner mitochondrial
the retina. (Ranchon et al. 1999; Xie et al. 2007)
antioxidant at the mitochondrial level. (Hirooka et
prevented by simultaneous treatment with GBE.
al. 2004) It can scavenge nitric oxide (Marcocci
(Meyniel et al. 1992) In a rat model of central
et al. 1994) and possibly inhibit its production.
retinal artery occlusion, GBE reduced edema and
necrosis and blocked the reduction in b-waveamplitude. (Droy-Lefaix et al. 1993)
Substantial experimental evidence exists tosupport the view that GBE has neuroprotective
dexamethasone-induced IOP elevation in rabbits.
hypoxia/ischemia, seizure activity, cerebral
(Jia et al. 2008) It reduced the dexamethasone-
edema, and peripheral nerve damage. (Smith et
associated accumulation of extracellular materials
within the cribriform layers of the trabecular
(EGb 761) in global brain ischemia and in
excitotoxicity-induced neuronal death.
cellularity. In cultured human trabecular cells,
Pharmacopsychiatry 36 Suppl 1: S89-94.
GBE substantially reduced dexamethasone-induced myocilin expression. (Jia et al. 2008) Ma
Chen X, S Salwinski & TJF Lee (1997): Extracts
et al investigated the dosage dependence of
of Ginkgo biloba and ginsenosides exert cerebral
intragastral GBE versus saline on RGC survival
vasorelaxation via a nitric oxide pathway. Clin Exp
in the rat optic nerve crush model. The mean
survival rate increased significantly (P<0.001)from 58.4±9.0% in the saline group to 74.2±6.8%
Choi WS, CJ Choi, KS Kim & et al (2009): To
in the high-dosage GBE group. The same group
compare the efficacy and safety of nifedipine
found that intraperitoneal administration gave
sustained release with Ginkgo biloba extract to
treat patients with primary Raynaud's phenomenonin South Korea; Korean Raynaud study (KOARA
GBE has been reported to improve automated
visual field indices. (Raabe et al. 1991; Quarantaet al. 2003) In one clinical cross-over study of
Chung HS, A Harris, JK Kristinsson, T Ciulla, C
Kagemann & R Ritch (1999): Ginkgo biloba
volunteers, GBE increased ophthalmic artery
extract increases ocular blood flow velocity. J
blood flow by a mean of 24%. (Chung et al.
Ocular Pharmacol Therap 15: 233-240.
1999) A more recent study, however, failed toconfirm these results. (Wimpissinger et al. 2007)
Dartigues JF, L Carcaillon, C Helmer & et al(2007): Vasodilators and nootropics as predictors
A systematic review of case reports concluded
of dementia and mortality in the PAQUID cohort. J
that the causality between ginkgo intake and
bleeding is unlikely’’. (Ernst et al. 2005) Asystematic review of eight randomized controlled
De Feudis FV (1991): Ginkgo biloba Extract (EGb
trials concluded that the available evidence does
761): Pharmacological activities and clinical
not demonstrate that GBE causes significant
applications. Paris. Elsevier: Pages.
changes in blood coagulation parameters’’.
(Savovic´ et al. 2005) The idea that the
Dreiseitel A, P Schreier, A Oehme & et al (2008):
combination of ginkgo and anticoagulant or
Inhibition of proteasome activity by anthocyanins
antiplatelet drugs might represent a serious
and anthocyanidins. Biochem Biophys Res Comm
health risk is based on several case reports but
not supported by clinical trials. (Izzo & Ernst2009)
Droy-Lefaix MT, ME Szabo & MN Doly (1993):Ischaemia and reperfusion-induced injury in the
spontaneously hypertensive rats: effects of free
therapeutic use of Ginkgo biloba extract for
radical scavengers. Int J Tissue React 15: 85-91.
Alzheimer's disease. Pharmacopsychiatry 36Suppl 1: S8-14.
Droy-Lefaix MT, ME Szabo-Tosaki & MN Doly(1996): Free radical scavenger properties of EGb
Ahlemeyer B, A Mowes & J Krieglstein (1999):
experimental diabetic retinopathy. In: RG Cutler, L
staurosporine-induced neuronal apoptosis by
Packe, J Bertram and A Mori (eds.) Book Title|.
constituents. Eur J Pharmacol 367: 423-430.
Eckert A, U Keil, S Kressmann & et al (2003):
Chandrasekaran K, Z Mehrabian, B Spinnewyn &
Effects of EGb 761 Ginkgo biloba extract on
et al (2002): Bilobalide, a component of the
mitochondrial function and oxidative stress.
Ginkgo biloba extract (EGb 761), protects
Pharmacopsychiatry 36 Suppl 1: S15-23.
against neuronal death in global brain ischemiaand in glutamate-induced excitotoxicity. Cell Mol
Eckert A, U Keil, I Scherping & et al (2005):
Stabilization of mitochondrial membrane potentialand improvement of neuronal energy metabolism
Chandrasekaran K, Z Mehrabian, B Spinnewyn &
by Ginkgo biloba extract EGb 761. Ann NY Acad.
bilobalide, a component of Ginkgo biloba extract
Ernst E, PH Canter & JT Coon (2005): Does
of Ginkgo biloba extracts. Phytomedicine 12: 10-
Ginkgo biloba increase the risk of bleeding’ A
systemic review of case reports. Perfusion 18:52-6.
Köse K & P Dogan (1995): Lipoperoxidationinduced by hydrogen peroxide in human
Grieshaber MC & J Flammer (2005): Blood flow
erythrocyte membranes. 2. Comparison of the
in glaucoma. Curr Opin Ophthalmol 16: 79-83.
antioxidant effect of Ginkgo biloba extract (EGb761) with those of water-soluble and lipid-soluble
Guidetti C, S Paracchini, S Lucchini & et al
antioxidants. J Int Med Res 23: 9-18.
(2001): Prevention of neuronal cell damageinduced by oxidative stress in vitro: effect of
Lu G, Y Wu, YT Mak & et al (2006): Molecular
different Ginkgo biloba extracts. J Pharmacy
evidence of the neuroprotective effect of Ginkgo
biloba (EGb761) using bax/bcl-2 ratio after brainischemia in senescence-accelerated mice, strain-
Haramaki N, S Aggarwal, T Kawabata, MT Droy-
Lefaix & L Packer (1994): Effects of naturalantioxidant Ginkgo biloba extract (EGb 761). On
Ma K, L Xu, H Zha & et al (2009): Dosage
myocardial ischemia-reperfusion injury. Free
dependence of the effect of Ginkgo biloba on the
rat retinal ganglion cell survival after optic nervecrush. Eye 23: 1598-1604.
Henry E, DE Newby, DJ Webb, PW Hadoke & CJO'Brien (2006): Altered endothelin-1
Ma K, L Xu, H Zhang & et al (2009): The effect of
vasoreactivity in patients with untreated normal-
ginkgo biloba on the rat retinal ganglion cell
pressure glaucoma. Invest Ophthalmol Vis Sci
survival in the optic nerve crush model. Acta
Hirooka K, M Tokuda, O Miyamoto & et al
Marcocci L, JJ Maguire, MT Droy-Lefaix & L
(2004): The Ginkgo biloba extract (EGb 761)
Packer (1994): The nitric oxide-scavenging
provides neuroprotective effect on retinal
properties of Ginkgo biloba extract (EGb 761).
ganglion cells in a rat model of chronic glaucoma.
Biochem Biophys Res Commun 201: 748-755.
Meyniel G, M Doly, M Millerin & P Braquet (1992):
Izzo AA & E Ernst (2009): Interaction between
Involvement of PAF (Platelet-Activating Factor) in
herbal medicines and prescribed drugs. An
chloroquine-induced retinopathy. C R Acad Sci III
updated systematic review. Drugs 69: 1777-
Muir AH, R Robb, M McLaren, F Daly & JJ Belch
Janssens D, E Delaive, J Remacle & C Michiels
(2002): The use of Ginkgo biloba in Raynaud's
(2000): Protection by bilobalide of the ischaemia-
disease: a double-blind placebo-controlled trial.
respiratory activity. Fundam Clin Pharmacol 14:193-201.
Nicolela MT, SN Ferrier, CA Morrison & et al(2003): Effects of cold-induced vasospasm in
Jia LY, L Sun, DS Fan & et al (2008): Effect of
glaucoma: the role of endothelin-1. Invest
topical Ginkgo biloba extract on steroid-induced
changes in the trabecular meshwork andintraocular pressure. Arch Ophthalmol 126: 1700-
Oyama Y, PA Fuchs, N Katayama & K Noda
(1994): Myricetin and quercetin, the flavonoidconstituents of Ginkgo biloba extract, greatly
Kobuchi H, MT Droy-Lefaix, Y Christen & L
reduce oxidative metabolism in both resting and
Packer (1997): Ginkgo biloba extract (EGb
Ca (2+)-loaded brain neurons. Brain Res 635:125-
761): Inhibitory effect on nitric oxide production in
the macrophage cell line RAW 264.7. BiochemPharmacol 53: 897-904.
Pierre S, I Jamme, MT Droy-Lefaix & et al (1999):Ginkgo biloba extract (EGb 761) protects NaK-
Koch E (2005): Inhibition of platelet activating
ATPase activity during cerebral ischemia in mice.
factor (PAF)-induced aggregation of human
thrombocytes by ginkgolides: considerations onpossible bleeding complications after oral intake
Punkt K, K Welt & L Schaffranietz (1995):
induced ion shifts (Na+, K+, Ca2+ and Mg2+ by
free radical scavengers in the rat retina.
myocardium caused by experimental hypoxia
with and without ginkgo biloba extract EGb 761pretreatment. A cytophotometrical study. Acta
Wimpissinger B, F Berisha, G Garhoefer & et al
(2007): Influence of Gingko biloba on ocular bloodflow. Acta Ophthalmol Scand 85: 445-9.
Quaranta L, S Bettelli, MG Uva & et al (2003):Effect of Ginkgo biloba extract on pre-existing
Wu WR & XZ Zhu (1999): Involvement of
visual field damage in normal tension glaucoma.
monoamine oxidase inhibition in neuroprotective
and neurorestorative effects of Ginkgo bilobaextract against MPTP-induced nigrostriatal
Raabe A, M Raabe & P Ihm (1991): Therapeutic
dopaminergic toxicity in C57 mice. Life Sci 65:
follow-up using automatic perimetry in chronic
cerebroretinal ischemia in elderly patients.
Prospective double-blind study with graduated
dose Ginkgo biloba treatment. Klin Monatsbl
Intraperitoneal injection of Ginkgo biloba extract
enhances antioxidation ability of retina andprotects photoreceptors after light-induced retinal
Ranchon I, JM Gorrand, J Cluzel, MT Droy-Lefaix
damage in rats. Curr Eye Res 32: 471-9.
& M Doly (1999): Functional protection ofphotoreceptors from light-induced damage by
Zhou LJ & XZ Zhu (2000): Reactive oxygen
dimethylthiourea and Ginkgo biloba extract.
species-induced apoptosis in PC12 cells and
Invest Ophthalmol Vis Sci 40: 1191-1199.
protective effect of bilobalide. J Pharmacol ExpTher 293: 982-988.
Ritch R (2000): A potential role for Ginkgo bilobaextract in the treatment of glaucoma. Medical
Zhou W, H Chai, A Courson & et al (2006):
Ginkgolide A attenuates homocysteine-inducedendothelial dysfunction in porcine coronary
Sastre J, A Lloret, C Borras & et al (2002): GBE
EGb 761 protects against mitochondrial aging inthe brain and in the liver. Cell Mol Biol 48: 685-
Zhu L, J Wu, H Liao, J Gao, XN Zhao & ZX Zhang
(1997): Antagonistic effects of extract from leavesof Ginkgo biloba on glutamate neurotoxicity. Acta
Electropharmacological actions of Ginkgo bilobaextract on vascular smooth and heart muscles.
Grape seed extract
Grape seed proanthocyanidins have a broad
Savovic´ J, B Wider & E Ernst (2005): Effects of
spectrum of pharmacological and medicinal
Ginkgo biloba on blood coagulation parameters:
properties against oxidative stress. Grape seed
a systematic review of randomised clinical trials.
proanthocyanidin extract (GSE) provides excellent
Evid Based Integrative Med 2: 167-76.
protection against free radicals in both in vitro andin vivo models. (Bagchi et al. 2002) GSE-induced
Smith PF, K Maclennan & CL Darlington (1996):
improvement in myocardial ischemia-reperfusion
The neuroprotective properties of the Ginkgo
injury in vitro has been reported. (Pataki et al.
biloba leaf: a review of the possible relationshiop
2002; Bagchi et al. 2003; Shao et al. 2003) Activin,
a new generation antioxidant derived from grape
seed proanthocyanidins, reduces plasma levels ofoxidative stress and adhesion molecules (ICAM-1,
Su WW, ST Cheng, TS Hsu & WJ Ho (2006):
VCAM-1 and E-selectin) in patients with systemic
Abnormal flow-mediated vasodilation in normal-
sclerosis. (Kalin et al. 2002) Supplementation of a
meal with GSE minimizes postprandial oxidative
stress by increasing the antioxidant levels in
dysfunction. Invest Ophthalmol Vis Sci 47: 3390-
plasma, and, as a consequence, enhancing the
resistance to oxidative modification of low densitylipoproteins. (Natella et al. 2002) Grape seed
Szabo ME, MT Droy-Lefaix, M Doly & P Braquet
proanthocyanidins have also been reported to
(1993): Modification of ischemia/reperfusion-
have activity against HIV-1 entry into cells. (Nair et
al. 2002) Grape seed extract has recently been
Shigematsu et al. 2003) It inhibits lipid
shown to inhibit the growth of prostate cancer
peroxidation of low-density lipoprotein (LDL),
cells in mice. (Raina et al. 2007) In the eye, GSE
prevents the cytotoxicity ofoxidized LDL, and
inhibits key components of cataractogenesis by
protects cells against lipid peroxidation.
reducing oxidative stress within lens epithelial
(Chanvitayapongs et al. 1997) Resveratrol
cells. (Barden et al. 2008) and significantly
protects against the degeneration of neurons
prevents and postpones development of cataract
afteraxotomy. (Araki et al. 2004) A single infusion
formation in rats with hereditary cataracts.
of resveratrol can elicit neuroprotective effects on
cerebral ischemia-induced neuron damagethrough free radical scavenging and cerebral blood
elevation due to nitric oxide release. (Lu et al.
2006) Its antiapoptotic activity has led to the
Resveratrol (3,5,40-trihydroxystilbene), a
suggestion that resveratrol may make a useful
powerful polyphenolic antioxidant, is found
dietary supplement for minimizing oxidative injury
largely in the skins of red grapes and berries and
in immune-perturbed states and human chronic
came to scientific attention as a possible
explanation for the low incidence of heart diseaseamong the French, who eat a relatively high-fat
Levels of intracellular heme (iron-protoporphyrin
diet (the French paradox). Many studies suggest
IX), a pro-oxidant, increase after stroke. In
that consuming alcohol (especially red wine)
neuronal cell cultures, resveratrol induces heme
may reduce the incidence of coronary heart
oxygenase 1, suggesting that increased heme
disease (CHD). Grape juice, which is not a
oxygenase activity is a unique pathway by which
fermented beverage, is not a significant source of
resveratrol can exert its neuroprotective actions.
resveratrol. A large number of studies in the past
few years suggests its benefit in vitro and in vivoin a variety of human disease models, including
Resveratrol directly inhibits CYP1B1. The
cardioprotection, neuroprotection, immune
versatility of RSV lies in its diverse targeting of
regulation, and cancer chemoprevention. For an
membrane and intracellular receptors, signaling
extensive review, see (Pervaiz & Holme 2009).
Substantial data show that actions of resveratrol
include inhibition of lipid peroxidation and platelet
transcription factors, and it can activate or repress
aggregation, metal chelating (primarilycopper),
a number of signal-transducing pathways found
free radical’scavenging activity, antiinflammatory
throughout the cell (Pervaiz & Holme 2009)
activity, modulation of lipid metabolism,antifungal properties, and anticancer and
There appears to be an association between aging
estrogen-like activity. (Pervaiz & Holme 2009)
and neurodegenerative diseases, such asAlzheimer’s, and that modulation by both caloric
Resveratrol increases the lifespan of the yeast,
restriction and drugs which mimic caloric
restriction, such as resveratrol, can ameliorate
Caenorhabditis elegans, and the fruitfly,
these diseases. (Liu et al. 2007) Resveratrol
Drosophila melanogaster. It was later shown to
reduces the levels of secreted and intracellular
extend the lifespan of the short-lived fish,
amyloid-ß peptides by proteosomal degradation.
Nothobranchius furzeri, (Valenzano & Cellerino
2006) and has now been shown to significantlyincrease the health and survival of mice on a
In the eye, resveratrol suppresses selenite-
high-calorie diet, pointing to a new approach to
induced oxidative stress and cataract formation in
treating diseases of aging. (Baur et al. 2006)
rats. (Doganay et al. 2006) The authors suggested
Among its multiple functions, resveratrol
that the presence of oxidative stress in selenite
activates sirtuins (silent information regulator
cataract development and its prevention by
proteins), a family of proteins that play an
resveratrol support the possibility that high natural
important role in DNA repair, gene silencing,
consumption of resveratrol in food can help
chromosomal stability and longevity. (Michan &
prevent human senile cataract. Resveratrol also
induces dilation of retinal arterioles, suggesting apotential benefit for this compound in the treatment
The physiologic effects of resveratrol appear to
of retinal vascular disease. (Nagaoka et al. 2007)
be related to its ability to regulate nutrition and
Sirtuin-1 activators (such as resveratrol)
longevity genes. (Pervaiz & Holme 2009)
demonstrate neuroprotective properties in mouse
Resveratrol is an effective antioxidant. (Frankel
models of optic neuritis and multiple sclerosis.
et al. 1993; Chanvitayapongs et al. 1997;
radical scavenging and cerebral blood flow
Araki T, Y Sasaki & J Milbrandt (2004):
elevation. J Agric Food Chem 54: 3126-31.
Increased nuclear NAD biosynthesis and SIRT1activation prevent axonal degeneration. Science
Marambaud P, H Zhao & P Davies (2005):
Resveratrol promotes clearance of Alzheimer’sdisease amyloid-beta peptides. J Biol Chem 280:
Bagchi D, M Bagchi, S Stohs & et al (2002):
Cellular protection with proanthocyanidinsderived from grape seeds. Ann N Y Acad Sci
Michan S & D Sinclair (2007): Sirtuins in
mammals: Insights into their biological function.
Biochem J 404: 1’13.
Bagchi D, CK Sen, SD Ray & et al (2003):Molecular mechanisms of cardioprotection by a
Nagaoka T, TW Hein, A Yoshida & et al (2007):
novel grape seed proanthocyanidin extract. Mutat
Resveratrol, a component of red wine, elicits
dilation of isolated porcine retinal arterioles: role ofnitric oxide and potassium channels. Invest
Barden CA, HL Chandler, P Lu & et al (2008):
Effect of grape polyphenols on oxidative stress incanine lens epithelial cells. Am J Vet Res 69: 94-
Nair MP, C Kandaswami, S Mahajan & et al
(2002): Grape seed extract proanthocyanidinsdownregulate HIV-1 entry coreceptors, CCR2b,
Baur JA, KJ Pearson, NL Price & et al (2006):
Resveratrol improves health and survival of mice
peripheral blood mononuclear cells. Biol Res 35:
on a high-calorie diet. Nature 444: 337-342.
Chanvitayapongs S, B Draczynska-Lusiak & AY
Natella F, F Belelli, V Gentili & et al (2002): Grape
Sun (1997): Amelioration of oxidative stress by
antioxidants and resveratrol in PC12 cells.
postprandial oxidative stress in humans. J Agric
Doganay S, M Borazan, M Iraz & Y Cigremis
Pataki T, I Bak, P Kovacs & et al (2002): Grape
(2006): The effect of resveratrol in experimental
cataract model formed by sodium selenite. Curr
recovery during reperfusion after ischemia in
isolated rat hearts. Am J Clin Nutrition 75: 894-899.
Frankel EN, AL Waterhouse & JE Kinsella(1993): Inhibition of human LDL oxidation by
Pervaiz S & AL Holme (2009): Resveratrol: Its
Biologic Targets and Functional Activity.
Antioxidants Redox Signaling 11: 2851-2897.
Kalin R, A Righi, A Del Rosso & et al (2002):Activin, a grape seed-derived proanthocyanidin
Raina K, RP Singh, R Agarwal & C Agarwal
extract, reduces plasma levels of oxidative stress
(2007): Oral grape seed extract inhibits prostate
and adhesion molecules (ICAM-1, VCAM-1 and
tumor growth and progression in TRAMP mice.
E-selectin) in systemic sclerosis. Free Radical
Shao ZH, LB Becker, TL Vanden Hoek & et al
Liu Q, F Xie, R Rolston & et al (2007):
(2003): Grape seed proanthocyanidin extract
Prevention and treatment of Alzheimer disease
attenuates oxidant injury in cardiomyocytes.
and aging: antioxidants. Mini Rev Med Chem 7:
Shigematsu S, S Ishida, M Hara & et al (2003):
Resveratrol, a red wine constituent polyphenol,
prevents superoxide-dependent inflammatory
mononuclear cells. Eur J Clin Invest 33: 818-823.
responses induced by ischemia/reperfusion,platelet-activating factor, or oxidants. Free Radic
Lu KT, RY Chiou, LG Chen & et al (2006):
Neuroprotective effects of resveratrol on cerebralischemia-induced neuron loss mediated by free
Shindler KS, E Verntura, TS Rex & et al (2007):SIRT1 activation confers neuroprotection in
experimental optic neuritis. Invest Ophthalmol Vis
attention deficit hyperactivity disorder in children.
Valenzano DR & A Cellerino (2006): Resveratrol
After oral administration of pycnogenol, plasma
and the pharmacology of aging: a new vertebrate
samples significantly inhibited NFkB activation and
model to validate an old molecule. Cell Cycle 5:
MMP-9 release from human monocytes, indicating
that it exerts anti-inflammatory effects by inhibitingproinflammatory gene expression. (Grimm et al.
Yamakoshi J, M Saito, S Kataoka & S Tokutake
2006) Glutamate inhibits cyclo-oxygenases 1 and
(2002): Procyanidin-rich extract from grape
2. (Schafer et al. 2006) This cytotoxicity was
seeds prevents cataract formation in hereditary
inhibited by both GBE and pycnogenol.
cataractous (ICR/f) rats. J Agric Food Chem 50:
(Kobayashi et al. 2000) Pycnogenol not only
suppresses the generation of reactive oxygenspecies, but also attenuates caspase-3 activation
Zhuang H, YS Kim, RC Koehler & S Dore
and DNA fragmentation, suggesting protection
against Aß-induced apoptosis. (Peng et al. 2002)
resveratrol, a red wine constituent, protectsneurons. Ann N Y Acad Sci 993: 276-286.
Pycnogenol has also been reported to inhibitangiotensin-converting enzyme and to enhance
the microcirculation by increasing capillarypermeability. (Packer et al. 1999) It inhibits
Pycnogenol, an extract of French maritime pine
progression of preproliferative diabetic retinopathy
bark (Pinus pinaster), is primarily composed of
(Schonlau & Rohdewald 2001) and may reduce
procyanidins and phenolic acids and is a potent
the risk of formation of both diabetic retinopathy
antioxidant with strong free radical-scavenging
and cataract. (Kamuren et al. 2006) More recently,
activity against reactive oxygen and nitrogen
in patients with mild to moderate retinal edema,
pycnogenol treatment significantly improved both
catechin and epicatechin subunits, which are
the edema and retinal thickness as measured by
important in human nutrition. (Rohdewald 2002)
high resolution ultrasound. (Steigerwalt et al.
2009) Laser Doppler flow velocity measurements
Pycnogenol is effective in patients with venous
at the central retinal artery showed a statistically
microangiopathy (Cesarone et al. 2006)and
significant increase from 34 to 44 cm/s in the
accelerates healing in leg ulcerations from
chronic venous insufficiency (Belcaro et al. 2005)
effects in the control group. (Steigerwalt et al.
and diabetes. (Belcaro et al. 2006) In chronic
venous insufficiency, pycnogenol reduced lowerleg circumference and symptoms of pain,
Steigerwalt et al (Steigerwalt et al. 2008)
evaluated the effects of the food supplement
‘heaviness", and reddening of the skin. (Koch
Mirtogenol (Mirtoselect and Pycnogenol) on IOP
and ocular blood flow in 20 subjects versus 18
endothelial cells from Aß-induced injury. (Liu et
controls. After three months of treatment, the IOP
was lowered compared to that of untreated
creatinine, BUN, LDH, IL-1beta, IL-6, and TNF-
controls from a baseline of 25.2 mmHg to 22.0
alpha levels in ischemia reperfusion injury in
mmHg (p<0.05). Ocular blood flow (central
unilaterally nephrectomized rats. (Ozer Sehirli et
retinal, ophthalmic, and posterior ciliary arteries)
improved both in the systolic and diastoliccomponents as measured by Color Doppler
Pretreatment with pycnogenol reduces smoke-
induced platelet aggregation. (Araghi-Niknam etal. 2000) Pycnogenol significantly reduces LDL-
cholesterol levels. (Devaraj et al. 2002; Koch
Rohdewald & RR Watson (2000): Pine bark
2002) A randomized controlled trial reported it
extract reduces platelet aggregation. Integrative
effective for erectile dysfunction. (Stanislavov et
al. 2007) It has also been reported to improvesymptoms of jetlag. (Belcaro et al. 2008) It
Belcaro G, MR Cesarone, BM Errichi & et al
inhibits not only HIV-1 binding to host cells, but
also its replication after entry in susceptible cells
improvement and faster healing with local use of
in vitro. (Feng et al. 2008) It has been reported to
increase urinary catecholamines and ameliorate
Belcaro G, MR Cesarone, BM Errichi & et al
Koch R (2002): Comparative study of Venostasin
(2006): Diabetic ulcers: microcirculatory
and Pycnogenol in chronic venous insufficiency.
improvement and faster healing with pycnogenol.
Liu F, BH Lau, Q Peng & V Shah (2000):
Belcaro G, MR Cesarone, RJ Steigerwalt & et al
Pycnogenol protects vascular endothelial cells
(2008): Jet-lag: prevention with Pycnogenol.
from beta-amyloid-induced injury. Biol Pharm Bull
Preliminary report: evaluation in healthy
individuals and in hypertensive patients. MinervaCardioangiol 56 (5 Suppl): 3-9.
Ozer Sehirli A, G Sener & F Ercan (2009):Protective effects of pycnogenol against ischemia
Cesarone MR, G Belcaro, P Rohdewald & et al
reperfusion-induced oxidative renal injury in rats.
(2006): Improvement of diabetic microangiopathy
with pycnogenol: A prospective, controlled study.
Angiology 57: 431-6.
Packer L, G Rimbach & F Virgili (1999):Antioxidant activity and biologic properties of a
Cesarone MR, G Belcaro, P Rohdewald & et al
procyanidin-rich extract from pine (Pinus
(2006): Rapid relief of signs/symptoms in chronic
maritima) bark, pycnogenol. Free Radic Biol Med
venous microangiopathy with pycnogenol: a
prospective, controlled study. Angiology 57: 569-76.
Peng QL, AR Buz'Zard & BH Lau (2002):Pycnogenol ( (R)) protects neurons from amyloid-
beta peptide-induced apoptosis. Brain Res Mol
Rohdewald & I Jialal (2002): Supplementation
with a pine bark extract rich in polyphenolsincreases plasma antioxidant capacity and alters
Rohdewald P (2002): A review of the French
the plasma lipoprotein profile. Lipids 37: 931-934.
maritime pine bark extract (Pycnogenol), a herbalmedication with a diverse clinical pharmacology.
Dvoráková M, D Jezová, P Blazícek & et al
Int J Clin Pharmacol Ther 40: 158-68.
(2007): Urinary catecholamines in children withattention deficit hyperactivity disorder (ADHD):
Schafer A, Z Chovanova, J Muchova & et a
modulation by a polyphenolic extract from pine
(2006): Inhibition of COX-1 and COX-2 activity by
bark (pycnogenol). Nutr Neurosci 10: 151-7.
plasma of human volunteers after ingestion ofFrench maritime pine bark extract (Pycnogenol).
Feng WY, R Tanaka, Y Inagaki & et al (2008):
Pycnogenol, a procyanidin-rich extract fromFrench maritime pine, inhibits intracellular
Schonlau F & P Rohdewald (2001): Pycnogenol
replication of HIV-1 as well as its binding to host
for diabetic retinopathy. A review. Int Ophthalmol
Grimm T, Z Chovanova, J Muchova & et al
Stanislavov R, V Nikolova & P Rohdewald (2007):
(2006): Inhibition of NF-kappaB activation and
Improvement of erectile function with Prelox: a
MMP-9 secretion by plasma of human volunteers
randomized, double-blind, placebo-controlled,
after ingestion of maritime pine bark extract
crossover trial. Int J Impot Res Aug 16; [Epub
(Pycnogenol). J Inflamm (Lond) 27: 1.
Kamuren ZT, CG McPeek, RA Sanders & JB
Steigerwalt R, G Belcaro, MR Cesarone & et al
(2009): Pycnogenol improves microcirculation,
carbohydrate diet and Pycnogenol treatment on
retinal edema, and visual acuity in early diabetic
retinal antioxidant enzymes in normal and
retinopathy. J Ocul Pharmacol Ther 25: 537-40.
diabetic rats. J Ocul Pharmacol Ther 22: 10-18.
Steigerwalt RD, B Gianni, M Paolo & et al (2008):
Kobayashi MS, D Han & L Packer (2000):
Effects of Mirtogenol on ocular blood flow and
Antioxidants and herbal extracts protect HT-4
intraocular hypertension in asymptomatic subjects.
cytotoxicity. Free Radic Res 32: 115-124.
Bankart Repair Post-Op Instructions Missouri Orthopaedic Institute Bankart Repair Post-Operative Instructions Seth L. Sherman, M.D. Tamara L Young, ATC, OTC, M.Ed Department of Sports Medicine Ø Anesthetic drugs used during surgery may cause nausea for the first 24 hours. If nausea is encountered, drink only clear liquids and light food (jello, soups, dry crackers, toast).
O Caminho neocatecumenal, iniciado por Kiko Argüello e Carmen Hernández em 1964 em Madrid, está presente em mais de 1.320 dioceses de 110 países nos 5 continentes, com 20.000 comunidades em aproximadamente 6.000 paróquias. Resumimos aqui o percurso institucional que se concluiu nestes dias com a aprovação doutrinal do “Diretório catequético do Caminho neocatecumenal”. • 1974 8