Subject: Re: pycnogenol

From: [email-masked] (Al Czap)
Date: 8 Aug 1995 19:15:34 GMT

In article <[email-masked]>, [email-masked] (Haoma) wrote:

> Could someone tell me where I could find some information online about 
> pycnogenol?
> 

Anthocyanosides, anthocyanins, and procyanidins are water-soluble
plant-derived flavonoids which have been widely studied for their
anti-inflammatory, antioxidant, and vascular actions.
   The oligomeric procyanidins (OPC's) are mixtures of water-soluble
oligomers, usually dimers and trimers of the cyanins (+)-catechin and
(-)-epicatechin.  They are found in many plants, including Cola acuminata
(cola), vaccinium vitis-idaea (cranberry), Vitis vinefera (grape), and the
bark of the maritime pine (Pinus pilaster or Pinus maritima).  The OPC's
have demonstrated capillary protective action through stabilization of
collagen, and possess significant antioxidant and anti-inflammatory
activity.  Incubation of collagen fibers with OPC's significantly
increased the number of crosslinks and delayed thermal denaturation. 
These effects were three to five times greater for OPC's than either
(+)-catechin or condensed tannin.  Binding of OPC's to elastin has also
been shown to inhibit its degradation by elastases during the inflammatory
process.  OPC's have demonstrated profound antioxidant activity against
both the DPPH radical and the superoxide ion in vitro, and were found to
be approximately 50 times more potent than vitamin E under the same
conditions.
   A clinical trial was carried out on 153 patients with various disorders
of the venous system (varicose veins, venous insufficiency, post-phlebitis
syndrome) of whom 78 were treated with OPC's and 75 with placebo.  The
results were evaluated on the basis of clinical criteria, both objectively
and subjectively.  Analysis of the results showed a statistically
significant difference between the treatment group and the placebo group. 
Several unpublished clinical studies commissioned by the Italian
pharmaceutical firm Damor have also been performed using OPC's, and show
significant positive effects in the treatment of veno-lymphatic
deficiency, varicose veins, and vascular disorders of the retina.

REFERENCES
   Natural Products as Medicinal Agents, Hippokrates Verlag, Stuttgart,
1980; pp 243-256
   Les Praticien 400:63, 1981
   Biochem Pharmacol 33:3933, 1984
   Med Sci Res 15:831, 1987
   University of Florence, Unpublished observations, 1989
   University of Aquila, Unpublished observations, 1989

ABSTRACTS

*"Endotelon" refers to a 95% oligomeric proanthocyanidin product extracted
>from  grape seeds.

Natural products as medicinal agents

During the winter of 1534, the French explorer Jaques Cartier and his crew
avoided scurvy by using Anneda, an Indian medicine probably containing
ascorbic acid and procyanidins.  Four centuries later, Szent-Gyorgyi was
misguided in proposing citrin [lemon flavonoid compound] as a second
antiscorbutic factor, for flavonoids are devoid of true vitamin-like
behavior.  On the other hand, pycnogenols, widely found in old empirical
antiscorbutic remedies, seem more appropriate in this respect, since they
are active per os, bioavailable, linked to various living tissues, and
concerned with essential metabolic pathways.  As histidine decarboxylase
inhibitors, pycnogenols lower the histamine level in the aortic
endothelium and are believed to protect it against the vascular
permeability alterations occurring early in the atherogenic process.

Masquelier J.  Natural products as medicinal agents.  Planta Med
242S-256S; 1980.

Flavonoids and pycnogenols

Pycnogenols is the term put forward by the authors to designate
flavan-3-ol derivatives, so as to distinguish these substances, upon
chemical and pharmacological grounds, from the heterogenous group of
flavonoid compounds.

Masquelier J, et al.  Flavonoids and pycnogenols.  Int J Vitam Nutr Res
49:307-311; 1979.

Double-blind study of Endotelon in chronic venous insufficiency

This article reports a double-blind study comparing procyanidolic
oligomers (Endotelon) with semi-synthetic diosmin in 50 patients with
symptoms of chronic venous insufficiency.  Both substances were effective
in peripheral venous insufficiency but there was a statistically
significant advantage in favor of procyanidolic oligomers (Endotelon) with
regard to rapidity and duration of action. 

Delacrois P.  Double-blind study of Endotelon in chronic venous
insufficiency.  La Revue De Med 27:28-31; 1981.

Effect of Endotelon in postoperative edema. Results of a double-blind
study with placebo on a group of thirty-two patients

This article reports on a double-blind test versus a placebo to assess the
prophylactic effect of these compounds on the formation of postoperative
edema following face-lifting.  The main criteria was the speed of
disappearance of the edemas after the operation.  A statistically
significant difference (p=0.01) was found in favour of the active
ingredient.  The mean figures were 11.4 days for the treated group and
15.8 days for the control group.

Baruch J.  Effect of Endotelon in postoperative edema. Results of a
double-blind study with placebo on a group of thirty-two patients.  Ann
Chir Plast Esthét 4; 1984.

Endotelon in the treatment of venolymphatic problems in premenstrual
syndrome, Multicenter study on 165 patients

The efficacy of Endotelon was judged on 165 patients undergoing ambulatory
treatment for various premenstrual problems.  Mammary symptoms, abdominal
swelling, pelvic pains, weight variations, and venous problems of the legs
disappeared or improved in 60.8% of the cases after 2 cycles of treatment
and in 78.8% of the cases after 4 cycles of treatment.  The beneficial
effect of Endotelon is prolonged and reinforced with the passage of time
and regards not only the intensity of the symptoms but also their
duration.  The effect of this product on the vasculatory constituents
offers an effective and well tolerated alternative to hormonal treatment
of premenstrual syndrome.

Amsellem M, et al.  Endotelon in the treatment of venolymphatic problems
in premenstrual syndrome, Multicenter study on 165 patients.  Tempo
Médical 282; 1987.

Light vision and chorioretinal circulation. Study of the effect of
procyanidolic oligomers (Endotelon)

Light vision is a major element of the visual function.  However, it
varies from one subject to another.  Many factors may modify it in the
absence of any retinal pathology (age, fatigue, stress).  A lower
resistance to glare and an alteration of scotopic vision are often
mentioned during medical visits.  We endeavored to obtain a protection
with Endotelon in subjects presenting no major retinal or ophthalmological
pathology.  Endotelon comes in tablets of 50 mg of procyanidolic
oligomers.  This compound of vegetal origin (from grape seeds) belongs to
the chemical class of flavones which selectively fix on collagen and
elastin fibers, thus reinforcing the structure of the vascular connective
tissue.  The drug efficiency on the resistance to glare and on the night
morphoscopic vision was demonstrated by means of three tests: Comberg's
nyctometer, Beyne's lantern, and ergovision.  One hundred subjects were
tested in two centers.  In both centers, a treated group received 4
tablets of Endotelon a day for five weeks and a control group received no
treatment.  Two patients stopped the experiment.  Nyctometer: the
improvement in the visual performances after glare as well as the rapidity
with which these results were obtained is very significant compared to the
results obtained in the control group.  Visual adaptation to low
luminances is also improved under treatment.  Ergovision tests were
performed in two light environments: a standard one and glare.  These
results support the previous ones.  There is a narrow correlation between
the decrease in visual performances after a quick retinal glare and the
increase in the environmental luminance at the time of inclusion.

Corbe C, Boissin JP, Siou A.  Light vision and chorioretinal circulation.
Study of the effect of procyanidolic oligomers (Endotelon). J Fr Ophtalmol
11:453-460; 1988.

A study of the effects of procyanidol oligomers on capillary resistance in
hypertension and in certain nephropathies

The effects of procyanidol oligomers on capillary resistance disorders in
hypertensive and diabetic patients were studied.  The preparation was
administered in a daily dose of 150 mg.  Concordant results were obtained
in two investigations as follows: during an open trial in 28 patients,
capillary resistance (measured by the technique of Lavollay) rose from
15.4 +/- 1.8 cm Hg to 18.1 +/- 3.2 cm Hg (p <0.0005); and during a
double-blind trial versus placebo (25 patients) capillary resistance rose
>from  14.6 +/- 0.98 cm Hg to 18 +/- 3.35 cm Hg (p <0.0005) in the treated
group, while no significant variation was observed in the placebo group
(15.5 +/- 1.30 cm Hg  versus 14.7 +/- 1.3 cm Hg initially).  The
preparation was well tolerated.

Lagrua G, Olivier-Martin F, Grillot A.  A study of the effects of
procyanidol oligomers on capillary resistance in hypertension and in
certain nephropathies. Sem Hop 57:1399-1401; 1981.

The effect of procyanidolic oligomers on vascular permeability. A study
using quantitative morphology

In normal conditions vascular permeability is precisely regulated by
mechanisms which involve among others macromolecules of the extracellular
matrix of the vascular wall.  Permeability for a given substance will vary
according to the anatomical localization of the vessel determining also
its structure and composition.  In some pathological conditions, such as
inflammation or diabetes, permeability can be abnormally increased. 
Increased permeability can be reproduced by i.v. collagenase injection. 
This permeability increase can be quantified by image analysis using
appropriate tracers, such as FITC-dextrans or horseradish peroxidase, on
histological sections from control and collagenase-treated rats,
pretreated or not with procyanidolic oligomers (PCO).  We studied cerebral
capillaries, aorta and cardiac muscle capillaries.  It could be shown that
previous treatment of animals with procyanidolic oligomers prevented the
permeability increase produced by collagenase injection.

Robert L, et al. The effect of procyanidolic oligomers on vascular
permeability. A study using quantitative morphology. Pathol Biol
38:608-616; 1990.

Evidence by in vivo and in vitro studies that binding of pycnogenols to
elastin affects its rate of degradation by elastases

Procyanidol oligomers and (+) catechin bound to insoluble elastin markedly
affect its rate of degradation by elastases.  Insoluble elastin pretreated
with procyanidol oligomers (PCO) was resistant to the hydrolysis induced
by both porcine pancreatic and human leukocyte elastases.  The
quantitative adsorption of pancreatic elastase was similar on either
untreated or PCO-treated elastin suggesting that the binding of this
compound to elastin increases the non-productive catalytic sites of
elastase molecules.  (+) Catechin-insoluble elastin complexes were
partially resistant to the degradation induced by human leukocyte elastase
but were hydrolyzed at the same rate as untreated samples by a constant
amount of pancreatic elastase.  In addition, the coacervation profile of
kappa-elastin peptides as a function of  temperature is greatly modified
in presence of these flavonoids.  We conclusively evidenced that PCO's
bind to skin elastic fibres when injected intradermally into young
rabbits.  As a result, these elastic fibres were found more resistant to
the hydrolytic action of porcine elastase when injected into the same
site.  These in vivo studies further emphasized the potential effect of
these compounds in preventing elastin degradation by elastase(s) as
occurred in inflammatory processes.

Tixier JM, et al.  Evidence by in vivo and in vitro studies that binding
of pycnogenols to elastin affects its rate of degradation by elastases. 
Biochem Pharmacol 33:3933-3939; 1984.

Administration of procyanidolic oligomers in rats.  Observed effects on
changes in the permeability of the blood-brain barrier

Cerebral microvessel permeability disturbances following rapid injection
of autologous blood into the carotid artery are evidenced in cross
sections of the rat brain by extravascular dye leakage.  Here, Evans blue
was injected intravenously 2 hours after the blood injection and 30
minutes before sacrificing the animals.  Five groups of 10 rats each were
given Procyanidolic Oligomers (PCO) in respective doses of 10, 30, and 300
mg/kg by oral route and 10 and 30 mg/kg by intraperitoneal route.  Three
PCO doses were administered prior to blood injection, on D-2, D-1 and D0. 
At oral doses of 10 and 30 mg/kg, the blue color in the injected
hemisphere was significantly less intense in the treated group than in the
untreated group.  When administered intraperitoneally, PCO showed a
preventative effect on both the degree and extent of lesions.  The
following mechanism of action of PCO has been put forward in this
experimental model: these compounds may increase the resistance of the
tight junctions of arteriolar capillaries, thus interfering with the
sudden rise in pressure at the time of blood injection.

Cahn J, Borzeix MG.  Administration of procyanidolic oligomers in rats. 
Observed effects on changes in the permeability of the blood-brain
barrier.  Sem Hop 59:2031-2034; 1983.