1. J Sex Marital Ther. 2003 May-Jun;29(3):207-13.
Treatment of erectile dysfunction with pycnogenol and L-arginine.
Stanislavov R, Nikolova V.
Seminological Laboratory SBALAG, Maichin Dom, Sofia, Bulgaria. rstanik@abv.bg
Penile erection requires the relaxation of the cavernous smooth muscle,
which is triggered by nitric oxide (NO). We investigated the possibility
of overcoming erectile dysfunction (ED) by increasing the amounts of endogenous
NO. For this purpose, we orally administered Pycnogenol, because it is
known to increase production of NO by nitric oxide syntase together with
L-arginine as substrate for this enzyme. The study included 40 men, aged
25-45 years, without confirmed organic erectile dysfunction. Throughout
the 3-month trial period, patients received 3 ampoules Sargenor a day,
a drinkable solution of the dipeptide arginyl aspartate (equivalent to
1.7 g L-arginine per day). During the second month, patients were additionally
supplemented with 40 mg Pycnogenol two times per day; during the third
month, the daily dosage was increased to three 40-mg Pycnogenol tablets.
We obtained a sexual function questionnaire and a sexual activity diary
from each patient. After 1 month of treatment with L-arginine, a statistically
nonsignificant number of 2 patients (5%) experienced a normal erection.
Treatment with a combination of L-arginine and Pycnogenol for the following
month increased the number of men with restored sexual ability to 80%.
Finally, after the third month of treatment, 92.5% of the men experienced
a normal erection. We conclude that oral administration of L-arginine
in combination with Pycnogenol causes a significant improvement in sexual
function in men with ED without any side effects.
2. Phytother Res. 2003 Jun;17(6):671-4.
Pycnogenol prevents haemolytic injury in G6PD deficient human erythrocytes.
Sharma SC, Sharma S, Gulati OP.
Department of Pharmacology and Therapeutics, Trinity College, Dublin-2
Ireland.
ssharma@tcd.ie
Glucose6 phosphate dehydrogenase (G6PD) deficiency is the most common
X-linked disorder of human erythrocytes where cells have inadequate capacity
to destroy peroxides and high susceptibility towards haemolytic changes.
Pycnogenol is a proprietary dry extract of the French Maritime pine (Pinus
pinaster) bark with high ability to scavenge free radicals. In the present
study we have investigated if Pycnogenol can protect G6PD deficient erythrocytes
against haemolytic cell damage. Venous blood samples were obtained from
six subject of Mediterranean origin with known G6PD deficiency which was
also confirmed with standard techniques. Erythrocyte haemolysis in the
presence and absence of Pycnogenol was induced either with tert-butylhydroperoxide
(t-BHP) or quinine and the haemoglobin release in the supernatant was
determined by recording the optical density at 540 nm in a Shimadzu spectrophotometer.
Our results have shown that Pycnogenol has protective action against a
Xenobiotic chemical induced haemolysis in G6PD deficient human erythrocytes.
Copyright 2003 John Wiley & Sons, Ltd.
3. J Biochem Mol Toxicol. 2003;17(3):193-9.
Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced
diabetic rats.
Maritim A, Dene BA, Sanders RA, Watkins JB 3rd.
Moi University Faculty of Health Sciences, Eldoret, Kenya.
Free radicals and oxidative stress have been implicated in the etiology
of diabetes and its complications. This in vivo study has examined whether
subacute administration of pycnogenol, a French pine bark extract containing
procyanidins that have strong antioxidant potential, alters biomarkers
of oxidative stress in normal and diabetic rats. Diabetes was induced
in female Sprague-Dawley rats by a single injection of streptozotocin
(90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body
weight, increased serum glucose concentrations, and an increase in liver
weight, liver/body weight ratios, total and glycated hemoglobin, and serum
aspartate aminotransferase activity. Normal and diabetic rats were treated
with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol
treatment significantly reduced blood glucose concentrations in diabetic
rats. Biochemical markers for oxidative stress were assessed in the liver,
kidney, and heart. Elevated hepatic catalase activity in diabetic rats
was restored to normal levels after pycnogenol treatment. Additionally,
diabetic rats treated with pycnogenol had significantly elevated levels
of reduced glutathione and glutathione redox enzyme activities. The results
demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms
in streptozotocin-induced diabetic rats. Copyright 2003 Wiley Periodicals,
Inc. J Biochem Mol Toxicol 17:193-199, 2003; Published online in Wiley
InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10078
4. J Med Food. 2001 Winter;4(4):201-209.
Pycnogenol((R)) in the Management of Asthma.
Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR.
College of Public Health and School of Medicine, The University of Arizona,
1501 N. Campbell Ave., Tucson, AZ 85724.
Asthma is characterized as a chronic inflammatory process. Pycnogenol((R)),
a bioflavonoid mixture extracted from Pinus maritima, is known to scavenge
free radicals while possessing antioxidant and antiinflammatory properties.
The objective of this study was to evaluate the efficiency of this agent
in a randomized, double-blinded, placebo-controlled, crossover study in
patients with varying asthma severity. Twenty-six patients who fulfilled
the American Thoracic Society criteria for asthma were enrolled in the
study. Medical history, physical examination, blood sample analyses, and
spirometric values were obtained at baseline, 4 weeks, and 8 weeks. The
patients were randomly assigned to receive either 1 mg/lb/day (maximum
200 mg/day) Pycnogenol or placebo for the first period of 4 weeks and
then crossed over to the alternate regimen for the next 4 weeks. No adverse
effects were observed related to the study drug. Within the contingent
of 22 patients who completed the study, almost all responded favorably
to Pycnogenol in contrast to placebo. Pycnogenol treatment also significantly
reduced serum leukotrienes compared with placebo. The results of this
pilot study indicate that Pycnogenol may be a valuable nutraceutical in
the management of chronic asthma. We recommend that further clinical trials
be conducted in larger groups of asthmatics to establish its efficacy.
5. Phytother Res. 2003 Jan;17(1):66-9.
Pycnogenol inhibits the release of histamine from mast cells.
Sharma SC, Sharma S, Gulati OP.
Department of Pharmacology and Therapeutics, Trinity College, Dublin-2,
Ireland. ssharma@tcd.ie
Oxygen derived free radicals are now increasingly regarded as a primary
force of tissue destruction and also have the ability to release histamine
from mast cells. Pycnogenol is an extract of the bark of French maritime
pine (Pinus pinaster) containing bioflavonoids with a potent ability to
scavenge free radicals. Therefore Pycnogenol was investigated for inhibition
of histamine release from rat peritoneal mast cells. In addition, its
effects were compared with sodium cromoglycate, a known inhibitor of histamine
release from the mast cell. Rat peritoneal mast cells were isolated and
purified by differential centrifugation and cells pooled from 3-4 animals
were suspended at approximately 10(6) cells/mL buffered salt solution.
Histamine release was induced by compound 48/80 or the calcium ionophore
A-23187 and estimated from supernatant following extraction and by fluorimetric
methods. Pycnogenol produced a concentration dependent inhibition of histamine
release induced by the two secretagogues. Its inhibitory effect on mast
cell histamine release was favourably comparable to sodium cromoglycate.
Copyright -Copyright 2003 John Wiley & Sons, Ltd
6. J Am Diet Assoc. 2003 Jan;103(1):67-72.
Pycnogenol does not impact the antioxidant or vitamin C status of healthy
young adults.
Silliman K, Parry J, Kirk LL, Prior RL.
Department of Biological Sciences (Program in Nutrition and Food Science),
California State University, Chico 95929, USA.
OBJECTIVE: The objectives of this study were to determine if Pycnogenol
(PYC), a water-processed extract made from the bark of Pinus maritima,
interacts with vitamin C to increase its concentration and to increase
total antioxidant capacity of serum and urine. DESIGN: The study design
was a nonrandom intervention. SUBJECTS: Subjects (N=27; 15 women, 12 men)
were aged 19 to 42 years. INTERVENTION: Subjects consumed a placebo twice
daily with meals for the first 2 weeks (baseline) and PYC (200 mg/day)
for the second 2 weeks. Main outcome measures On days 15 and 29, subjects
had a fasting blood sample collected and then consumed a daily dose of
placebo or PYC with a 310-calorie beverage. One hour later a second blood
sample was collected. Blood samples were analyzed for vitamin C and total
antioxidant capacity using the ORAC (oxygen radical absorbance capacity)
assay. Twenty-four-hour urine samples were collected on days 14-15 and
28-29 and analyzed for total phenolics, FRAP (ferric reducing antioxidant
potential), and ORAC. Statistical analyses Paired t tests were used to
test the impact of PYC on the outcome variables. A univariate ANOVA was
used to determine the influence of gender. Pearson's correlation analysis
was used to explore the relationships between dietary factors and outcome
measures. RESULTS: There was no apparent increase in fasting vitamin C
concentration (P=.18) 2 weeks after supplementing the diet with PYC. Fasting
ORAC values actually declined (P=.005). One hour after the ingestion of
a daily dose of placebo or PYC, the total antioxidant capacity of serum
increased by 15% to 19%, but the increase after ingesting PYC was not
significantly (P=.80) more than after placebo. Antioxidant results from
24-hour urine samples were similar. APPLICATIONS/CONCLUSIONS: The present
findings fail to support the vitamin C or antioxidant claims made for
PYC. PYC does not impact the antioxidant or vitamin C status of healthy
young adults.
7. Int Ophthalmol. 2001;24(3):161-71.
Pycnogenol for diabetic retinopathy. A review.
Schonlau F, Rohdewald P.
Institute of Pharmaceutical Chemistry, Westfalische Wilhelms Universitat
Munster, Germany.
Diabetic retinopathy represents a serious health threat to a rapidly growing
number of patients with diabetes mellitus. The retinal microangiopathy
is characterised by vascular lesions with exudate deposits and haemorrhages
causing vision loss. Pycnogenol, a standardised extract of the bark of
the French maritime pine (Pinus pinaster), is known to increase capillary
resistance. Pycnogenol has been tested for treatment and prevention of
retinopathy in five clinical trials with a total number of 1289 patients
since the late 1960's. All but one of these studies have been reported
in French and German and, today, are of limited accessibility, giving
the impetus for reviewing them in detail in this article. There were two
open case studies and two double blind studies (one controlled against
calcium dobesilate and another against placebo) and, finally, one multi-center
field study with 1169 diabetics. All of these studies unequivocally showed
that Pycnogenol retains progression of retinopathy and partly recovers
visual acuity. Treatment efficacy of Pycnogenol was at least as good as
that of calcium dobesilate. Pycnogenol was shown to improve capillary
resistance and reduce leakages into the retina. Tolerance was generally
very good and side effects were rare, mostly referring to gastric discomfort.
In conclusion, treatment with Pycnogenol had a favourable outcome in the
majority of the patients with diabetic retinopathy.
8. Phytother Res. 2002 Sep;16(6):567-71.
Treatment of melasma with Pycnogenol.
Ni Z, Mu Y, Gulati O.
Beijing PHT Nutriment Science Technology Development Co. Ltd, Xiyuan Hospital
of China Academy of Traditional Chinese Medicine, Institute of Food Safety
Control and Inspection, Ministry of Public Health, Beijing, P R China.
Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation
predominantly affecting sun-exposed areas in women. The pathogenesis of
melasma is not fully understood and treatments are frequently disappointing
and often associated with side effects.Pycnogenol is a standardized extract
of the bark of the French maritime pine (Pinus pinaster), a well-known,
potent antioxidant. Studies in vitro show that Pycnogenol is several times
more powerful than vitamin E and vitamin C. In addition, it recycles vitamin
C, regenerates vitamin E and increases the endogenous antioxidant enzyme
system. Pycnogenol protects against ultraviolet (UV) radiation. Therefore
its efficacy in the treatment of melasma was investigated.Thirty women
with melasma completed a 30-day clinical trial in which they took one
25 mg tablet of Pycnogenol with meals three times daily, i.e. 75 mg Pycnogenol
per day. These patients were evaluated clinically by parameters such as
the melasma area index, pigmentary intensity index and by routine blood
and urine tests.After a 30-day treatment, the average melasma area of
the patients decreased by 25.86 +/- 20.39 mm(2) (p < 0.001) and the
average pigmentary intensity decreased by 0.47 +/- 0.51 unit (p < 0.001).
The general effective rate was 80%. No side effect was observed. The results
of the blood and urine test parameters at baseline and at day 30 were
within the normal range. Moreover, several other associated symptoms such
as fatigue, constipation, pains in the body and anxiety were also improved.To
conclude, Pycnogenol was shown to be therapeutically effective and safe
in patients suffering from melasma. Copyright 2002 John Wiley & Sons,
Ltd.
9. Phytomedicine. 2002 Jul;9(5):414-8.
Effect of PYCNOGENOL on the toxicity of heart, bone marrow and immune
organs as induced by antitumor drugs.
Feng WH, Wei HL, Liu GT.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking
Union of Medical College, Beijing, People's Republic of China.
PYCNOGENOL is a mixture of water-soluble bioflavonoids extracted from
the bark of pine trees growing in the southwest coastal region of France.
In the present paper the effects of PYCNOGENOL (Pyc) on the toxicity of
bone marrow, heart and immune organs induced by anticancer drugs were
investigated, in mice. The following results were obtained: 1. Pyc at
the orally-administered dose of 200 and 150 mg/kg body wt. markedly prevented
the elevation of serum creatine phosphokinase (CPK) activity and the decrease
of heart rate in mice treated with doxorubicin (Dox); 2. Pyc at 100 and
150 mg/kg body wt. significantly antagonized the inhibition of DNA synthesis
in thymus induced by subcutaneous injection of cyclophosphamide (Cyc);
3. Pyc at 150 and 200 mg/kg body wt. markedly induced increase of erythrocytes
and hemoglobin, but had no effect on leukopenia, in Cyc-treated mice;
and 4. Pyc has no antagonizing effect on the anticancer activity of Dox
and Cyc. All the results suggest that Pyc possesses a protective effect
on the cardiotoxicity of Dox and the inhibition of thymus DNA synthesis
induced by Cyc in mice.
10. Phytomedicine. 2002 Jul;9(5):410-3.
PYCNOGENOL chewing gum minimizes gingival bleeding and plaque formation.
Kimbrough C, Chun M, dela Roca G, Lau BH.
School of Dentistry, Loma Linda University, California, USA.
PYCNOGENOL is an antioxidant phytochemical shown to have antiinflammatory
activity in both the in vitro and in vivo models. This study compared
the effects of chewing gums with and without PYCNOGENOL on gingival bleeding
and plaque formation in 40 human subjects. In this double-blind study,
subjects were assigned randomly to receive either control gums without
PYCNOGENOL or experimental gums containng 5 mg PYCNOGENOL. Subjects used
chewing gums for 14 days. Gingival bleeding and plaque scores were taken
before and after the experiment. PYCNOGENOL chewing gums significantly
reduced gingival bleeding, while no changes were noted in bleeding indexes
in control subjects who used regular chewing gums. Subjects using regular
control gums had significant increases of dental plaque accumulation during
the two-week period. No increases in plaque accumulation were noted in
subjects using PYCNOGENOL chewing gums. The data of this study suggest
that the use of Pycnogenol chewing gums can minimize gingival bleeding
and plaque accumulation.
11. J Atten Disord. 2002 Sep;6(2):49-60.
An experimental comparison of Pycnogenol and methylphenidate in adults
with Attention-Deficit/Hyperactivity Disorder (ADHD).
Tenenbaum S, Paull JC, Sparrow EP, Dodd DK, Green L.
The Attention Deficit Center in St. Louis 63141, MO.
Twenty-four adults (24 to 53 years old) with Attention-Deficit/Hyperactivity
Disorder (ADHD), Combined Type, were studied in a double-blind, placebo-controlled,
crossover study of Pycnogenol and methylphenidate. Pycnogenol is an antioxidant
derived from the bark of the French maritime pine tree. Methylphenidate
is a standard pharmaceutical intervention for ADHD. Anecdotal reports
suggest that Pycnogenol improves concentration in adults with ADHD without
adverse side effects. Participants received Pycnogenol, methylphenidate,
and placebo, each for three weeks, in a randomized and counterbalanced
order. Although ADHD symptoms improved during treatment, neither methylphenidate
nor Pycnogenol outperformed the placebo control, as measured by self-report
rating scales, rating scales completed by the individual's significant
other, and a computerized continuous performance test. The conservative
dosage levels and relatively brief length of treatment may have contributed
to the absence of significant differences among treatment conditions.
Implications for future research are noted.
12. Growth Horm IGF Res. 2002 Feb;12(1):34-40.
Kyolic and Pycnogenol increase human growth hormone secretion in
genetically-engineered keratinocytes.
Buz'Zard AR, Peng Q, Lau BH.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, Loma Linda, CA 92350, USA.
The amount of human growth hormone (HGH) decreases significantly after
the age of 30. This decrease has been implicated as one of the major causes
in the signs of aging, such as thinning of the skin and bones, a decrease
in lean muscle mass and an increase in adipose tissue. Supplementing the
body's dwindling supply with recombinant human growth hormone (rHGH) has
been shown to reverse the signs and symptoms of aging. However, drawbacks
in rHGH replacement therapy include prohibitively high cost, the need
for repeated injection and side effects such as carpel tunnel syndrome,
gynecomastia and insulin resistance. The purpose of this study was to
establish an in vitro model using genetically-engineered keratinocytes
to screen natural compounds for the ability to stimulate HGH secretion.
We now report that a combination of equal amounts of L-arginine and L-lysine,
aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly
increased secretion of HGH in this in vitro model. The data indicate that
this in vitro model may be used to screen for other secretagogues.
13. Brain Res Mol Brain Res. 2002 Jul 15;104(1):55-65.
Pycnogenol protects neurons from amyloid-beta peptide-induced apoptosis.
Peng QL, Buz'Zard AR, Lau BH.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, Loma Linda, CA 92350, USA.
Neuronal apoptosis is one of the pathological features of Alzheimer's
disease (AD). Morphological pathology reveals that neuronal apoptosis
is associated with senile plaques containing amyloid-beta peptide (Abeta)
in AD brains. Reactive oxygen species (ROS) has been proposed to be involved
in the apoptotic mechanism of Abeta-mediated neurotoxicity. In the present
study, using a rat pheochromocytoma (PC12) cell line, we investigated
the effect of Pycnogenol (PYC), a potent antioxidant and ROS scavenger,
on Abeta(25-35)-induced apoptosis and ROS generation. We used vitamin
E, a known antioxidant agent, to verify the effect of PYC. Abeta(25-35)-induced
apoptosis in PC12 cells was demonstrated by: (1) a dose-dependent loss
of cell viability; (2) a time- and dose-dependent increase in the apoptotic
cells; (3) an induction of DNA fragmentation; and (4) an increase in caspase-3
activity and cleavage of poly (ADP-ribose) polymerase (PARP). Our data
showed that a significant increase in ROS formation preceded apoptotic
events after PC12 cells were exposed to Abeta(25-35). We further found
that PYC not only suppressed the generation of ROS but also attenuated
caspase-3 activation, DNA fragmentation, PARP cleavage, and eventually
protected against Abeta-induced apoptosis. Vitamin E also suppressed cell
death and caspase-3 activation induced by Abeta(25-35). Taken together,
these results suggest that ROS may be involved in Abeta-induced apoptosis
in PC12 cells. They further suggest that PYC can reduce apoptosis, possibly
by decreasing free radical generation in PC12 cells.
14. Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68.
A review of the French maritime pine bark extract (Pycnogenol), a herbal
medication with a diverse clinical pharmacology.
Rohdewald P.
Institute Pharmaceutical Chemistry, Westfalische Wilhelms-Universitat
Munster, Germany. rohdewa@uni-muenster.de
OBJECTIVES: An increasing body of evidence indicates that Pycnogenol (PYC),
a standardized extract of French maritime pine bark, has favorable pharmacological
properties. This is a review of studies with both PYC and components of
the preparation, that have helped to elucidate target sites and possible
mechanisms for activity in men. METHODS: Studies appearing in peer reviewed
literature, as well as results presented at international meetings not
yet available as published papers, are included in this review. Additional
data from published sources in German and French languages that are not
widely available are also included. RESULTS: Chemical identification studies
showed that PYC is primarily composed of procyanidins and phenolic acids.
Procyanidins are biopolymers of catechin and epicatechin subunits which
are recognized as important constituents in human nutrition. PYC contains
a wide variety of procyanidins that range from the monomeric catechin
and taxifolin to oligomers with 7 or more flavonoid subunits. The phenolic
acids are derivatives of benzoic and cinnamic acids. The ferulic acid
and taxifolin components are rapidly absorbed and excreted as glucuronides
or sulphates in men, whereas procyanidins are absorbed slowly and metabolized
to valerolactones which are excreted as glucuronides. PYC has low acute
and chronic toxicity with mild unwanted effects occurring in a small percentage
of patients following oral administration. Clinical studies indicate that
PYC is effective in the treatment of chronic venous insufficiency and
retinal micro-hemorrhages. PYC protects against oxidative stress in several
cell systems by doubling the intracellular synthesis of anti-oxidative
enzymes and by acting as a potent scavenger of free radicals. Other anti-oxidant
effects involve a role in the regeneration and protection of vitamin C
and E. Anti-inflammatory activity has been demonstrated in vitro and in
vivo in animals. Protection against UV-radiation-induced erythema was
found in a clinical study following oral intake of PYC. In asthma patients
symptom scores and circulating leukotrienes are reduced and lung function
is improved. Immunomodulation has been observed in both animal models
as well as in patients with Lupus erythematosus. PYC antagonizes the vasoconstriction
caused by epinephrine and norepinephrine by increasing the activity of
endothelial nitric oxide synthase. Dilation of the small blood vessels
has been observed in patients with cardiovascular disease, whereas in
smokers, PYC prevents smoking-induced platelet aggregation and reduces
the concentration of thromboxane. The ability to inhibit angiotensin-converting
enzyme is associated with a mild antihypertensive effect. PYC relieves
premenstrual symptoms, including abdominal pain and this action may be
associated with the spasmolytic action of some phenolic acids. An improvement
in cognitive function has been observed in controlled animal experiments
and these findings support anecdotal reports of improvement in ADHD patients
taking PYC supplements. CONCLUSIONS: There is much evidence showing that
PYC has beneficial effects on physiological functions. Results from ongoing
clinical research are required to confirm and extend previous observations.
15. Phytother Res. 2002 Mar;16 Suppl 1:S1-5.
Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency.
Koch R.
Wolfsschlucht 6a, 34117 Kassel, Germany.
The aim of this study was to compare the efficacy of Venostasin (horse
chestnut seed extract) and Pycnogenol (French maritime pine bark extract)
in the treatment of chronic venous insufficiency (CVI). In an open, controlled
comparative study 40 patients with diagnosed CVI were treated either with
600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over
a period of 4 weeks. The following parameters were investigated before
the start of treatment and after 2 and 4 weeks of treatment: circumference
of the lower legs and rating of subjective symptoms (scores) of pain,
cramps, night-time swelling, feeling of "heaviness", and reddening
of the skin. In addition, blood levels of cholesterol LDL and HDL were
determined before and at the end of treatment. Pycnogenol significantly
reduced the circumference of the lower limbs and significantly improved
subjective symptoms. Furthermore, Pycnogenol significantly decreased cholesterol
and LDL values in the blood, whereas HDL remained unaffected. Venostasin
only moderately but not significantly, reduced the circumference of the
lower limbs and marginally improved symptoms. Venostasin had no influence
on the determined lipid values. Both medications were equally well tolerated.
In conclusion, Pycnogenol was found to be more efficacious than Venostasin
for the treatment of CVI. Copyright 2002 John Wiley & Sons, Ltd.
16. Phytother Res. 2001 Dec;15(8):698-704.
Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients.
Stefanescu M, Matache C, Onu A, Tanaseanu S, Dragomir C, Constantinescu
I, Schonlau F, Rohdewald P, Szegli G.
Department of Immunology, Cantacuzino Institute, Splaiul Independentei
103,
Bucharest, Romania.
A pilot study was performed to evaluate the efficacy of Pycnogenol treatment
in systemic lupus erythematosus (SLE) patients. Eleven SLE patients were
treated with first line medication according to disease activity and in
addition, six of them received Pycnogenol and five a placebo. The SLE
disease activity index (SLEDAI), serum anti-dsDNA antibodies, fibrinogen,
C-reactive protein levels, erythrocyte sedimentation rate, production
of reactive oxygen species (ROS) by neutrophils, spontaneous apoptosis
and p56(lck) specific activity in peripheral blood lymphocytes were evaluated.
Pycnogenol treatment determined a significant reduction of ROS production,
apoptosis, p56(lck) specific activity and erythrocyte sedimentation rate.
In addition, the decrease of SLEDAI was significant in the Pycnogenol
treated group compared with the placebo group (p = 0.018). The results
obtained suggest that Pycnogenol could be useful for second line therapy
to reduce the inflammatory feature of SLE. Copyright 2001 John WIley &
Sons, Ltd.
17. Phytother Res. 2001 May;15(3):219-23.
Treatment of vascular retinopathies with Pycnogenol.
Spadea L, Balestrazzi E.
Dipartimento di Discipline Chirurgiche, Cattedra di Clinica Oculistica,
Facolta di Medicina e Chirurgia, Via Vetoio, Coppito 2, L'Aquila, Italy.
The aim of our study was to investigate the effects of Pycnogenol on the
progression of diabetic retinopathy and other vascular retinal disorders.
The study consisted of a double-blind phase in which 20 patients were
recruited and randomly treated with placebo or Pycnogenol (50 mg x 3/day
for 2 months) and an open phase in which another 20 patients were treated
with Pycnogenol at the same dose schedule. In total, 40 patients with
diabetes, atherosclerosis and other vascular diseases involving the retina
were enrolled; 30 of them were treated with Pycnogenol and 10 with placebo.
The results demonstrated a beneficial effect of Pycnogenol on the progression
of retinopathy. Without any treatment (placebo) the retinopathy progressively
worsened during the trial and the visual acuity significantly decreased;
on the contrary, the Pycnogenol-treated patients showed no deterioration
of retinal function and a significant recovery of visual acuity was also
obtained. The fluorangiography showed an improvement of retinal vascularization
and a reduced endothelial permeability and leakage in the Pycnogenol,
but not in the placebo-treated, patients. The ophthalmoscopy and the electroretinogram
(ERG) also confirmed the beneficial effects of Pycnogenol. The mechanism
of action of Pycnogenol may be related to its free radical (FR) scavenging,
anti-inflammatory and capillary protective activities. It has been suggested
that Pycnogenol may bind to the blood vessel wall proteins and mucopolysaccharides
and produce a capillary 'sealing' effect, leading to a reduced capillary
permeability and oedema formation. Copyright 2001 John Wiley & Sons,
Ltd.
18. Free Radic Biol Med. 2000 Jan 15;28(2):219-27.
Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion
of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression.
Bito T, Roy S, Sen CK, Packer L.
Department of Molecular and Cell Biology, University of California, Berkeley
94720-3200, USA.
Expression of intercellular adhesion molecule-1 (ICAM-1) is necessary
for leukocyte/keratinocyte interactions. Upregulation of ICAM-1 expression
in keratinocytes has been observed in several inflammatory dermatoses,
such as psoriasis, atopic dermatitis, and lupus erythematosus. Inflammatory
cytokines, such as interferon-gamma (IFN-gamma), upregulate ICAM-1 expression
in keratinocytes. Because of potent antioxidant and anti-inflammatory
properties of the French maritime pine bark extract, Pycnogenol (Horphag
Research, Geneva, Switzerland), its effects were investigated on the interaction
of T cells with keratinocytes after activation with IFN-gamma and the
molecular mechanisms involved in such interactions. Studies were performed
using a human keratinocyte cell line, HaCaT. Cell adhesion in the presence
of IFN-gamma was studied using a coculture assay. Treatment of HaCaT cells
with 20 U/ml IFN-gamma for 24 h markedly induced adherence of Jurkat T
cells to HaCaT cells. PYC pretreatment (50 microg/ml, 12 h) significantly
inhibited IFN-gamma induced adherence of T cells to HaCaT cells (p <
.01). ICAM-1 plays a major role in the IFN-gamma-induced adherence of
T cells to keratinocytes. Thus, the effect of PYC on IFN-gamma-induced
ICAM-1 expression was investigated as well. Pretreatment of HaCaT cells
with PYC significantly inhibited IFN-gamma-induced expression of ICAM-1
expression in HaCaT cells. The downregulation of inducible ICAM-1 expression
by PYC was both dose and time dependent. A 50 microg/ml dose of PYC and
a 12 h pretreatment time (i.e., before activation with IFN-gamma) provided
maximal (approximately 70%) inhibition of inducible ICAM-1 expression
in HaCaT cells. Gamma-activated sequence present on the ICAM-1 gene confers
IFN-gamma responsiveness in selected cells of epithelial origin (e.g.,
keratinocytes) that are known to express ICAM-1 on activation with IFN-gamma.
Gel-shift assays revealed that PYC inhibits IFN-gamma-mediated activation
of Stat1, thus suggesting a transcriptional regulation of inducible ICAM-1
expression by PYC. These results indicate the therapeutic potential of
PYC in patients with inflammatory skin disorders.
19. J Agric Food Chem. 2000 Nov;48(11):5630-9.
Enzyme inhibition and protein-binding action of the procyanidin-rich french
maritime pine bark extract, pycnogenol: effect on xanthine oxidase.
Moini H, Guo Q, Packer L.
Department of Molecular and Cell Biology, 251 Life Sciences Addition,
University of California at Berkeley, Berkeley, California 94720-3200,
USA.
Pycnogenol, an extract from French maritime pine bark (PBE), is a complex
mixture of bioflavonoids with reported protective effects against disease.
PBE is an effective scavenger of reactive oxygen species, and its main
constituents are procyanidins of various chain lengths. To find out the
biochemical basis of action of PBE on enzyme activity, involvement of
its redox activity and direct binding to the enzyme in its subsequent
action on enzyme activity have been investigated. PBE dose-dependently
inhibited the activities of xanthine oxidase, xanthine dehydrogenase,
horseradish peroxidase, and lipoxygenase, but it did not affect the activities
of glucose oxidase, ascorbate oxidase, or elastase. To characterize the
mechanism of PBE action, studies were focused on xanthine oxidase and
glucose oxidase. Under non-denaturing conditions, PBE changed the electrophoretic
mobility of xanthine oxidase but not of glucose oxidase. Gel filtration
chromatography confirmed higher molecular weight complexes of xanthine
oxidase and xanthine dehydrogenase in the presence of PBE. It was found
that hydrophobic bonding might be the dominant mode of interaction between
PBE and xanthine oxidase. The importance of the binding in the effect
of PBE on enzyme activity was supported by the observation that PBE binds
to and inhibits catalase, but not superoxide dismutase. However, no correlation
was found between superoxide/hydroxyl radical scavenging activity and
the inhibitory effect on xanthine oxidase activity of PBE, various purified
flavonoids, or other complex mixtures of bioflavonoids. The results indicate
that PBE selectively inhibits xanthine oxidase through binding to the
enzyme rather than by the redox activity.
20. Phytomedicine. 2000 Oct;7(5):383-8.
PYCNOGENOL in chronic venous insufficiency.
Petrassi C, Mastromarino A, Spartera C.
Cattedra e Scuola di Specializzazione in Chirurgia Vascolare, Dipartimento
di Scienze Chirurgiche, Universita degli Studi di L'Aquila, Italy. chirvasc@cc.univaq.it
The aim of out study was to investigate the efficacy of Pycnogenol - a
French maritime pine bark extract - in the treatment of chronic venous
insufficiency (CVI). The study consisted of a double-blind phase - in
which 20 patients were recruited and randomly treated with placebo or
Pycnogenol (100 mg 2 3/day for 2 months) - and an open phase - in which
other 20 patients were treated with Pycnogenol at the same dose schedule.
In total, 40 patients were enrolled; 30 of them were treated with Pycnogenol
and 10 with placebo. Pycnogenol significantly improved the legs' heaviness
and subcutaneous edema; the venous pressure was also significantly reduced
by the Pycnogenol treatment, thus adding further clinical evidence to
its therapeutic efficacy in patients with CVI. Pycnogenol was effective,
probably by either stabilizing the collagenous subendothelial basal membrane
or scavenging the free radicals, or by a combination of these activities.
Clinically, capillary leakage, perivascular inflammation and subcutaneous
edema were all reduced. The safety of use of Pycnogenol is demonstrated
by the lack of side effects or changes in blood biochemistry and hematologic
parameters. Pycnogenol can be therefore recommended both for prevention
and treatment of CVI and related veno-capillary disturbances.
21. Phytother Res. 2000 Sep;14(6):472-3.
Inhibition of lipogenesis by pycnogenol.
Hasegawa N.
Department of Food and Nutrition, Nagoya Bunri College, Nagoya, Japan.
hsgwn@nagoya-bunri.ac.jp
The influence of pycnogenol on the adipose conversion of 3T3-L1 cells
by insulin was studied. In week 3 of culture with insulin, pycnogenol
was found to inhibit significantly the expression of glycerophosphate
dehydrogenase (p < 0.01). This finding suggests that pycnogenol inhibits
the accumulation of lipid droplets in adipose tissue. Copyright 2000 John
Wiley & Sons, Ltd.
22. Anticancer Res. 2000 Jul-Aug;20(4):2417-20.
Selective induction of apoptosis in human mammary cancer cells (MCF-7)
by pycnogenol.
Huynh HT, Teel RW.
Department of Physiology and Pharmacology, Loma Linda University School
of Medicine, CA 92350, USA.
Breast cancer is the second leading cause of cancer death in women in
the United States. The 1999 Cancer Facts and Figures, published by the
American Cancer Society, estimates that almost 43,700 women and men will
die of breast cancer in the United States. In this study, we compared
the response of human breast cancer cells (MCF-7) and normal human mammary
cells (MCF-10) to apoptosis in the presence of pycnogenol. Pycnogenol
is a mixture of flavonoid compounds extracted from the bark of pine trees.
MCF-7 and MCF-10 cells were plated out in culture dishes and grown in
medium containing 0, 40, or 80 micrograms pycnogenol/ml culture medium.
Cells were harvested at confluency, incubated with DAPI for 15 min and
viewed microscopically for evidence of apoptosis. Apoptosis is detectable
by morphology, chromatin condensation, nuclear DNA fragmentation, DNA
strand breakage or apoptotic bodies. DAPI is a DNA-binding fluorescent
dye used to visualize DNA fragmentation. Apoptosis, as detected by DAPI
staining, was significantly higher in MCF-7 cells treated with pycnogenol
than the untreated cells. The presence of pycnogenol did not significantly
alter the number of apoptotic cells in MCF-10 samples. These results suggest
that pycnogenol selectively induced death in human mammary cancer cells
(MCF-7) and not in normal human mammary MCF-10 cells.
23. Cell Mol Life Sci. 2000 May;57(5):834-41.
Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor
kappa B activation and adhesion molecule expression in human vascular
endothelial cells.
Peng Q, Wei Z, Lau BH.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, California 92350, USA.
The transcriptional regulatory protein nuclear factor kappa B (NF-kappa
B) participates in the control of gene expression of many modulators of
inflammatory and immune responses, including vascular cell adhesion molecule-1
(VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The heightened
expression of these adhesion molecules has been reported to play a critical
role in atherosclerosis, inflammation, ischemic vascular disorders, diabetes,
and cancer metastasis. In the present study, we investigated the effect
of pycnogenol, an antioxidant phytochemical, on the activation of NF-kappa
B and the induction of VCAM-1 and ICAM-1 in tumor necrosis factor (TNF)-alpha-treated
human umbilical vein endothelial cells (HUVECs). Gel-shift analysis of
HUVEC demonstrated that pretreatment with pycnogenol exhibited a concentration-dependent
suppression of TNF-alpha-induced activation of NF-kappa B. Induction of
VCAM-1 and ICAM-1 surface expression by TNF-alpha was dose-dependently
reduced by pycnogenol. TNF-alpha significantly increased the release of
superoxide anion and hydrogen peroxide from HUVECs. Pycnogenol dose-dependently
inhibited their release. The ability of pycnogenol to inhibit NF-kappa
B activation and VCAM-1 and ICAM-1 expression suggests that this phytochemical
may play an important role in halting or preventing the atherogenic process.
24. Biol Pharm Bull. 2000 Jun;23(6):735-7.
Pycnogenol protects vascular endothelial cells from beta-amyloid-induced
injury.
Liu F, Lau BH, Peng Q, Shah V.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, CA 92350, USA.
The neuropathological hallmarks of Alzheimer's disease (AD) are senile
plaques, cerebrovascular beta-amyloidosis, neurofibrillary tangles, and
selective neuronal loss. Beta-amyloid (Abeta) has been shown to cause
vascular damage mediated by generation of reactive oxygen species and
this damage is considered an early event in the development of AD. In
this study, we determined the effect of pyenogenol, a potent antioxidant
phytochemical, on Abeta-induced cellular injury. Pulmonary artery endothelial
cells (PAEC) were exposed to Abeta for 24 h. Cell injury was assessed
by measuring cell viability with methylthiazol tetrazolium (MTT) assay,
and by determining the release of intracellular lactate dehydrogenase
(LDH). Lipid peroxidation products of PAEC were determined by measuring
thiobarbituric acid-reactive substances (TBARS). Exposure of PAEC to Abeta
resulted in a decrease in cell viability, an increase of LDH release indicating
membrane damage, and an elevated level of TBARS. Preincubation of PAEC
with pycnogenol significantly minimized these changes. This study demonstrated
that pycnogenol can protect vascular endothelial cells from Abeta-induced
injury. The data suggest that pycnogenol may be useful for the prevention
and/or treatment of vascular or neurodegenerative diseases associated
with Abeta toxicity.
25. Fitoterapia. 2000 Jun;71(3):236-44.
Pycnogenol in chronic venous insufficiency.
Arcangeli P.
Professore di Clinica Medica Generale e Terapia Medica, Universita degli
Studi di Firenze, Via Marsilio Ficino 10, I-50122, Firenze, Italy.
Forty patients with chronic venous insufficiency (CVI) and varices of
the legs were selected and double-blindly randomly assigned to a treatment
with Pycnogenol (French maritime pine bark extract), 100 mg x 3/day or
a placebo for 2 months, according to a double-blind experimental design.
The effects of the treatment were evaluated by scoring the symptomatology
with a semi-quantitative scale, and the venous blood flow by means of
a hand-held Doppler ultrasound. The tolerability was evaluated by recording
the adverse effects and by means of hematology and blood chemistry parameters,
before and at the end of the treatment. Pycnogenol treatment induced a
significant reduction in subcutaneous edema as well as heaviness and pain
in the legs, on both after 30 and 60 days, the evaluation time periods.
Approximately 60% of patients treated with Pycnogenol(R) experienced a
complete disappearance of edema (the most rapidly disappearing symptom)
and pain at the end of the treatment, while almost all the patients reported
a reduction in leg heaviness which disappeared in approximately 33% of
patients. These changes were statistically significant. No effect was
observed in the placebo-treated subjects. No effect on the venous blood
flow was observed in either of the experimental groups.
26. Phytother Res. 1999 Nov;13(7):619-20.
Stimulation of lipolysis by pycnogenol.
Hasegawa N.
Department of Food and Nutrition, Nagoya Bunri College, Nagoya, Japan.
hsgwn@nagoya-bunri.ac.jp
We studied the influence of pycnogenol on the lipolysis of 3T3 L1 cells
after differentiation. When pycnogenol or epinephrine was exposed to mature
adipocytes, the smaller (less than 20 microm(2)) intracytoplasmic lipid
droplets selectively disappeared. These data suggest that pycnogenol stimulates
lipolysis. Copyright 1999 John Wiley & Sons, Ltd.
27. Thromb Res. 1999 Aug 15;95(4):155-61.
Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol.
Putter M, Grotemeyer KH, Wurthwein G, Araghi-Niknam M, Watson RR, Hosseini
S, Rohdewald P.
Department of Neurology, Westfalische Wilhelms-Universitat Munster, Germany.
The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet
function in humans. Cigarette smoking increased heart rate and blood pressure.
These increases were not influenced by oral consumption of Pycnogenol
or Aspirin just before smoking. However, increased platelet reactivity
yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin
or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American
smokers, blood pressure increased after smoking. It was unchanged after
intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19
American smokers, increased platelet aggregation was more significantly
reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation.
This study showed that a single, high dose, 200 mg Pycnogenol, remained
effective for over 6 days against smoking-induced platelet aggregation.
Smoking increased platelet aggregation that was prevented after administration
of 500 mg Aspirin and 125 mg Pycnogenol. Thus, smoking-induced enhanced
platelet aggregation was inhibited by 500 mg Aspirin as well as by a lower
range of 100-125 mg Pycnogenol. Aspirin significantly (p<0.001) increased
bleeding time from 167 to 236 seconds while Pycnogenol did not. These
observations suggest an advantageous risk-benefit ratio for Pycnogenol.
28. Free Radic Biol Med. 1999 Sep;27(5-6):704-24.
Antioxidant activity and biologic properties of a procyanidin-rich extract
from pine (Pinus maritima) bark, pycnogenol.
Packer L, Rimbach G, Virgili F.
Department of Molecular and Cell Biology, University of California, Berkeley
94720-3200, USA. packer@socrates.berkeley.edu
There is growing interest in the biologic activities of plant extracts
such as that obtained from the bark of the French maritime pine Pinus
maritima, Pycnogenol. Pycnogenol (PYC) is a standardized extract composed
of a mixture of flavonoids, mainly procyandins and phenolic acids. Studies
indicate that PYC components are highly bioavailable. Uniquely PYC displays
greater biologic effects as a mixture than its purified components do
individually indicating that the components interact synergistically.
PYC has been reported to have cardiovascular benefits, such as a vasorelaxant
activity, angiotensin-converting enzyme (ACE) inhibiting activity, and
the ability to enhance the microcirculation by increasing capillary permeability.
Investigations of the cellular mechanisms of these therapeutic effects
have demonstrated that PYC has strong free radical-scavenging activity
against reactive oxygen and nitrogen species. The oligomeric components
of PYC contribute significantly to the ESR free radical signal. PYC also
participates in the cellular antioxidant network as indicated by its ability
to regenerate the ascorbyl radical and to protect endogenous vitamin E
and glutathione from oxidative stress. PYC modulates NO metabolism in
activated macrophages by quenching the NO radical and inhibiting both
iNOS mRNA expression and iNOS activity. The spectrum of different effects
of NO in the circulation and the nervous system suggest the potential
applications of PYC in immune and circulatory disorders as well as in
neurodegenerative disease. PYC can bind to proteins, altering their structure
and thereby modulating the activity of key enzymes and proteins involved
in metabolic pathways. PYC effects redox-sensitive signal transduction
pathways and alters gene expression. Aspects of PYC's activity are presented
and discussed together with possible future implications and directions
in the field of flavonoid research.
29. Anticancer Res. 1999 May-Jun;19(3A):2095-9.
Effects of intragastrically administered Pycnogenol on NNK metabolism
in F344 rats.
Huynh HT, Teel RW.
Department of Physiology and Pharmacology, Loma Linda University School
of Medicine, CA 92350, USA.
NNK is a tobacco-specific nitrosamine that requires metabolic activation
by cytochrome P450 enzymes. NNK may be metabolized via carbonyl reduction,
N-oxidation, and alpha-carbon hydroxylation. Pycnogenol is a mixture of
flavonoid compounds extracted from pine tree bark and is available as
a dietary supplement. We have previously shown that Pycnogenol inhibits
the in vitro metabolism of NNK in lung and liver microsomes of F344 rats
in a concentration-dependent manner. In this report, intragastrically
administered Pycnogenol in saline affected NNK metabolism in lung microsomes
differently than in liver microsomes of F344 rats. The administered Pycnogenol
was inhibitory toward NNK activation in lung microsomes but not in liver
microsomes suggesting that Pycnogenol may afford chemoprotection toward
NNK-induced lung tumorigenesis when administered orally but not toward
NNK-induced liver tumorigenesis. The effects of intragastrically administered
Pycnogenol on NNK metabolism in lung and liver microsomes were similar
in 6 mo and 20 mo old rats although the level of NNK metabolism was less
in the 20 mo old animals.
30. Cancer Lett. 1998 Oct 23;132(1-2):135-9.
Effects of pycnogenol on the microsomal metabolism of the tobacco-specific
nitrosamine NNK as a function of age.
Huynh HT, Teel RW.
Department of Physiology and Pharmacology, Loma Linda University, School
of Medicine, CA 92350, USA.
NNK is a potent environmental carcinogen to which smokers and non-smokers
are exposed. The response to NNK can be altered by various factors including
nutrition. In this study, we examined the effects of pycnogenol on the
in vitro metabolism of the tobacco-specific nitrosamine NNK by liver and
lung microsomes from 6- and 20-month-old male F344 rats. The major NNK
metabolic pathway in liver microsomes was carbonyl reduction, while alpha-hydroxylation
was the major pathway in lung microsomes irrespective of age. Pycnogenol
(40 and 120 microg/ml) exhibited a statistically significant inhibition
of carbonyl reduction and alpha-hydroxylation pathways in liver microsomes
from both age groups and in addition to these pathways, pycnogenol inhibited
the N-oxidation pathway in lung microsomes. The liver and lung microsomes
from 20-month-old rats were less active than from 6-month-old rats although
the difference was not statistically significant.
31. Cell Mol Life Sci. 1998 Oct;54(10):1168-72.
Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated
mice.
Liu FJ, Zhang YX, Lau BH.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, California 92350, USA.
Pycnogenol (procyanidin extracted from Pinus maritima) has been shown
to be a potent free radical scavenger and an antioxidant phytochemical.
The effects of pycnogenol on immune and haemopoietic dysfunction in senescence-accelerated
mice (SAM), as a murine model of accelerated ageing, were determined.
SAMP8, a strain of senile-prone mice, exhibit learning and memory deficits,
immunodeficiency and dysfunction of the haemopoietic system. Oral feeding
with pycnogenol for 2 months significantly improved their T- and B-cell
function. Pycnogenol also augmented the proliferative capacity of haemopoietic
progenitors of bone marrow in SAMP8. These data suggest that pycnogenol
may be useful for either retardation or restoration of parameters associated
with ageing.
32. J Cardiovasc Pharmacol. 1998 Oct;32(4):509-15.
Endothelium-dependent vascular effects of Pycnogenol.
Fitzpatrick DF, Bing B, Rohdewald P.
Department of Pharmacology, University of South Florida, Tampa 33612,
USA.
Pycnogenol (P) is purported to exhibit effects that could be beneficial
in terms of prevention of chronic age-related diseases such as atherosclerosis.
The most studied of these effects is its antioxidant/free radical-scavenging
activity. In this study, we investigated the possibility that this supplement
might produce vascular effects by stimulation of nitric oxide (NO) production
by vascular endothelial cells. In the in vitro experiments, P (1-10 microg/ml)
relaxed epinephrine (E)-, norepinephrine (NE)-, and phenylephrine (PE)-contracted
intact rat aortic ring preparations in a concentration-dependent manner.
However, when the endothelial lining of the aortic ring was removed, P
had no effect, indicating an endothelium-dependent relaxing (EDR) effect.
This EDR response was caused by enhanced NO levels, because the NO synthase
(NOS) inhibitor N-methyl-L-arginine (NMA) reversed (or prevented) the
relaxation, and this response, in turn, was reversed by addition of L-arginine,
the normal substrate for NOS. Pycnogenol-induced EDR persisted after exposure
of intact rings to high levels of superoxide dismutase (SOD), suggesting
that the mechanism of EDR did not involve scavenging of superoxide anion.
In addition to causing relaxation, preincubation of aortic rings with
P (1-10 microg/ml) inhibited subsequent E- and NE-induced contractions
in a concentration-dependent manner. Fractionation of P by Sephadex LH-20
chromatography resulted in three fractions, one of which (fraction 3,
oligomeric procyanidins) exhibited potent EDR activity. These results
indicate that P, in addition to its antioxidant activity, stimulates constitutive
endothelial NOS (eNOS) activity to increase NO levels, which could counteract
the vasoconstrictor effects of E and NE. Furthermore, additional protective
effects could result from the well-established properties of NO to decrease
platelet aggregation and adhesion, as well as to inhibit low-density lipoprotein
(LDL) cholesterol oxidation, all of which could protect against atherogenesis
and thrombus formation.
33. Free Radic Biol Med. 1998 May;24(7-8):1120-9.
Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of
free radical species and modulators of nitrogen monoxide metabolism in
activated murine RAW 264.7 macrophages.
Virgili F, Kobuchi H, Packer L.
Department of Molecular and Cell Biology, University of California, Berkeley
94720-3200, USA.
Nitrogen monoxide (NO) has diverse physiological roles and also contributes
to the immune defense against viruses, bacteria, and other parasites.
However, excess production of NO is associated with various diseases such
arthritis, diabetes, stroke, septic shock, autoimmune, chronic inflammatory
diseases, and atheriosclerosis. Cells respond to activating or depressing
stimuli by enhancing or inhibiting the expression of the enzymatic machinery
that produce NO. Thus, maintenance of a tight regulation of NO production
is important for human health. Phytochemicals have been traditionally
utilized in ways to treat a family of pathologies that have in common
the disregulation of NO production. Here we report the scavenging activity
of Pycnogenol (the polyphenols containing extract of the bark from Pinus
maritima) against reactive oxygen and nitrogen species, and its effects
on NO metabolism in the murine macrophages cell line RAW 264.7. Macrophages
were activated by the bacterial wall components lipopolysaccharide (LPS)
and interferon (IFN-gamma), which induces the expression of large amounts
of the enzyme nitric oxide synthase (iNOS). Preincubation of cells with
physiological concentrations of Pycnogenol significantly decreased NO
generation. It was found that this effect was due to the combination of
several different biological activities, i.e., its ROS and NO scavenging
activity, inhibition of iNOS activity, and inhibition of iNOS-mRNA expression.
These data begin to provide the basis for the conceptual understanding
of the biological activity of Pycnogenol and possibly other polyphenolic
compounds as therapeutic agents in various human disorders.
34. Life Sci. 1996;58(5):PL 87-96.
Immunomodulation by pycnogenol in retrovirus-infected or ethanol-fed mice.
Cheshier JE, Ardestani-Kaboudanian S, Liang B, Araghiniknam M, Chung S,
Lane L, Castro A, Watson RR.
Department of Family and Community Medicine, University of Arizona, Tucson
85724, USA.
Pycnogenol is a commercial mixture of bioflavonoids that exhibits antioxidative
activity. The effects of dietary pycnogenol on immune dysfunction in normal
mice as well as those fed ethanol or infected with the LP-BM5 murine retrovirus
were determined. The ethanol consumption and retrovirus infection caused
abnormalities in the function and/or structure of a broad array of cells
involved in humoral and cellular immunity. Pycnogenol enhanced in vitro
IL-2 production by mitogen-stimulated splenocytes if its production was
suppressed in ethanol-fed or retrovirus-infected mice. Mitogenesis of
splenocytes did not show a significant change in mice treated with pycnogenol.
It reduced the elevated levels of interleukin-6 produced in vitro by cells
from retrovirus infected mice and IL-10 secreted by spleen cells from
mice consuming ethanol. Natural killer cell cytotoxicity was increased
with pycnogenol treatment.
35. Biotechnol Ther. 1994-95;5(3-4):117-26.
Pycnogenol protects vascular endothelial cells from t-butyl hydroperoxide
induced oxidant injury.
Rong Y, Li L, Shah V, Lau BH.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, Loma Linda, California 92350, USA.
The active oxygen induced and free radical mediated oxidation of biological
molecules, membranes, and tissues has been suggested as a major cause
of cancer, atherosclerosis, and aging. Damage of endothelial cells may
lead to cardiovascular and cerebrovascular diseases. In the present study,
the antioxidant effect of pycnogenol (procyanidins extracted from Pinus
maritima) was investigated in vitro using vascular endothelial cells.
Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC)
were preincubated with different concentrations of pycnogenol for 16 h,
washed, and then exposed to an organic oxidant t-butyl hydroperoxide (tBHP)
for 3 or 4 h. Cellular injury was assessed by measuring cell viability
with methylthiazol tetrazolium (MTT) assay and by determining the release
of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products
of PAEC were monitored as malondialdehyde (MDA) with a thiobarbituric
acid fluorometric assay. Incubation of tBHP (75, 100, or 125 microM) with
PAEC decreased cell viability, increased LDH release, and elevated MDH
production. Preincubation of PAEC with pycnogenol (10-80 micrograms/mL)
before tBHP exposure significantly increased cell viability, decreased
LDH release, and reduced MDA production. These results demonstrate that
pycnogenol can protect vascular endothelial cells from oxidant injury.
The data thus suggest that pycnogenol may be useful for the prevention
of disorders associated with oxidative damage.
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