Pine Bark (Pycnogenol + Arginine)

BACKGROUND: The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in men and to observe the effect of PAL combined therapy on sexual function in patients with erectile dysfunction (ED), and we hope to provide more choices of drugs for treating patients with ED. METHODS AND ANALYSIS: The study was constructed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched seven databases from inception to 15 February 2023, for a comprehensive search of clinical trials using relevant keywords. Continuous variables in this meta-analysis were calculated using the mean difference and 95% confidence interval. All relevant statistical analyses were performed using RevMan v. 5.4 software. RESULTS: Three studies with 184 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. The results of the current meta-analysis showed that there were significant differences in the international index of erectile function scores (erectile domain), intercourse satisfaction scores, orgasmic function scores, overall satisfaction scores, and sexual desire scores between the combination treatment group and the control group. There was no significant difference in improving the testosterone levels between the two groups. CONCLUSION: These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED. This study will provide clinicians with more options for treating patients with ED. More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/#myprosperoUnique, Identifier: CRD42023411781.

INTRODUCTION: The efficacy and safety of arginine supplements in erectile dysfunction (ED) remain debatable. AIM: To assess the potential role of arginine supplements on ED as alternatives to phosphodiesterase inhibitors. METHODS: Studies published up to April 2018 that evaluated the efficacy of arginine supplements were identified from multiple databases (Google Scholar, PubMed, Medline, Embase, Kiss, DBpia, and Cochrane databases). Studies comparing arginine supplements with placebo or no treatment; focusing only on patients with mild to moderate severity of ED; and presenting outcomes such as improvement rate, International Index of Erectile Function (IIEF) score, and adverse effects were included. Subgroup analysis for arginine alone and arginine in combination with other substances was further conducted to increase interpretability. MAIN OUTCOME MEASURE: The strength of the association between arginine supplements and ED was assessed using relative odds ratios and weighted mean differences with 95% CI. RESULTS: In total, 10 randomized controlled trials met the inclusion criteria, reporting the outcomes of 540 patients with ED. The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44). Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged. The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe. CLINICAL IMPLICATIONS: Arginine supplements can be recommended to patients with mild to moderate ED. STRENGTH & LIMITATIONS: The strength of this study is that it is the first meta-analysis to assess the potential role of arginine supplements in ED compared with placebo or no treatment. A limitation is that the treatment dosage and duration varied among studies, which may have contributed to study heterogeneity. CONCLUSION: The results of our systematic review and meta

BACKGROUND: Nutrition plays an important role in prevention and management of cardiovascular diseases (CVD) in early stages. Recent research demonstrated beneficial effects of various nutritional ingredients on vascular health. The aim of the current study was to evaluate the effects of an L-arginine-based multi ingredient product (AbMIP) on vascular function. METHODS: Twenty-five male and female subjects, aged between 45 and 65 years with elevated blood pressure and hyperhomocysteinemia were included in this cross-over trial. Subjects were randomly assigned to one of the two sequence groups (AbMIP -placebo or placebo - AbMIP). AbMIP and placebo were taken for 4 weeks, each. Endothelial function under fasting conditions, blood pressure, postprandial endothelial function after consumption of a high fat meal, homocysteine, asymmetric dimethyl arginine (ADMA) and Hba1c were determined. RESULTS: AbMIP significantly improved fasting endothelial function determined by EndoPAT™ when compared to placebo (p = 0.047). Similarly, homocysteine levels were significantly decreased after verum supplementation when compared to placebo (p < 0.0001). Systolic blood pressure decreased significantly under AbMIP (p = 0.002) and the reduction was more pronounced when compared to placebo. However, due to placebo-effects no significant difference could be found between groups (p = 0.586). The effects on postprandial endothelial function were stronger for AbMIP when compared with placebo but did not reach significance (p = 0.201). No significant effects of AbMIP were observed regarding HbA1c, ADMA and diastolic blood pressure. CONCLUSIONS: Due to improvement on endothelial function, decrease of elevated homocysteine levels and excellent tolerability, AbMIP was demonstrated to be a beneficial option for dietary treatment of endothelial dysfunction and hyperhomocysteinemia in early stages of CVD. TRIAL REGISTRATION: The clinical trials.gov identifier is NCT02392767 , November 14, 2014.

AIM: Primary objective of the study was the evaluation of effects of a combination of plant extracts and aminoacids on erectile function (ED). METHODS: The study was performed as a randomized, placebo-controlled, double-blind, cross-over study. 50 men with moderate ED received a combination of Pycnogenol®, roburins, L-arginine, L-citrulline or placebo. Sexual wellness was evaluated by the International Index of Erectile Function (IIEF). RESULTS: Treatment over a period of one month restored erectile function to normal. CONCLUSION: The combination offers an option for treatment of ED without unwanted effects.

AIM: The aim of this study was to investigate the influence of Prelox®R, a combination of French maritime pine bark extract (Pycnogenol®), L-arginine, L-citrulline and roburins, on male fertility. METHODS: Sperm quality of 50 subfertile men was tested in monthly intervals in a double-blind, randomized, placebo controlled, crossover study. Patients received 2 tablets Prelox®R or placebo twice daily during test periods. Following a run-in period of 1 month, patients received either Prelox®R or a placebo for 1 month. After a wash-out period of 1 month, patients received Prelox®R or a placebo in a crossover manner for 1 month. Sperm volume, concentration of spermatozoa, total count, motility, vitality and morphology were measured by standard methods of calculation of the Fertility Index (FI) in monthly intervals. Activity of e-NOS in sperm was evaluated in parallel by measuring the quantity of L-citulline produced from L-arginine. RESULTS: Supplementation with Prelox®R enhanced sperm volume and concentration, motility, vitality and morphology significantly versus placebo. The Fertility Index rose to normal values during treatment with Prelox®R. e-NOS activity in sperm was elevated by Prelox®R. No adverse effects were reported. CONCLUSION: Prelox®R offers a safe method to improve quality of human spermatozoa in subfertile men.

AIMS: Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. METHODS AND RESULTS: Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. CONCLUSION: This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

OBJECTIVE: To assess the effects of a complex plant extract (Prelox®, a formulation of pine bark extract and l-arginine aspartate; Horphag Research UK Ltd, London, UK) on erectile dysfunction (ED) in men, as sexual desire typically persists in ageing men, while their erectile and endothelial function gradually declines. PATIENTS AND METHODS: In this double-blind, placebo-controlled study we assessed the effects of Prelox in 124 patients (aged 30-50 years) with moderate ED over an investigational period of 6 months. The International Index Of Erectile Function (IIEF) was used to quantify changes in sexual function. RESULTS: The erectile domain of the IIEF (questions 1-5 plus 15) improved with Prelox from a baseline mean (sd) score of 15.2 (6.6) to 25.2 (2.1) after 3 months and 27.1 (2.1) after 6 months of treatment. In the placebo group there was an increase from a baseline score of 15.1 (7.0) to 19.1 (3.0) and 19.0 (3.1) after 3 and 6 months, respectively. The effects with Prelox were statistically significant compared with placebo (P < 0.05). Mean (SD) total plasma testosterone levels increased significantly from 15.9 (2.3) to 18.9 (2.6) nmol/L (P < 0.05) after 6 months with Prelox, compared to an increase from 16.9 (2.4) to 17.3 (2.3) nmol/L in the placebo group. CONCLUSION: This study shows that Prelox is effective for improving erectile function, and that this effect persists on continuous therapy for up to 6 months. Moreover, there is some evidence that erectile function continues to improve the longer the therapy is used. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

In a randomly allocated, double-blind, placebo-controlled, cross-over design, 50 infertile patients were treated for 1 month with placebo or a combination of l-arginine aspartate and Pycnogenol (Prelox). Semen samples were examined at 4 week intervals according to WHO criteria. Treatment with Prelox increased significantly the semen volume, concentration of spermatozoa, percentage of motile spermatozoa and percentage of spermatozoa with normal morphology compared with placebo. The placebo had no influence on the parameters of seminological analysis. Intake of Pycnogenol for 1 month improved the fertility index to normal values. After treatment, the fertility index decreased again to infertile status. No unwanted effects were reported. Prelox seems to be a promising alternative to treat patients with mild infertility. (c) 2009 John Wiley & Sons, Ltd.

Pycnogenol, an extract of bark from the French maritime pine, Pinus pinaster Ait., consists of a concentrate of water-soluble polyphenols. Pycnogenol contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids. Antioxidants, such as bioflavonoids, enhance endothelial nitric oxide (NO) synthase expression and subsequent NO release from endothelial cells. The purpose of this study was to determine Pycnogenol's effects on endothelium-dependent vasodilation in humans. This was a double-blind, randomized, placebo and active drug study. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol (180 mg/day) (n=8) or placebo (n=8). FBF was measured by using strain-gauge plethysmography. Neither the placebo nor Pycnogenol altered forearm or systemic hemodynamics. Pycnogenol, but not placebo, augmented FBF response to ACh, from 13.1 +/- 7.0 to 18.5 +/- 4.0 mL/min per 100 mL tissue (p<0.05). SNP-stimulated vasodilation was similar before and after 2 weeks of treatment in the control and Pycnogenol groups. The administration of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, completely abolished Pycnogenol-induced augmentation of the FBF response to ACh. These findings suggest that Pycnogenol augments endothelium-dependent vasodilation by increasing in NO production. Pycnogenol would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction.

137. Akush Ginekol (Sofiia). 2007;46(5):7-12. [Sperm parameters in male idiopathic infertility after treatment with prelox]. [Article in Bulgarian] Nikolova V, Stanislavov R, Vatev I, Nalbanski B, Pŭnevska M. The diagnosis of male infertility is determinate after assessment of sperm quality and clinical study. In nearly 30% of the cases nevertheless detailed clinical and laboratory study it can't be discovered the cause and on the bases of exclusion criteria set the diagnosis idiopathic infertility. The object of our study was investigation of the group patients (n=50) with idiopathic infertility treated with Prelox and to be studied its effects on spermatozoa parameters. MATERIAL AND METHODS: The study design was double-blind, placebo-controlled, cross-over, randomized study, including introduction period (1 month), two therapeutic periods (each one of 1 month) separated with 1 month wash out period and concluding period of 1 month. There was applied a new method for treatment with mechanism of action stimulation the production cGMP of spermatozoa endothelial nitric oxide synthase (eNOS). This is not surprising achieving results show improvement of sperm quality. The methods of the study were: 1. Assessment of the conventional semen analysis (according the criteria of WHO, 1999). 2. Spermatozoa function tests. 3. Spermatozoa-cervical mucus penetration tests. RESULTS: The obtained results showed improvement of sperm quality, in the middle-aged men the therapeutic answers was better than in younger. In conclusion the therapy with Prelox improve sperm parameters in men with idiopathic infertility. Pycnogenol (one of the constituents of Prelox) has powerful antioxidative influence ameliorating spermatozoa function.

In a randomly allocated, double-blind, placebo-controlled, crossover design, 50 patients with mild to moderate erectile dysfunction (ED) were treated for 1 month with placebo or a combination of L-arginine aspartate and Pycnogenol (Prelox). Patients reported sexual function from diaries. Testosterone levels and endothelial NO synthase (e-NOS) were monitored along with routine clinical chemistry. Intake of Pycnogenol for 1 month restored erectile function to normal. Intercourse frequency doubled. e-NOS in spermatozoa and testosterone levels in blood increased significantly. Cholesterol levels and blood pressure were lowered. No unwanted effects were reported. Prelox is a promising alternative to treat mild to moderate ED.

BACKGROUND: The aim of this pilot registry study was to use a standardized supplement (Lady Prelox®, Horphag Research) - including Pycnogenol®, l-arginine, L-citrulline and rose hip extract - to improve signs and symptoms associated with vaginal dryness in pre and post-menopausal healthy women. A group of women used only a standard management (SM) and a second group added Lady Prelox®. METHODS: Four groups of women were included in the study. 34 pre-menopausal and 38 post-menopausal women took Lady Prelox®, four tablets daily for 8 weeks and 33 pre-menopausal women and 35 post-menopausal women served as controls. RESULTS: No safety problems were observed with the supplement that was well tolerated. The subgroups of controls and supplemented subjects were comparable in both the pre- and post-menopausal groups. Among pre-menopausal women, results of the female sexual function index (FSFI) were significantly improved with the supplement in comparison with the control subjects' group (P<0.05). The results of the FSFI questionnaire for post-menopausal women indicated a significant improvement at 8 weeks with Lady Prelox® (P<0.05) in comparison with controls. Preclinical items (vaginal dryness, pain/discomfort during intercourse, mucus, minimal infections, presence of candida and oxidative stress) were significantly improved (P<0.05) with Lady Prelox®) in comparison to minimal changes with the SM group. These measurements included all women. CONCLUSIONS: The effects of the supplementation with Lady Prelox® on vaginal dryness were significant. The supplement was well accepted and revealed no side effects or tolerability problems. Further studies are evaluating the effects of Lady Prelox® on other aspects of the menopausal transition that may alter the quality of life of most women in advanced age. A gentle approach with suitable dietary supplementation, represents a promising option for addressing common challenges that women experience in such conditions.

BACKGROUND: This study evaluates the effects of training (on running distance measured with a Cooper test) in 3 weeks in non-professional athletes using PycnoRacer®, a fitness drink (FD) including Pycnogenol® during the training period. METHODS: Pycnogenol® has been used in preclinical conditions and prevention. PycnoRacer® is a liquid combination of Pycnogenol® (15 mg), L-leucine (0.6 g), L-arginine (0.3 g), L-isoleucine (0.3 g), and L-valine (0.3 g). Two comparable groups (one using the FD) were formed: 60 training athletes were requested to drink one bottle 4 times/day, while 65 controls did not use PycnoRacer® or other comparable sports drinks. All subjects had a strong athletic background and advanced knowledge of the procedures of the tests. Two daily training sessions were completed. The sessions consisted in warming up and running a Cooper test. RESULTS: 125 subjects completed the three weeks according to plans. There were nine dropouts due to logistical or working problems. Subjects using the FD improved on average by 18.83% (range 12-23%) in their running distance with training. The difference with controls was significant (P<0.05) at 3 weeks (controls improved on average by 8.9%; range 3-17.4%). The difference between the two groups was on average 9.93% (P<0.05). A comparable increase in VO2max was observed in the groups. In the FD group the increase was on average by 10.05 mL/kg/min compared to 4.95 mL/kg/min in controls, with a difference of 5.1 mL/kg/min (P<0.05). A VAS score showed comparable values. Lower values (concerning muscular pain and cramps) were observed in FD subjects (P<0.05) at the end of the 3 weeks of training. The level of plasma free radicals (PFR) values after the last Cooper test was significantly lower at 3 weeks in the FD group (P<0.05). No intolerance problem was observed by subjects using the FD. CONCLUSIONS: In conclusion, the use of PycnoRacer® improved training, running distance, VO2max and PFR decreasing muscular pain and cramps.

Extension of the healthy life span is of primary importance for the aging society. Among exercise, healthy nutrition, and mental training, food supplements are widely used as preventive measures to postpone the diverse symptoms of aging. The extract from the bark of the French maritime pine, Pycnogenol, rich on flavonoids, has anti-inflammatory and antioxidative property, proven in in vivo studies. The extract reduces oxidative stress and improves endothelial health. Its antithrombotic properties are based on inhibition of platelet aggregation. In double-blind, placebo-controlled clinical studies, Pycnogenol shows diverse positive effects. With respect to cardiovascular symptoms, the extract has an antihypertensive effect, slows down the progression of atherosclerosis, and prevents venous thrombosis. As reported in studies in China and the United States, type 2 diabetes and diabetic retinopathy is improved with Pycnogenol. The extract restores mobility of seniors in case of patients suffering from osteoarthritis, Pycnogenol reduces pain and stiffness and use of analgesics. Furthermore, cognitive functions of elderly people, especially spatial memory, are significantly ameliorated. Climacteric symptoms are significantly alleviated by the pine bark extract. Urinary symptoms of benign prostatic hyperplasia are reduced by Pycnogenol. In combination with L-arginine, Pycnogenol restores erectile function in men with erectile dysfunction. The sum of these positive effects on relevant symptoms of aging suggests using Pycnogenol for a more extended period of healthy aging.

OBJECTIVES: Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys by increasing nitric oxide levels. French maritime pine bark extract Pycnogenol®, which is a potent nitric oxide donor, is reported to be effective for SDys. However, no reports have been published on whether it ameliorates LUTS. DESIGN: Open-labeled, randomized study. The effects of two supplements, Nokogiriyashi EX® containing 160 mg saw palmetto (SP) extract per tablet and Edicare® containing 10 mg of Pycnogenol®, 115 mg of l-arginine and 92 mg of aspartate (PAA) per tablet on International Prostate Symptom Score (IPSS), IPSS-QOL, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urinary 8-OHdG and uroflowmetry (UFM) of total 40 men with LUTS and SDys were examined. RESULTS: 19 subjects were instructed to take two tablets of SP, on the other 20 were on four tablets of PAA for 16 weeks. IPSS and IPSS-QOL showed statistically significant improvements in both groups. OABSS and IIEF5 were significantly improved in the PAA group. Conversely, ICIQ-SF, 8-OHdG and UFM did not change in either group. CONCLUSIONS: PAA might be an effective therapeutic alternative for elderly patients with LUTS and SDys.

We evaluated the effectiveness of antioxidant co-supplementation therapy using Larginine and Pycnogenol(®) in Japanese men with oligoasthenozoospermia and mild erectile dysfunction (ED). A total of forty-seven adult males with oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The effectiveness of supplementation with a combination of L-arginine 690 mg and French maritime pine bark extract (Pycnogenol(®)) 60mg for OAT and ED was investigated. The sperm concentration was enhanced significantly after treatment 2 and 4 months (11.79 ± 9.86 to 21.22 ± 28.17 and 20.15 ± 23.99 × 106/ml). Significant improvements in the International Index of Erectile Function (IIEF) were observed in the total score of IIEF (57.69 ± 11.04 to 59.43 ± 12.57) and domain of Orgasmic Function (9.01 ± 1.92 to 9.34 ± 1.66) after 4 months of treatment. L-arginine acts to increase the production of nitric oxide and Pycnogenol(®) activates the endothelial nitric oxide synthase and it is a potent antioxidant and inhibitor of inducible nitric oxide synthase. This study suggests that the combination of Pycnogenol(®) and L-arginine (Edicare(®)) is helpful for infertile men to ameliorate simultaneously quality of sperms as well as erectile functions.

Beyond the well-known effects on blood pressure (BP) of the dietary approaches to stop hypertension (DASH) and the Mediterranean diets, a large number of studies has investigated the possible BP lowering effect of different dietary supplements and nutraceuticals, the most part of them being antioxidant agents with a high tolerability and safety profile. In particular relatively large body of evidence support the use of potassium, L-arginine, vitamin C, cocoa flavonoids, beetroot juice, coenzyme Q10, controlled-release melatonin, and aged garlic extract. However there is a need for data about the long-term safety of a large part of the above discussed products. Moreover further clinical research is advisable to identify between the available active nutraceuticals those with the best cost-effectiveness and risk-benefit ratio for a large use in general population with low-added cardiovascular risk related to uncomplicated hypertension.

AIM: This supplement study evaluates the Female Sexual Function Index (FSFI) of 100 healthy women (37 to 45 years) with moderate sexual dysfunction who underwent a management program of lifestyle, diet, exercise, and stress control. In association with the management program a group of these women also used the supplement Lady Prelox® in tablets (20 mg Pycnogenol® pine bark extract, 200 mg L-arginine, 200 mg L-citrulline and 50 mg Rosvita® rose hip extract) for eight weeks. METHODS: One group of women was supplemented with Lady Prelox® for 8 weeks. The nine-item FSFI questionnaire was used for evaluation of women's sexual function at inclusion (baseline), after four weeks, and after eight weeks of management and supplementation. Variation in oxidative stress was also evaluated by measuring plasma free radicals. RESULTS: Following supplementation with Lady Prelox® the mean total FSFI scores increased from 14.96±2.68 to 28.25±2.35 after four weeks and 33.91±2.7 after eight weeks. Treatment values were significantly higher than in controls (who used only the management plan) with baseline values of 17.92±2.32 and scores of 23.45±1.82 after four weeks and to 23.52±2.20 after eight weeks. Women in the Lady Prelox® group had an initial value of plasma free radicals (PFR) of 398±29 Carr units: this value decreased to 344:28 at 4 weeks (P<0.05) and 332:31 at 8 weeks (P<0.05). Lower changes were observed in controls with an initial value of 389±33, decreasing to 377±32 (P<0.05) at 4 weeks and to 365; 33 (P<0.05) at 8 weeks (value significantly higher in controls not using Lady Prelox®). The supplementation was well tolerated; no unwanted effects occurred and no women had to stop the supplementation. CONCLUSION: The study suggests that supplementation with Lady Prelox significantly improves sexual function across all domains evaluated by the FSFI in healthy women of late reproductive age. The improvement in FSFI is also associated with a significant decrease in oxidative stress.

Cardiac remodeling is a determinant of the clinical progression of heart failure and now slowing or reversing remodeling is considered as a potential therapeutic target in heart failure. Pycnogenol has been reported to mediate a number of beneficial effects in the cardiovascular system but its effects on hemodynamic and functional cardiovascular changes following cardiac remodeling have not been elucidated. Therefore, we investigated the influence of Pycnogenol supplementation (30 mg/kg) on left ventricular function and myocardial extracellular matrix composition in old C57BL/6N mice following induction of cardiac remodeling by chronic nitric oxide synthase blockade by NG-nitro-L-arginine methyl ester (L-NAME) administration. L-NAME-treated mice demonstrated dilated cardiomyopathy at compensated state, associated with a significant increase of pro-matrix metalloproteinase (MMP)-9 gene expression and activity, a marked decrease in pro-collagen IIIalpha1 gene expression, and a subsequent reduction in cardiac total and cross-linked collagen content. Upon supplementation with Pycnogenol in L-NAME-exposed mice, cardiac gene expression patterns for pro-MMP-2, -9, and -13, and MMP-9 activity were significantly decreased, associated with a significant increase in cardiac tissue inhibitor of metalloproteinase (TIMP)-4 expression. These findings were coincided with a marked increase in myocardial total and cross-linked collagen content, compared with L-NAME-only-treated mice. Moreover, Pycnogenol treatment was associated with reversal of L-NAME-induced alternations in hemodynamic parameters. These data indicate that Pycnogenol can prevent adverse myocardial remodeling induced by L-NAME, through modulating TIMP and MMPs gene expression, MMPs activity, and further reduction in myocardial collagen degradation rate.