Integrating network pharmacology and experimental verification to reveal the anti-inflammatory ingredients and molecular mechanism of pycnogenol.

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined. Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments. Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1ß to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

Effects of Pycnogenol® in people with post-COVID-19 condition (PYCNOVID): study protocol for a single-center, placebo controlled, quadruple-blind, randomized trial.

BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC. METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study. DISCUSSION: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.

Review of the pharmacokinetics of French maritime pine bark extract (Pycnogenol®) in humans.

The French maritime pine bark extract Pycnogenol® is a proprietary product from Pinus pinaster Aiton. It complies with the quality specifications in the United States Pharmacopeia monograph "Pine extract" in the section of dietary supplements. Pycnogenol® is standardized to contain 65-75% procyanidins which are a variety of biopolymers consisting of catechin and epicatechin monomeric units. The effects of Pycnogenol® have been researched in a multitude of human studies. The basis for any in vivo activity is the bioavailability of constituents and metabolites of the extract. General principles of compound absorption, distribution, metabolism and elimination as well as specific data from studies with Pycnogenol® are summarized and discussed in this review. Based on plasma concentration profiles it can be concluded that low molecular weight constituents of the extract, such as catechin, caffeic and ferulic acid, taxifolin are readily absorbed from the small intestine into systemic circulation. Procyanidin oligomers and polymers are subjected to gut microbial degradation in the large intestine yielding small bioavailable metabolites such as 5-(3',4'-dihydroxyphenyl)-γ-valerolactone. After intake of Pycnogenol®, constituents and metabolites have been also detected in blood cells, synovial fluid and saliva indicating a substantial distribution in compartments other than serum. In studies simultaneously investigating concentrations in different specimen, a preferential distribution of individual compounds has been observed, e.g., of ferulic acid and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone into synovial fluid compared to serum. The main route of elimination of constituents and metabolites of the French pine bark extract is the renal excretion. The broad knowledge accumulated regarding the pharmacokinetics of compounds and metabolites of Pycnogenol® constitute a rational basis for effects characterized on a cellular level and observed in human clinical studies.

Pycnogenol® French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies.

Pycnogenol® French maritime pine bark extract is a well-known and thoroughly studied patented extract from the bark of Pinus pinaster Ait. ssp. Atlantica. In 39 randomized double-blind, placebo-controlled (RDP) human clinical trials including 2,009 subjects, Pycnogenol® French maritime pine bark extract supplementation for two weeks to six months has been shown to beneficially affect cardiovascular health, chronic venous insufficiency, cognition, joint health, skin health, eye health, women's health, respiratory health and allergies, oral health and sports performance. The mechanisms of action that can explain the respective effects on different conditions in the human body are discussed as well. As investigated in several in vitro, in vivo and in clinical studies, Pycnogenol® French maritime pine bark extract showed antioxidative effects, anti-inflammatory abilities, beneficial effects on endothelial function and reinforcing effects on the extracellular matrix. The present review aims to give a comprehensive overview of currently available "gold standard" RDP trials of Pycnogenol®'s benefits across various health domains compared to placebo. In addition, some of the processes on which the presented effects of Pycnogenol® French maritime pine bark extract are based will be elucidated and discussed. This broad overview of RDP studies on Pycnogenol® in different health domains can be used as a basis for further research on applications and mechanisms of this unique French maritime pine bark extract.

In Vivo Evaluation of Wound Healing Efficacy of Gel-Based Dressings Loaded with Pycnogenol™ and Ceratothoa oestroides Extracts.

Ceratothoa oestroides and French maritime pine bark (Pycnogenol™) extracts are considered promising therapeutic agents in wound healing. This study explores the healing efficacy of composite dressings containing these extracts, aiming to enhance their stability and effectiveness, utilizing a low-temperature vacuum method for producing Sodium Alginate-Maltodextrin gel dressings. Surgical wounds were inflicted on SKH-hr2 hairless mice. Dressings were loaded with Pycnogenol™ and/or C. oestroides extracts and assessed for their efficacy. Wound healing was primarily evaluated by clinical and histopathological evaluation and secondarily by Antera 3D camera and biophysical measurements. Dressings were stable and did not compromise the therapeutic properties of C. oestroides extract. All interventions were compared to the C. oestroides ointment as a reference product. Most of the wounds treated with the reference formulation and the C. oestrodes dressing had already closed by the 15th day, with histological scores of 7 and 6.5, respectively. In contrast, wounds treated with Pycnogenol™, either alone or in combination with C. oestroides, did not close by the end of the experiment (16th day), with histological scores reaching 15 in both cases. Furthermore, treatment with 5% Pycnogenol™ dressing appeared to induce skin thickening and increase body temperature. The study underscores the wound healing potential of C. oestroides extracts and highlights the need for further research to optimize Pycnogenol™ dosing in topical applications.

Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs.

One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.

Enhancement efficiency delivery of antiviral Molnupiravir-drug via the loading with self-assembly nanoparticles of pycnogenol and cellulose which are decorated by zinc oxide nanoparticles for COVID-19 therapy.

The target of the study is to modify the efficiency of Molnupiravir-drug (MOL) for COVID-19 therapy via the rearrangement of the building engineering of MOL-drug by loading it with self-assembly biomolecules nanoparticles (NPs) of pycnogenol (Pyc) and cellulose (CNC) which are decorated by zinc oxide nanoparticles. The synthesis and characterization of the modified drug are performing successfully, the loading and release process of the MOL drug on a nano surface is measured by UV-Vis spectroscopy under room temperature and different pH. The release efficiency of the MOL drug is calculated to be 65% (pH 6.8) and 69% (pH 7.4). The modified MOL drug displays 71% (pH 6.8) and 78% (pH 7.4) for CNC@Pyc.MOL nanocomposite, while CNC@Pyc.MOL.ZnO nanocomposite gave values at 76% (pH 6.8) and 78% (pH 7.4), the efficiency recorded after 19 h. The biological activity of the MOL-drug and modified MOL-drug is measured, and the cytotoxicity is performed by SRB technique, where the self-assembly (CNC@Pyc) appears to be a safe healthy, and high viability against the examined cell line. The antioxidant activity and anti-inflammatory are evaluated, where the nanocomposite that has ZnO NPs (CNC@Pyc.MOL.ZnO) gave high efficiency compared to the composite without ZnO NPs. The CPE-inhibition assay is used to identify potential antivirals against CVID-19 (229E virus), the viral inhibition (%) was reported at 37.6 % (for 800 µg/ml) and 18.02 % (for 400 µg/ml) of CNC@Pyc.MOL.ZnO. So, the modified MOL-drug was suggested as a replacement drug for the therapy of COVID-19 compared to MOL-drug, but the results need clinical trials.

Suppression of dengue virus replication by the French maritime pine extract Pycnogenol®.

Dengue virus (DENV) is mainly found in the tropics and infects approximately 400 million people annually. However, no clinically available therapeutic agents specific to dengue have been developed. Here, we examined the potential antiviral effects of the French maritime pine extract Pycnogenol® (PYC) against DENV because we previously found that the extract exerts antiviral effects on hepatitis C virus, which belongs to the Flavivirus family. First, we examined the efficacy of PYC against DENV1, 2, 3, and 4 serotypes and determined that it had a dose-dependent suppressive effect on the viral load, especially in the supernatant. This inhibitory effect of PYC may target the late stages of infection such as maturation and secretion, but not replication. Next, we examined the efficacy of PYC against DENV infection in type I interferon (IFN) receptor knockout mice (A129). As the propagation of DENV2 was the highest among the four serotypes, we used this serotype in our murine model experiments. We found that PYC significantly inhibited DENV2 replication in mice on day 4 without significantly decreasing body weight or survival ratio. We further examined the mechanism of action of PYC in DENV2 infection by characterizing the main PYC targets among the host (viral) factors and silencing them using siRNA. Silencing long noncoding-interferon-induced protein (lnc-IFI)-44, polycystic kidney disease 1-like 3 (Pkd1l3), and ubiquitin-specific peptidase 31 (Usp31) inhibited the replication of DENV2. Thus, the results of this study shed light on the inhibitory effects of PYC on DENV replication and its underlying mechanisms.

Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.

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.

Spectroscopic study to verify the anti-hepatitis C virus (HCV) treatment through a delivery system of the sofosbuvir drug on chitosan and pycnogenol nanoparticles surface.

The target of the current study is to create a novel hybrid nanocomposite (Cs@Pyc.SOF) by combining the anti-hepatitis C virus (HCV) drug sofosbuvir with the nano antioxidant pycnogenol (Pyc) and nano biomolecules like chitosan nanoparticles (Cs NPs). The characterization procedure works to verify the creation of nanocomposite (NCP) using several different techniques. UV-Vis spectroscopy is used to measure SOF loading efficiency. The various concentrations of the SOF drug were used to determine the binding constant rate Kb, which was found to be 7.35 ± 0.95 min-1 with an 83% loading efficiency. At pH 7.4, the release rate was 80.6% after two hours and 92% after 48 h, whereas at pH 6.8, it was 29% after two hours and 94% after 48 h. After 2 and 48 h, the release rate in water was 38% and 77%, respectively. . The SRB technique for fast screening is used for the cytotoxicity test, where the investigated composites show a safety status and high viability against the examined cell line. The cytotoxicity assay of the SOF hybrid materials has been identified with cell lines like mouse normal liver cells (BNL). So, Cs@Pyc.SOF was recommended as a substitute medication for the therapy of HCV, but the results need clinical studies.

An oral French maritime pine bark extract improves hair density in menopausal women: A randomized, placebo-controlled, double blind intervention study.

Background and Aims: Female pattern hair loss affects females of all ages with a trend to increase after menopause. This disorder may have significant psychological impact and lead to anxiety and depression. Objective: In a single center, double blind, randomized, placebo-controlled study, the effects of oral Pycnogenol® intake (3 × 50 mg/day for a total of 6 months) on hair density, scalp microcirculation, and a variety of skin physiological parameters was studied in Han Chinese menopausal women (N = 76) in Shanghai, China. Methods: Measurements were taken at the beginning and after 2 and 6 months, respectively. Hair density was determined by digital photographs and further evaluated by Trichoscan software. Transepidermal water loss was measured by a humidity sensor in a closed chamber on the skin surface. Changes in microcirculation were detected as resting flux on the scalp by reflection photoplethysmography. Results: Pycnogenol® intake significantly increased hair density by 30% and 23% after 2 and 6 months of treatment, respectively, as detected by Trichoscan® evaluation of digital photographs. Interestingly, photoplethysmography revealed that this beneficial effect was associated with a decrease in resting flux of the scalp skin, which might indicate an improvement of microcirculation. None of these effects were observed in the placebo taking group. In addition, a significant transient decrease of transepidermal water loss was observed in scalp skin under Pycnogenol,® but not placebo treatment. Conclusion: Oral intake of Pycnogenol® might have the potential to reduce hair loss in postmenopausal women.

Targeting Inflammation in the Diagnosis, Management, and Prevention of Cardiovascular Diseases.

Inflammation plays an important role in the development and progression of cardiovascular diseases (CVDs). Hypertension and hyperlipidemia are the key risk factors of CVDs and induce inflammation in the heart and vessels. Unhealthy diet, infection, and smoking coupled with genetic factors lead to the development of CVDs as well as induce inflammation. Risk factors of CVDs such as hypertension and hyperlipidemia along with diabetes activate nuclear factor kappa B, which regulates the transcription of immunoglobulin free light chain (FLC) κ in B cells and the production of multiple inflammatory molecules, leading to inflammation. FLCs are novel biomarkers of inflammation, and their levels have been associated with overall mortality in a general population and with cardiovascular outcomes. In this review, the role of inflammation in the pathogenesis of CVDs, new biomarkers of inflammation, and dietary options counterbalancing inflammatory processes, such as the polyphenol-rich French maritime pine bark extract Pycnogenol, are discussed.

Protective effect of pycnogenol against gamma radiation-induced lung injury in rat: DNA damage, lipid peroxidation, antioxidant levels, and histopathological changes.

Background and Objective: The study aims to evaluate the histopathological changes, enzymatic alterations, and DNA damage in rat lungs induced by whole-body gamma irradiation as well as evaluation of the protective effect of pycnogenol. Materials and Methods: A hundred adult male rats were equally divided into ten groups including control, four antioxidants, γ-irradiation, four antioxidant + γ-irradiations. This study began the day before radiation treatment and continued for 3 days. The pycnogenol was dissolved 5% dimethyl sulfoxide and then administered orally through a gastric tube at a dose of 37.5 mg/kg, 75 mg/kg, 150 mg/kg, and 300 mg/kg in 24, 48, and 72 h before irradiation. Irradiation was applied with a whole-body irradiation dose of 900 cGy in one fraction. DNA damage, histopathological changes, catalase (CAT), and superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in lung tissue of rats were evaluated 3 days after irradiation. Results: CAT and SOD activities were found to be significantly lower in the irradiation group than control (P < 0.001). CAT and SOD activities were higher in the antioxidant + γ-irradiation group than both irradiation and control groups. MDA levels were significantly higher in the irradiation group compared to control (P < 0.001), whereas MDA levels decreased in the antioxidant + γ-irradiation group compared to the irradiation group. The antioxidant groups were significantly increased comet parameters depend on pycnogenol doses compared to control. The antioxidant + γ-irradiation was decreased comet parameter compared to γ-irradiation. As a result of the histopathologically, the antioxidant groups were different than the control group that in the areas of alveolar sacs and connective tissue areas were seen hemorrhage areas similar to the irradiation group. Conclusion: We demonstrate that 300 mg/kg of pycnogenol might provide significant protection against deleterious effects from whole-body ionizing radiation on the lung tissue. P300+ γ-ray group was significantly reduced radiation-induced lung injury and was possible to observe significantly preservation.

Can pycnogenol prevent cisplatin-induced damage in uterus and ovaries?

Introduction: Cisplatin is an antineoplastic agent, which is thought to act on tissues with increased levels of reactive oxygen species and decreased levels of antioxidants. Pycnogenol is a potent antioxidant that is used in medical conditions caused by oxidative stress. The aim of our study is to demonstrate the effects of pycnogenol on cisplatin-induced uterine and ovarian damage in rats. Material and methods: Wistar albino female rats were randomly divided into 3 groups before the experiment as follows: a 2.5 mg/kg cisplatin group (CG; n = 10), a 40 mg/kg pycnogenol + 2.5 mg/kg cisplatin group (PCG; n = 10), and a healthy control group (HG; n = 10). Then, the ovaries and uteri of the rats were examined to determine malondialdehyde (MDA), total glutathione (tGSH) and superoxide dismutase (SOD) biochemical levels and the histopathological findings. Results: Our study demonstrated that, in uterine and ovarian tissues of rats administered with cisplatin, there was a decrease in the levels of tGSH and SOD, while MDA was increased; however, it was observed that these ratios were reversed in the PCG group (p < 0.05). The number of follicles in the ovarian tissues was examined in all 3 groups. When the CG group was compared with the other two groups, the number of primordial, developing and atretic follicles was low, but there was no difference in the corpus luteum count. Conclusions: Pycnogenol pretreatment alleviates cisplatin-induced uterine and ovarian injury in rats because of its antioxidative effect.

The Effect of Herbal Supplements on Blood Pressure: Systematic Review and Meta-Analysis.

Herbal supplements rich in phenolic compounds are evidenced to have a protective effect against cardiovascular diseases. Therefore, they are suggested to be included in diets for people with hypertension (HT). HT is a global health problem and is estimated to affect billions of people until the end of 2025. For this reason, every possible and effective solution preventing HT should be considered. The aim was to perform an updated meta-analysis and review of recently published studies to evaluate the effect of selected herbal supplements on blood pressure reduction. We searched the PubMed database with specified selection criteria, analysing the RCT studies from 2011 to 2021. A total of 31 studies were included in the analysis, and the meta-analysis was conducted on the data from 16 of them. The general effect size of all the supplements via placebo was d = 1.45, p < 0.05 for systolic blood pressure (SBP) and d = 0.31, p < 0.05 for diastolic blood pressure (DBP). The meta-analysis and review of the literature demonstrated that herbal supplements, such as resveratrol, cherry juice, beetroot juice, bergamot extracts, barberry, and pycnogenol, can be effective in blood pressure reduction and cardiovascular prevention, but attention should be paid to their appropriate dosage due to the possibility of side effects from the digestive system.

Protective Effect of Pycnogenol against Methotrexate-Induced Hepatic, Renal, and Cardiac Toxicity: An In Vivo Study.

Methotrexate (MTX) is one of the most commonly used chemotherapies for various types of cancer, including leukemia, breast cancer, hepatocarcinoma, and gastric cancers. However, the efficacy of MTX is frequently limited by serious side effects. Several studies have reported that the cytotoxic effect of MTX is not limited to cancer cells but can also affect normal tissues, leading to prospective damage to many organs. In the present study, we extensively investigated the molecular and microscopic basis of MTX-induced toxicity in different organs (liver, kidney, and heart) and explored the possible protective effect of pycnogenol, a polyphenolic component extracted from the bark of P. pinaster, to attenuate these effects. Biochemical analysis revealed that administration of MTX significantly reduced the function of the liver, kidney, and heart. Histological and immunohistochemical analysis indicated that MTX treatment caused damage to tissues of different organs. Interestingly, administration of pycnogenol (10, 20, and 30 mg/kg) significantly attenuated the deterioration effects of MTX on different organs in a dose-dependent manner, as demonstrated by biochemical and histological analysis. Our results reveal that pycnogenol successfully ameliorated oxidative damage and reduced toxicity, inflammatory response, and histological markers induced by methotrexate treatment. Taken together, this study provides solid evidence for the pharmacological application of pycnogenol to attenuate damage to different organs induced by MTX treatment.

Pycnogenol a promising remedy for diabetic keratopathy in experimentally induced corneal alkali burns in diabetic rats.

AIM: This study aimed to investigate the efficiency of topically applied pycnogenol (PYC) in healing the standardized alkaline corneal ulcer in diabetic and normal rats. MATERIALS AND METHODS: The corneal alkali-burn injury (CA-I) model was unilaterally developed in Wistar rats by filter paper saturated with 0.01 M of NaOH and touching the eyes for 45 s. Rats were divided into four groups: Normal control (NC), normal PYC (NPYC), diabetic control (DC), and diabetic PYC (DPYC). Both NPYC and DPYC groups were daily treated with PY eye drops three times, whereas NC and DC ones were treated with ordinary saline for six successive days. RESULTS: The wound healing of corneal epithelial was improved in the NPYC group compared to the NC group. Meanwhile, it was significantly improved (P < 0.05) in the DPYC group than in the DC group. Histological examination revealed that corneal re-epithelialization was more accomplished in the DPYC group than in the DC group. In addition, the inflammatory cells were augmented in the DC group more than those in the DPYC one. CONCLUSION: The findings obtained revealed the efficiency of PYC for enhancing the corneal re-epithelialization and reducing the inflammatory reaction post alkali burn in rats, and thus it could be beneficially valuable as a treatment for the diabetic keratopathy.

The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects.

The prevalence of chronic diseases has increased significantly with the rising trend of sedentary lifestyles, reduced physical activity, and dietary modifications in recent decades. Inflammation and oxidative stress play a key role in the pathophysiology of several chronic diseases, such as type II diabetes, cardiovascular diseases, and hepatic conditions. Therefore, reducing inflammation and oxidative stress may be beneficial in the prevention and treatment of various chronic disorders. Since chronic diseases are not completely curable, various methods have been proposed for their control. Complementary therapies and the use of natural antioxidant and antiinflammatory compounds are among these novel approaches. Pycnogenol (PYC) is a natural compound that could control inflammation and oxidative stress. Furthermore, some previous studies have shown that PYC could effectively reduce inflammation through signaling the downstream of insulin receptors, inhibiting the phosphorylation of the serine residues of insulin receptor substrate-1, reducing pro-inflammatory cytokines and oxidative stress indices through the stimulation of antioxidant pathways, increasing free radical scavenging activities, preventing lipid peroxidation, and protecting the erythrocytes in glucose-6-phosphate dehydrogenase-deficient individuals, although these effects have not been fully proved. The present study aimed to comprehensively review the evidence concerning the positive physiological and pharmacological properties of PYC, with an emphasis on the therapeutic potential of this natural component for enhancing human health.

Improvement in cardiovascular risk markers by the combined effect of natural polyphenols and vitamins in patients after kidney transplantation.

OBJECTIVES: The aim of this study was to evaluate the potential of supportive therapy by natural polyphenols combined with vitamins C and E on kidney function and risk factors of cardiovascular diseases in renal transplant recipients (RTR). BACKGROUND: Transplant patients have an altered lipid profile associated with the development of cardiovascular disease, which is a major cause of graft loss and mortality in patients. METHODS: The study included 29 renal transplant recipients with mean graft function levels. The lipoprotein (atherogenic and non-atherogenic) subfractions were identified and quantified in plasma by polyacrylamide gel electrophoresis. RESULTS: After supplementation, glomerular filtration rate (GFR) was increased by 8 %, serum creatinine was decreased by 6.7 % and significant changes were found in atherogenic LDL subfractions. The effect of supplementation was observed in arylesterase and lactonase activities of paraoxonase 1 which increased by 9.3 % and 8.1 %, respectively. In addition, significantly decreased levels of neopterin (by 16 %) and asymmetric dimethylarginine (ADMA) (by 7.9 %) were found. CONCLUSION: We could summarize that supportive therapy improves the renal function (GFR, serum creatinine), and reduces the risk of cardiovascular disease by affecting important risk markers of atherosclerosis (lipid profile, paraoxonase 1 activity, neopterin and ADMA) in RTR (Tab. 4, Fig. 1, Ref. 53).

Pycnogenol ameliorates motor function and gene expressions of NF-ƙB and Nrf2 in a 6-hydroxydopamine-induced experimental model of Parkinson's disease in male NMRI mice.

We investigated the effect of Pycnogenol as an antioxidant on improving motor function, depression, and the expression of NF-ƙB and Nrf2 genes in the experimental model of Parkinson's disease. Forty adult male NMRI mice weighing about 30 g were randomly divided into five groups of eight. Saline group: received 3 µl of saline, as 6-hydroxydopamine (6-OHDA) solvent, unilaterally in the left striatum, treatment groups: first received 3 µl 6-OHDA unilaterally inside the ipsilateral striatum and then divided into subgroup A: received distilled water, Pycnogenol solvent, by gavage for 7 days (lesion group), and subgroup B: received Pycnogenol at doses of 10, 20, and 30 mg/kg by gavage for 7 days. Seven days after Parkinson's model induction, the apomorphine test, the degree of catalepsy by bar test, the duration of immobility (depression) by forced swimming test (FST) were measured. In addition, the expression of NF-ƙB and Nrf2 genes was measured using the real-time PCR technique. The total number of rotations in the apomorphine test decreased significantly in the groups receiving Pycnogenol. Administration of Pycnogenol significantly reduced catalepsy. The study of depression in the group receiving Pycnogenol showed a significant reduction. Also, Pycnogenol increased the expression of the Nrf2 anti-inflammatory gene, but it had no significant difference in the expression of NF-ƙB gene. Pycnogenol, presumably with its antioxidative and genomic effects, improves the expression of the anti-inflammatory gene and found that neuroprotection effect in the brain.