The effect of pycnogenol on lymphatic nodes and adhesion during in a peritoneal adhesion model in rats

Abstract Purpose: To investigate the effects of pycnogenol on peritoneal adhesions and additionally to investigate the immunohistochemical effects of free oxygen radicals and reactive lymph nodes detected in the adhesive tissue that was sampled surrounding the cecum on intra-abdominal adhesions. Methods: Twenty-seven Wistar Albino rats were divided into three groups. In group 1 (sham), laparotomy was performed and stitched up. In group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered 2 cc of saline. In group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Pycnogenol derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum, and the rats were sacrificed. Results: In group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. Conclusions: No positive outcomes indicating that pycnogenol reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Moreover, a significant increase in lymph node size was detected secondary to inflammation. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, pycnogenol increased the production of free oxygen radicals in the tissue.

Inhibitory effects of Pycnogenol®, a pine bark extract, in a rat model of testosterone propionate-induced benign prostatic hyperplasia / 한국실험동물학회지

Benign prostate hyperplasia (BPH) is a male reproductive disease that has gained increasing importance in recent years. The present study investigated whether Pycnogenol® (PYC), a standardized French maritime pine bark extract, could prevent BPH induced by testosterone propionate (TP) in rats. Male Sprague-Dawley rats were randomly divided into five groups of six rats. One group was used as a normal control rats and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. In the two treatment groups, PYC (20 or 40 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the induction of TP. All rats were sacrificed at the scheduled termination time, the prostates were weighed, and histopathologic examinations were conducted. Dihydrotestosterone (DHT) levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 proteins was investigated. BPH-treated animals showed increases in the relative weight of the prostate, higher concentrations of DHT in serum and the prostate, and higher expression of PCNA and Ki-67 in the prostate; in contrast, PYC-treated animals had significant reductions in these factors compared with the BPH animals. These findings indicated that PYC inhibited the development of BPH and that this was closely associated with a reduction in DHT concentration.

Pine bark extract (Pycnogenol®) suppresses cigarette smoke-induced fibrotic response via transforming growth factor-β1/Smad family member 2/3 signaling / 한국실험동물학회지

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

Pycnogenol suppresses TGF-β1-induced hepatic stellate cell activation via ERK-mediated autophagy inhibition / 中国病理生理杂志

AIM:To explore the effect of Pycnogenol on transforming growth factor-β1 ( TGF-β1)-induced he-patic stellate cell activation .METHODS:Cultured LX-2 cells were treated with 5μg/L TGF-β1 and different concentra-tions (0, 10, 25 and 50 mg/L) of Pycnogenol.The viability of the LX-2 cells under the conditions with or without autoph-agy inhibitor 3-MA and ERK inhibitor PD98059 was determined by MTT assay .The protein levels of α-SMA, ColⅠ, TIMP-1, LC3-Ⅱ/Ⅰ, beclin 1, p-ERK1/2 and ERK1/2 were detected by Western blot .RESULTS:Compared with con-trol group, 5μg/L TGF-β1 treatment elevated the cell viability , and increased the protein levels of α-SMA, ColⅠ, TIMP-1, LC3-Ⅱ/Ⅰ, beclin 1, p-ERK1/2, and ERK1/2 in the LX-2 cells (P<0.05).However, these effects were reversed by Pycnogenol pretreatment in a dose-dependent manner and the inhibitory effect of 50 mg/L Pycnogenol was the most sig-nificant in the LX-2 cells (P<0.05).Furthermore, compared with TGF-β1 group, pretreatment with 50 mg/L Pycnog-enol, 5 mmol/L 3-MA or 20 μmol/L PD98059 downregulated TGF-β1-induced cell viability and the protein levels of α-SMA and LC3-Ⅱ/Ⅰ in the LX-2 cells ( P<0.05 ) .CONCLUSION: Pycnogenol suppresses TGF-β1-induced hepatic stellate cell activation via p-ERK and autophagy inhibition .

Pycnogenol attenuates the symptoms of immune dysfunction through restoring a cellular antioxidant status in low micronutrient-induced immune deficient mice

BACKGROUND/OBJECTIVES: We investigated the effect of Pycnogenol (Pyc) on survival and immune dysfunction of C57BL/6 mice induced by low micronutrient supplementation. MATERIALS/METHODS: Female C57/BL/6 mice were fed a diet containing 7.5% of the recommended amount of micronutrients for a period of 12 wks (immunological assay) and 18 wks (survival test). For immunological assay, lymphocyte proliferation, cytokine regulation, and hepatic oxidative status were determined. RESLUTS: Pyc supplementation with 50 and 100 mg.kg(-1).bw.d(-1) resulted in partial extension of the median survival time. Pyc supplementation led to increased T and B cell response against mitogens and recovery of an abnormal shift of cytokine pattern designated by the decreased secretion of Th1 cytokine and increased secretion of Th2 cytokine. Hepatic vitamin E level was significantly decreased by micronutrient deficiency, in accordance with increased hepatic lipid peroxidation level. However, Pyc supplementation resulted in a dose-dependent reduction of hepatic lipid peroxidation, which may result from restoration of hepatic vitamin E level. CONCLUSION: Findings of this study suggest that Pyc supplementation ameliorates premature death by restoring immune dysfunction, such as increasing lymphocyte proliferation and regulation of cytokine release from helper T cells, which may result from the antioxidative ability of Pyc.

Effect of French Maritine Pine Bark Extract on Side Effects of Gynecological Hormonal Therapies / 日本補完代替医療学会誌

<i>Objective</i>: To clarify the effect of Pycnogenol, French maritime pine bark extract, side effects of hormonal therapies.<br> <i>Study Design</i>: Side effects of patients with continuous intake of Pycnogenol during and after Gn-Rh analogue therapy (G group; n=22 (c=14)), moderate (M group; n=21 (c=13)) and low (L group; n=40 (c=23)) dose of cyclic hormonal therapies due to uterine myomas, dysmenorrhea and endometriosis were observed. All subjects provided signed informed consent after understanding the purpose and methods of this study. The ethical committee of Keiju Medical Center approved this study.<br> <i>Result</i>: Continuous intake of Pycnogenol significantly reduced the joint pain, general malaise and dysmenorrhea after the treatment of Gn-Rh analogue and reduced the increase of body weight and edema during the treatments of moderate and low dose of cyclic hormonal therapies.<br> <i>Conclusion</i>: Pycnogenol has preventive effects on the side effect of gynecological hormonal therapies.<br>

Effects of the Mixture of Vitamin C, Vitamin E, Pycnogenol and Evening Primrose Oil on the UV-Induced Pigmentation and Wrinkle Reductions in Human Skin

In this study, the effects of a mixture consisting of vitamin E, vitamin C, pycnogenol and evening primrose oil (mixture LGNC-5) on ultraviolet light (UV) induced pigmentation and wrinkle reductions of normal healthy volunteers were studied. In a double-blind placebo-controlled study, each of 54 subjects took daily either 4 capsules of the mixture LGNC-5 (Group ABC; 282.5 mg/capsule) or placebo (Group Ganada). We irradiated 2.5 MED UV on the upper arms and measured the whitening effect by colorimeter-based L value. The level of wrinkle reduction was determined by image analysis using skin replica around the crow' feet, and the level of serum vitamin E was determined at baseline and 12 weeks. After 12-week oral administration, the treated group showed a significant reduction in skin pigmentation and wrinkles compared with the placebo group (p = 0.011 and p = 0.000005 , respectively). Also, the level of serum vitamin E was significantly increased in the treated group after 12-week oral adminstration of the mixture compared with that in the placebo group (p = 0.0001). In conclusion, 12-week oral administration of LGNC-5 as a dietary supplement could be effective to reduce both UV induced pigmentation and skin wrinkle without side effects.

Pilot Study of Antioxidant Mixture (Vitamin E, Pycnogenol and Squalene) in Healthy Smokers: Inhibitory Effect on Oxidative DNA Damage / 日本補完代替医療学会誌

Oxidative stress is considered to contribute to degenerative disease. The urinary excretion of the DNA repair product 8-hydroxy-2′-deoxyguanosine (8-OHdG) is proposed as a noninvasive biomarker of current oxidative stress <i>in vivo</i>. We investigated the effect of an antioxidant mixture on urinary 8-OHdG excretions in 12 otherwise healthy smokers. During the intervention period for 2 weeks, subjects consumed four capsules of PICACE^® (Pycnogenol^® 15 mg/capsule, Vitamin E; 56.1 mg/capsule, Squalene; 138.9 mg/capsule) per day. On days 0 (pre-internal use), 3, 7, 14, and 44, morning urine samples were collected. The urinary 8-OHdG was measured using high-performance liquid chromatography (HPLC). The urinary 8-OHdG level on day 3 was significantly reduced compared to day 0. The level of 8-OHdG after a washout period for PICACE^® (days 44) returned to day 0 baseline. These preliminary data suggest that PICACE^® supplements can protect smokers from oxidative stress and possibly reduce disease risk caused by free radicals associated with smoking.<br>

Inhibitory effect of pycnogenol on generation of advanced glycation end products in vitro / 中国药理学通报

AIM To investigate the inhibitory effect of pycnogenol on generation of advanced glycation end products (AGEs) in vitro. METHODS Advanced glycation end products were determined by fluorospectrophotometer in the medium of 1 mol?L -1 glucose and 5% bovine albumin incubated at 37℃, 50℃, and 70℃ for different times. The inhibitory effect of pycnogenol was confirmed by the same system incubated with or without pycnogenol at different concentrations. RESULTS The rate of generation of AGEs in vitro was related with incubation time and incubation temperature. The generation of AGEs was inhibited by pycnogenol in vitro. The inhibitory rate was 10%～80% dependent on concentration and incubation time of pycnogenol. The inhibitory effect of pycnogenol on generation of AGEs was almost the same as that of Aminoguanidine at the same concentration. CONCLUSION pycnogenol could significantly inhibit generation of AGEs in vitro.