Gummy formulations are defined as gradually or slowly released solid oral dosage forms. Risperidone is an atypical antipsychotic medication used to treat schizophrenia and autism-related irritability. This study presents the development of visually appealing, patient-tailored medicated gummies that act as a novel pharmaceutical form of Risperidone for pediatrics. In this study, two gummy bases were used, one containing Glucomannan and the other containing Gelatin as a gelling agent, where these gummy bases were loaded with coated Risperidone pellets with a controlled release layer. The final products were evaluated for their pH, viscosity, content uniformity, drug content, and dissolution profile. Both formulas showed proper rheology and met content and weight uniformity standards. The release rates for F1 and F2 in the acidic media were 25% and 11%, respectively, after 2 h. At the same time, a full-release profile for Risperidone was noticed in both formulae at pH 6.8 where the release lasts for 24 h. It can be concluded that the chewable semi-solid dosages (gummies) filled with coated pellets are suitable for pediatric patients since pediatrics have drug-related problems which can be solved using high gastro-resistance coated pellets, which also shows a proper release profile for the drug.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

BACKGROUND: The leading cause of cancer-related fatalities in women globally is breast cancer. Chemotherapy is one of the traditional therapies for breast cancer, even though it does not target cancer cells directly and has major side effects. As a result, the development of novel therapeutic techniques with improved safety and effectiveness is constantly required.
OBJECTIVE:  This study aimed to investigate the pro-apoptotic and anti-migrative effects of pycnogenol in a breast cancer cell line.
METHODS:  By using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method, the cell viability of breast cancer cells treated with pycnogenol was evaluated. Pycnogenol was applied to the MCF-7 cells in a range of concentrations (20-120 µg/ml) for 24 hours. A phase contrast microscope is used to evaluate changes in cell morphology. In breast cancer cells, acridine orange (AO) and ethidium bromide (EtBr) dual staining were employed to analyze the nuclear morphological alterations. A fluorescent microscope was used to see the apoptotic nuclei. A scratch wound healing assay was performed to evaluate the anti-migrative potential of pycnogenol. Gene expression analysis was performed using quantitative real-time PCR to determine the levels of proapoptotic and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) genes mRNA expression.  Results: In our investigation, breast cancer cells treated with pycnogenol displayed a substantial reduction in cell viability and a statistically significant p<0.05 between the control and treatment groups. We observed inhibitory concentrations (IC-50) at 80 μg/mL in breast cancer cells. After treatment, fewer cells were present, and those that were there shrank and showed cytoplasmic membrane blebbing. Under AO/EtBr staining, treated cells show chromatin condensation and nuclear fragmentation. The results of this study revealed a significant downregulation of Bcl-2, VEGF/FGF, and p53 mRNA expression following treatment with pycnogenol. Furthermore, the impact of pycnogenol on cell migration decreased significantly when compared to control cells. Pycnogenol treatment significantly induces apoptosis and inhibits migration by altering the VEGF signaling pathway.  Conclusion: Overall, this study highlights the promising role of pycnogenol as a proapoptotic and antimigrative agent through the inhibition of anti-apoptotic and VEGF/FGF signaling molecules gene expression, offering new prospects for improving breast cancer treatment.

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 IL1β to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Pycnogenol pretreatment alleviates cisplatin-induced uterine and ovarian injury in rats because of its antioxidative effect.

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.