Palbinone from Paeonia suffruticosa Protects Hepatic Cells via Up‐regulation of Heme Oxygenase‐1

Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases. The pathways by which palbinone (PB) isolated from P. suffruticosa mediates heme oxygenase‐1 (HO‐1) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways. The effect of PB‐treatment on Nrf2 translocalization and HO‐1‐antioxidant response element (ARE) regulation was examined employing Western blot and luciferase assays. PB induced HO‐1 expression via the activation of Nrf2 in the hepatic cells, and ARE‐dependent genes were stimulated via the PB‐mediated Nrf2 activation. PB‐mediated HO‐1 expression could be involved with PI3K/Akt and ERK1/2 pathways. Our study suggests the mechanism by which PB induces HO‐1 expression in the hepatic cells. This might substantiate the traditional applications of P. suffruticosa for the treatment of oxidative stress‐related diseases including oxidant and inflammatory‐mediated vascular and liver diseases. Copyright © 2013 John Wiley & Sons, Ltd.     

Ameliorative Effects of Pine Bark Extract on Spermatotoxicity by α‐Chlorohydrin in Rats

We investigated the protective effects of pine bark extract (Pycnogenol®, PYC, Horphag Research Ltd., Route de Belis, France) against α‐chlorohydrin (ACH)‐induced spermatotoxicity in rats. Rats were orally administered ACH (30 mg/kg/day) with or without PYC (20 mg/kg/day) for 7 days. Administration of ACH significantly decreased sperm motility. α‐Chlorohydrin also caused histopathological alterations and apoptotic changes in caput epididymides. An increased malondialdehyde concentration and decreased glutathione content, as well as catalase and glutathione peroxidase activities were also found. In contrast, PYC treatment significantly prevented ACH‐induced spermatotoxicity, including decreased sperm motility, histopathological lesions, and apoptotic changes in the caput epididymis. Pycnogenol® also had an antioxidant benefit by decreasing malondialdehyde and increasing levels of the antioxidant glutathione and the activities of the antioxidant enzymes catalase and peroxidase in epididymal tissues. These results indicate that PYC treatment attenuated ACH‐induced spermatotoxicity through antioxidant and antiapoptotic effects. Copyright © 2013 John Wiley & Sons, Ltd.     

The effects of the standardized herbal formula PM014 on pulmonary inflammation and airway responsiveness in a murine model of cockroach allergen-induced asthma

Ethnopharmacological relevance

PM014 is a modified form of the Chung-Sang-Bo-Ha-Tang (CSBHT) herbal formula that has been used to treat chronic pulmonary diseases in Korea for centuries. Previously, we developed a formulation of PM014 based on a series of in vitro and in vivo screening efforts that comprises seven herbal extracts. The PM014 formula includes the root of Rehmannia glutinosa, the cortex of Paeonia suffruticosa, the fruit of Schizandra chinensis, the root of Asparagus cochinchinensis, seeds of Prunus armeniaca, the root of Scutellaria baicalensis and the root of Stemona sessilifolia. Asthma is a chronic inflammatory disease of the lungs that is characterized by wheezing, bronchial contraction, and chest tightness. In addition, the airway becomes hypersensitive and narrows through an inflammatory reaction mediated by Th2 cells. The present study was conducted to evaluate the ability of PM014 to prevent allergic airway inflammation and to attenuate airway responses in a cockroach allergen-induced mouse model.

Materials and methods

Mice sensitized to and challenged with cockroach allergen were treated with oral administration of PM014. Airway resistance was determined by whole body plethysmography. In addition, Th2 cytokines and immune cell profiles of bronchoalveolar lavage (BAL) fluid and inflammatory mediators in serum were analyzed by ELISA. A series of histological examinations were also conducted to demonstrate the effects of PM014 on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung.

Results

PM014 significantly inhibited the number of total cells, eosinophils, neutrophils, macrophages and lymphocytes in the BAL fluid of mice that were challenged with cockroach allergen. In addition, PM014 reduced the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the BAL fluid and inflammatory mediators such as IgE in the serum, as measured by enzyme-linked immunosorbent assay (ELISA). Histopathological analysis also showed that PM014 substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy.

Conclusions

In this study, our results indicate that PM014 has significant effects on allergic airway inflammation upon exposure to cockroach allergen in a mouse model. According to these outcomes, PM014 may have therapeutic potential as a treatment for allergic asthma.     

Prevalence and predictors of poor sleep quality in Korean older adults

The purposes of this study were to evaluate the levels of sleep quality and to examine its related factors in the elderly Korean adults. A cross‐sectional research design was used, and 157 adults, aged from 65 to 89, were recruited from five community health centres in Gyeonggi province and Seoul, Korea. All participants were informed about the purpose of the study and were asked to provide demographic characteristics, chronic conditions, self‐rated health, pain, depression, life satisfaction and sleep quality. More than 60% of the participants reported having poor sleep quality. Hierarchical multiple regression analysis showed that age, self‐rated health, pain and depression were related to poor sleep quality. The findings suggest that it is important to screen regularly for sleep quality, and attention to depression, poor self‐rated health and perceived pain were needed to improve sleep quality of older adults.     

Image quality and radiation dose of 128-slice dual-source CT venography using low kilovoltage combined with high-pitch scanning and automatic tube current modulation

To compare vascular enhancement, image quality, and radiation dose of 128-slice dual-source CT venography (CTV) between an imaging setting of 120 kVp with low pitch, and a setting of 100 kVp combined with high pitch and automatic tube current modulation. A total of 100 patients with suspected deep vein thrombosis and varicose veins were divided into two groups: Group 1 [50 patients, 120 kVp, low pitch (0.6), and fixed 120 mA) and Group 2 (50 patients, 100 kVp, high pitch (3.0), and automatic tube current modulation]. Two radiologists, who were blinded to the image protocol, assessed vascular enhancement and image noise in the inferior vena cava (IVC), femoral vein, and popliteal vein. They also assigned an image quality score independently using a 5-point visual scale. Effective dose was estimated using the dose-length product (DLP). Group demographics, radiation dose, vascular enhancement, image noise, and image quality in the two groups were analyzed. Mean vascular enhancement of the IVC, femoral vein, and popliteal vein was significantly higher in group 2 than in group 1, and images in group 2 had significantly higher image noise. However, there were no significant differences in subjective image quality score of the IVC, femoral vein, and popliteal vein. The mean DLP in group 2 (402.10 ± 94.29 mGy cm) was significantly lower than that in group 1 (973.36 ± 63.20 mGy cm) (P < 0.001). Lower extremity CTV using 100 kVp, high pitch (3.0), and automatic tube current modulation improved vascular enhancement with acceptable image quality and low radiation dose.     

Bimodal Perfluorocarbon Nanoemulsions for Nasopharyngeal Carcinoma Targeting

Purpose

The aim of this study was to perform the detection of folate receptor (FR)-positive tumors with a bimodal imaging contrast agent, a perfluorocarbon (PFC)/rhodamine nanoemulsion, providing both ¹⁹F-based magnetic resonance imaging (MRI) and fluorescence imaging capabilities.

Procedures

The PFC/rhodamine nanoemulsion was further infused with phospholipid-anchored folate to improve the ability to target FR-expressing tumors. The preferential accumulation of the FR-targeted bimodal nanoemulsion in FR-positive tumor sites was monitored by both ¹⁹F-MRI and optical imaging.

Results

The FR-targeted PFC nanoemulsion had no significant effect on cell viability, and the size and fluorescence signal of PFC nanoemulsion were very stable. These nanoprobes were successfully delivered into FR-positive tumor xenograft models and showed significantly enhanced signal intensities of ¹⁹F-MRI and fluorescence imaging in the tumor area.

Conclusions

The folate-PFC/rhodamine nanoemulsion has a great potential to serve as a useful optical and ¹⁹F-MRI agent for the diagnosis and targeting of FR-positive tumor.     

Drug delivery system based on responses to an HIV infectious signal

Gene therapy is a growing topic in the medical arena. Since the safety system of gene therapy has not been sufficiently established, its clinical use is limited. Recently, we developed a cell-specific gene regulation system based on a new concept, D-RECS, or Drug and Gene Delivery System Responding to Cellular Signals. We hoped here to apply this D-RECS concept to gene therapy for virus infections. In the present study, we report the design, synthesis and characterization of the functional polymers, which are able to discriminate normal and human immunodeficiency virus type 1 (HIV-1) infected cells. In the D-RECS concept, certain intracellular signals, which are extraordinary activated in the target disease cells specifically, are used as a trigger to activate a transgene expression. Thus, we paid attention to HIV protease as a target signal in this case, because HIV protease is essential for the proliferation of HIV. This protease is therefore an indicator of HIV infection. Two types of polymers were designed and synthesized using methacryloyl peptide and acrylamide with radical copolymerization as a functional gene regulator. The grafted peptide possesses a cationic protein transduction domain (PTD) sequence of HIV-Tat protein, GRKKRRQRRRPPQ for cell permeation, which are connected with polyacrylamide backbone via a consensus substrate sequence for HIV protease, SQNY/PIVQ. At first, the polymers were evaluated to see whether they possess DNA binding ability and HIV protease responsibility using gel retardation assay. The results suggested that a polymer could form a stable complex with DNA and release the DNA specifically responding to HIV protease activity. Furthermore, it was shown that this controlled release of DNA by the HIV protease signal-responsive intelligent polymer actually regulated the gene expression in the cell-free system. This system would be a useful tool for gene therapy in HIV infection, and this methodology will be applicable if the cationic peptide is replaced by another virus-specific protease, which is critical for the replication of a corresponding virus.