Extracts of Phyllostachys pubescens Leaves Represses Human Steroid 5-Alpha Reductase Type 2 Promoter Activity in BHP-1 Cells and Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rat Model.

Benign prostatic hyperplasia (BPH) is the most common symptomatic abnormality of the human prostate characterized by uncontrolled proliferation of the prostate gland. In this study, we investigated the effect of bamboo, Phyllostachys pubescens, leaves extract (PPE) on human 5α-reductase type 2 (SRD5A2) gene promoter activity in human prostate cell lines and the protective effect of PPE on a testosterone-induced BPH rat model. PPE repressed human SRD5A2 promoter activity and its mRNA expression. The rats treated with PPE for 4 weeks showed a significantly attenuated prostate weight compared to vehicle control. PPE-treated rats also showed reduced serum dihydrotestosterone, testosterone, prostate-specific antigen, and SRD5A2 levels by testosterone injection. Quantitative real-time polymerase chain reaction showed that PPE treatment significantly decreased mRNA expression of SRD5A2, androgen receptor (AR), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor 2 compared with the vehicle-treated, testosterone-injected rats in the prostate. Furthermore, PPE treatment showed reduced AR, PCNA, and tumor necrosis factor alpha expression in the prostate via immunohistofluorescence staining. In conclusion, oral administration of PPE prevented and inhibited the development and progression of enlarged prostate lesions in testosterone-induced animal models through various anti-proliferative and anti-inflammatory pharmacological effects and induced suppression of SRD5A2 gene expression.

Augmented Buyang Huanwu Decoction facilitates axonal regeneration after peripheral nerve transection through the regulation of inflammatory cytokine production.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulation Buyang Huanwu Decoction (BYHWD) has been used to treat cardiovascular disorders including cerebral ischemia. Recent studies showed its effects on promoting axonal regeneration after nerve injury. However, compositional reformulation supplemented with herbal components that regulates inflammation may increase its efficacy for nerve repair. AIM OF THE STUDY: We prepared a new herbal decoction by adding selected herbal components to BYHWD (augmented BYHWD; ABHD) and investigated the effect of ABHD on the production of inflammatory cytokines and axonal regeneration using an animal model of nerve transection and coaptation (NTC). MATERIALS AND METHODS: A rat model of NTC was performed on the sciatic nerve. The sciatic nerve and dorsal root ganglion (DRG) were isolated and used for immunofluorescence staining and western blot analysis. DRG tissue was also used to prepare primary neuron culture and the length of neurites was analyzed. Sensorimotor nerve activities were assessed by rotarod and von Frey tests. RESULTS: Three herbal components that facilitated neurite outgrowth were chosen to formulate ABHD. ABHD administration into the sciatic nerve 1 week or 3 months after NTC facilitated axonal regeneration. Cell division cycle 2 (Cdc2) and brain-derived neurotrophic factor (BDNF) proteins were induced from the reconnected distal portion of the sciatic nerve and the levels were further elevated by in vivo administration of ABHD. Phospho-Erk1/2 level was increased by ABHD treatment as well, implying its role in mediating retrograde transport of BDNF signals into the neuronal cell body. Production of inflammatory cytokines IL-1ß and TNF-α was induced in the reconnected nerve but attenuated by ABHD treatment. Behavioral tests revealed that ABHD treatment improved functional recovery of sensorimotor activities. CONCLUSIONS: A newly formulated ABHD is effective at regulating the production of inflammatory cytokines and promoting axonal regeneration after nerve transection and may be considered to develop therapeutic strategies for peripheral nerve injury disorders.

Acupuncture stimulation attenuates TNF-α production via vagal modulation in the concanavalin A model of hepatitis.

BACKGROUND: A growing body of evidence shows that neuronal activity is involved in modulating the efficacy of acupuncture therapy. However, it has been seldom investigated whether neuronal activity following acupuncture stimulation is effective at regulating hepatic inflammation. OBJECTIVE: Using the concanavalin A (ConA) model of hepatitis, we investigated the regulation of inflammatory cytokine tumor necrosis factor (TNF)-α in the liver tissue and the blood after acupuncture stimulation at ST36. METHODS: Mice were subjected to ConA injection, acupuncture stimulation at ST36 by manual acupuncture (MA) or electroacupuncture (EA) procedures, and vagotomy (VNX). Liver tissue and blood were collected for TNF-α analysis. TNF-α mRNA was analyzed by real-time polymerase chain reaction (PCR), and TNF-α, CD11b, CD68, and Erk1/2 proteins were analyzed by Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. RESULTS: TNF-α mRNA and protein were induced in CD11b-positive hepatic cells and the plasma at 6-24 h after ConA injection. The application of MA or EA was very effective at attenuating the production of TNF-α. Anti-inflammatory effects of acupuncture were greatly suppressed by VNX in ConA-injected animals, suggesting the requirement of vagus nerve activity in acupuncture-mediated anti-inflammatory responses. Electrical stimulation of the sciatic nerve (SNS) resulted in an anti-inflammatory effect similar to acupuncture stimulation. In parallel with TNF-α, production of phospho-Erk1/2, which was induced in the liver tissue, was downregulated by MA and EA in liver cells. CONCLUSION: The regulatory effects of acupuncture stimulation on inflammatory responses in the liver may be modulated through the activation of the vagus nerve pathway.

Bogijetong Decoction and Its Selected Formulation Are Involved in Alleviating Neuropathic Pain in a Rat Model of Chronic Constrictive Injury.

Bogijetong decoction (BGJTD) is a formulation that is used for the treatment of neuropathic pain caused by cancer therapy, diabetes, and peripheral nerve injury. In the previous study, we selected four herbal constituents from BGJTD, formulated new decoction (BeD), and demonstrated its efficacy on the neuroprotection of peripheral sciatic nerve in streptozotocin-induced diabetic animals. Here, we report attenuating effects of BGJTD and BeD on neuropathic pain. Neuropathic pain was induced by ligation of the sciatic nerve to generate chronic constrictive injury (CCI). BeD was more effective than BGJTD in alleviating neuropathic pain lasting 3 - 4 weeks after CCI. In vivo administration of BeD did not alter the levels of brain-derived neurotrophic factor (BDNF) which were strongly induced by CCI in the sciatic nerve but downregulated TrkB production in the sciatic nerve. Downregulation of TrkB signals by BeD was confirmed in cultured DRG neurons. BGJTD was more effective in attenuating TNF-α production in the sciatic nerve than BeD, whereas BeD increased IL-6 more efficiently than BGJTD. Furthermore, phopsho-Erk1/2 was increased in the sciatic nerve and dorsal root ganglia (DRG) after BeD treatment. Neurite outgrowth of primary DRG neurons prepared from rats which had undergone CCI for 7 days was significantly increased in BeD-treated group of animals compared to the control and BGJTD-treated groups. Compositional comparison of BeD revealed that the neurite outgrowth was facilitated by the treatments of Panax ginseng and Paeonia lactiflora. Together, these data suggest that BeD induces unique molecular response at the injury site and may trigger retrograde signaling into the neuronal cell body to modulate pain responses.

Facilitating effects of Buyang Huanwu decoction on axonal regeneration after peripheral nerve transection.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Asian medicine, Buyang Huanwu decoction (BYHWD) has been used for the treatment of cardiovascular and neurological disorders. Recent experimental studies have begun to provide evidence on the protective effects of BYHWD on injured peripheral nerves. AIM OF THE STUDY: To examine whether BYHWD was effective in inducing axonal regeneration after peripheral nerve transection, and if so, how it acted on the nerve. MATERIALS AND METHODS: The sciatic nerve in rats was transected and resutured 0, 1, or 4 weeks later. BYHWD was orally administered daily into the animals with nerve transection and coaptation (NTC). Axonal regeneration was measured by immunofluorescence staining of NF-200 and superior cervical ganglion 10 (SCG10) and by retrograde tracing method. Changes of protein levels in the sciatic nerve were analyzed by western blot analysis. Effects of BYHWD and its constituents on neurite outgrowth were analyzed in cultured dorsal root ganglion (DRG) neurons. Hot plate and treadmill training tests were performed to assess the levels of functional recovery after nerve injury. RESULTS: The rate of axonal regeneration was attenuated by delayed coaptation after transection, but improved by BYHWD treatment. Levels of phospho-Erk1/2 and Cdc2 phosphorylation of vimentin, measured as indicators of the activation of regenerating axons and supportive Schwann cells, were increased in the sciatic nerve of NTC animals, and their distribution in the proximal and distal nerves were affected by BYHWD treatment. Treatment of BYHWD during the period of chronic denervation significantly increased axonal regeneration when analyzed by immunofluorescence staining and retrograde tracing methods. Neurite outgrowth of DRG neurons cocultured with Schwann cells from the chronically transected sciatic nerves was enhanced by BYHWD treatment. Radix Paeoniae Rubra induced neurite outgrowth most efficiently among all herbal constituents of BYHWD. Finally, hot plate and treadmill training tests demonstrated that BYHWD administration significantly improved the sensorimotor nerve function in NTC animals. CONCLUSIONS: Our data suggest that BYHWD treatment may contribute to the timely interaction between regenerating axons and distal Schwann cells in the transected nerve and facilitate axonal regeneration.

Modulation of hippocampal neuronal activity by So-ochim-tang-gamibang in mice subjected to chronic restraint stress.

BACKGROUND: So-ochim-tang-gamibang (SOCG) is a decoction formula which has been used to improve mental activity in traditional Korean medicine. The present study was performed to evaluate whether the treatment of SOCG was involved in activating hippocampal neurons in mice which were subjected to chronic restraint stress (CRS). METHODS: Mice were subjected to CRS for 2 weeks to induce depressive-like behaviors. SOCG was orally administered for the same period. mRNA expression in the hippocampus was analyzed by RT-PCR. Levels of serotonin receptor 5-HT1AR in the hippocampus were determined by western blotting and by immunofluorescence staining in coronal brain sections. Cultured neurons were prepared from the dorsal root ganglia (DRG) in mice to examine the effects of CRS and SOCG treatment on neurite outgrowth. Depressive-like behaviors of experimental animals were measured by open field test (OFT) and forced swimming test (FST). RESULTS: mRNA levels of serotonin 1A and 1B receptors (5-HT1AR and 5-HT1BR) were decreased in the hippocampus of CRS animals and increased by SOCG treatment. Signals of 5-HT1AR protein in CA3 pyramidal cells were decreased by CRS but elevated back to levels in control animals after SOCG treatment. Phospho-Erk1/2 protein in CA3 cells showed similar pattern of changes as in 5-HT1AR, suggesting coordinated regulation after SOCG treatment in CRS animals. Axonal growth-associated protein GAP-43 levels were also decreased by CRS and then increased by SOCG treatment. In vivo administration of SOCG improved neurite outgrowth of primary DRG neurons from CRS animals and also increased 5-HT1AR protein signals. Behavioral tests of open field and forced swimming showed that immobility time periods were significantly decreased by SOCG treatment. CONCLUSIONS: Our data suggest that SOCG treatment may increase synaptic responsiveness to serotonergic neuronal inputs by upregulating 5-HT1AR in the hippocampal neurons.

Protective Effects of Bogijetong Decoction and Its Selected Formula on Neuropathic Insults in Streptozotocin-Induced Diabetic Animals.

Bogijetong decoction (BGJTD) is a mixture of herbal formulation which is used in the traditional Korean medicine for the treatment of neuropathic pain caused by diabetes. Here, we investigated the regulatory effects of BGJTD and its reconstituted decoction subgroups on the neuropathic responses in streptozotocin- (STZ-) induced diabetic animals. Be decoction (BeD) was formulated by selecting individual herbal components that induced neurite outgrowth most efficiently in each subgroup. BeD induced the neurite outgrowth in DRG neurons most efficiently among decoction subgroups and downregulated the production of TNF-α from the sciatic nerves in STZ-diabetic animals. While the levels of phospho-Erk1/2 were elevated in the sciatic nerves of STZ-diabetic animals by BGJTD and BeD treatments, p38 level was downregulated by BGJTD and BeD. A single herbal component of BeD induced neurite outgrowth comparable to BeD and was involved in the regulation of Erk1/2 activation and TNF-α production in DRG neurons. Oral administration of BGJTD and BeD in STZ-diabetic animals reduced the latency time responding to thermal stimulation. Our results suggest that the reconstituted formulation is as effective as conventional BGJTD in inducing biochemical and behavioral recoveries from the neuropathy in peripheral nerves and thus the experimental reductionism may be applied to develop the methodology for compositional analysis of herbal decoctions.

Bogijetong decoction and its active herbal components protect the peripheral nerve from damage caused by taxol or nerve crush.

BACKGROUND: Bogijetong decoction (BGJTD) is a herbal drug formulation used in the traditional Asian medicine to treat neuropathic insults associated with diabetes and anticancer therapy. To understand the biological basis of BGJTD on protective effects against neuropathy, we investigated physiological and biochemical responses of the sciatic nerves deranged by taxol injection or crush injury in the rats. METHODS: Dissociated Schwann cells and neurons were prepared from the sciatic nerve and dorsal root ganglia (DRG) respectively and were treated with taxol and BGJTD. The sciatic nerve in the rat was injected with taxol or given crush injury. Animals were then administered orally with BGJTD. Effects of BGJTD treatment on cultured cells and in vivo sciatic nerves and DRG tissues were examined by immunofluorescence staining and western blot analysis. Sciatic nerve regeneration was assessed by histological observation using retrograde tracing technique and by behavioral hot plate test. Eighteen different herbal components of BGJTD were divided into 4 subgroups and were used to select herbal drugs that enhanced neurite outgrowth in cultured neurons. RESULTS: Morphological abnormalities in the sciatic nerve axons and DRG tissue caused by taxol injection were largely improved by BGJTD treatment. BGJTD treatment enhanced neurite outgrowth in cultured DRG neurons and improved Schwann cell survival. Phospho-Erk1/2 levels were elevated by BGJTD administration in the injured- or taxol-injected sciatic nerves. Vimentin phosphorylation catalyzed by cell division cycle 2 (Cdc2) kinase was induced from Schwann cells in the sciatic nerves after taxol injection and crush injury, and phospho-vimentin levels were further upregulated by BGJTD treatment. Retrograde tracing of DiI-labeled DRG sensory neurons revealed growth-promoting activity of BGJTD on axonal regeneration. A drug group (Be) composed of 4 active herbal components which were selected by neurite growth-enhancing activity was as effective as BGJDT for the recovery of thermal sensitivity of the hind paws which had been suppressed by taxol administration. CONCLUSIONS: These data suggest that BGJTD and its active herbal components may protects the peripheral nerve from damage caused by taxol injection and nerve crush.

Enhanced axonal regeneration of the injured sciatic nerve by administration of Buyang Huanwu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu decoction (BYHWD) has been used in the traditional Chinese medicine for the treatment of cardiovascular and neurological symptoms, and recent experimental studies have begun to provide evidence showing its protective effects on neural cells. Yet, its function for the regenerative responses of axons in the peripheral nerve after injury is not known. AIM OF THE STUDY: The primary objective of the present study was to explore that BYHWD is involved in growth-promoting activity of the peripheral nerve axons after injury. We further examined whether the effect of BYHWD exerted directly on regrowing axons or Schwann cells. MATERIALS AND METHODS: Sciatic nerves in rats were given crush injury, and BYHWD was injected by oral administration. Sciatic nerves or DRG tissues were prepared for immunofluorescence staining and western blot analysis. Levels of axonal regeneration were quantified by retrograde tracing technique. Cultured DRG sensory neurons and Schwann cells were prepared from rats and used to examine the effects of BYHWD on the neurite outgrowth. Behavioral analysis on functional recovery after nerve injury was assessed in mice by pin prick test, adhesive removal test, and toe-spreading reflex. RESULTS: Immunofluorescence and retrograde tracing analyses showed that the distal extension of the sciatic nerve axons was significantly improved by BYHWD treatment. Levels of axonal growth-associated protein GAP-43 were upregulated by BYHWD treatment in the sciatic nerve after injury and in the neurites of cultured DRG neurons. In vivo administration of BYHWD in rats upregulated the induction level of cell division cycle 2 (Cdc2) and its phosphorylation of vimentin in Schwann cells from injured sciatic nerve. Coculture of DRG neurons with Schwann cells prepared from preinjured sciatic nerves in animals administered with BYHWD led to the enhancement in neurite outgrowth. Behavioral tests in mice given sciatic nerve injury showed a significant improvement in sensorimotor activity by BYHWD administration. CONCLUSIONS: Our results suggest that BYHWD administration into animals given sciatic nerve injury facilitates axonal regeneration by acting on both the axons undergoing regeneration and neighboring Schwann cells and improves functional recovery.

Effects of Smart-Tablet-Based Neurofeedback Training on Cognitive Function in Children with Attention Problems.

We sought to determine whether smart-tablet-based neurofeedback could improve executive function-including attention, working memory, and self-regulation-in children with attention problems. Forty children (10-12 years old) with attention problems, as determined by ratings on the Conners Parent Rating Scale, were assigned to either a neurofeedback group that received 16 sessions or a control group. A comprehensive test battery that assessed general intelligence, visual and auditory attention, attentional shifting, response inhibition and behavior rating scales were administered to both groups before neurofeedback training. Several neuropsychological tests were conducted at posttraining and follow-up assessment. Scores on several neuropsychological tests and parent behavior rating scales showed significant improvement in the training group but not in the controls. The improvements remained through the follow-up assessment. This study suggests that the smart-tablet-based neurofeedback training program might improve cognitive function in children with attention problems.

Bimetallic Pt-Au Nanocatalysts on ZnO/Al2O3/Monolith for Air Pollution Control.

The catalytic activity of a monolithic catalyst with nanosized Pt and Au particles on ZnO/Al2O3 (Pt-Au/ZnO/Al2O3/M) prepared by a wash-coat method was examined, specifically for toluene oxidation. Scanning electron microscopy image showed clearly the formation of a ZnO/Al2O3 layer on the monolith. Nanosized Pt-Au particles on ZnO/Al2O3/M with different sizes could be found in the Pt-Au/ZnO/Al2O3/M catalyst. The conversion of toluene decreased with increasing toluene concentration and was also largely affected by the feed flow rate. The Pt-Au/ZnO/Al2O3/M catalysts prepared in this work have almost the same activity (molecules of toluene per second) compared with a powder Pt-Au/ZnO/Al2O3 catalyst with the same loadings of Pt and Au components; thus this catalyst could be used in controlling air pollution with very low concentrations and high flow rate.

Managing tuberous sclerosis in the Asia-Pacific region: refining practice and the role of targeted therapy.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder, with heterogeneous manifestations that pose major diagnostic and management challenges and incur considerable chronic disease burden on patients, their caregivers and healthcare systems. This survey of clinical practice in the Asia-Pacific region highlights priorities for improving TSC management in the region. The prevalence of TSC in non-Caucasians is uncertain and more data are needed to assess its impact and health-economic burden. There are unmet needs for access to genetic testing and earlier diagnosis and intervention. TSC management is multidisciplinary and largely based on experience, backed by international guidelines; however, physicians in the Asia-Pacific region feel isolated and lack local or regional guidance and support structures to implement best-practice. Raising awareness of TSC and increasing trans-regional collaboration are particular priorities. Understanding of TSC pathophysiology has enabled the development of targeted therapies. Encouraging data indicate that mammalian target of rapamycin (mTOR) inhibitors can ameliorate TSC-related lesions and may potentially change the treatment paradigm. Ultimately, improving outcomes for TSC patients in the region requires greater collaboration and a holistic, patient-focused, continuum of care that is maintained through the transition from pediatric to adult care.

Effect of nanosized gold particle addition to supported metal oxide catalyst in methanol oxidation.

Gold has rarely been utilized as a catalytic component because of its poor affinity to chemical species. It is however known that nanosized gold particles promote the dissociation of oxygen or hydrogen. In this study, alumina-supported metal oxide catalysts were prepared by impregnation method and applied to methanol oxidation. The dispersion form and size of the gold particles were observed by transmission electron microscopy (TEM). In the results, the maximum catalytic activity was obtained over the ZnO/Al2O3 catalyst, and the optimum loading was 4 wt%. Furthermore, nano-sized gold particles at various loadings were added to ZnO/Al2O3 catalyst by deposition method. The gold particles on Au/ZnO/Al2O3 catalyst were well dispersed and the catalyst activity was remarkably increased compared to ZnO/Al2O3 catalyst. The role of gold particles in the increased catalytic activity is discussed and a possible mechanism is presented.

Complete chloroplast genome sequences from Korean ginseng (Panax schinseng Nees) and comparative analysis of sequence evolution among 17 vascular plants.

The nucleotide sequence of Korean ginseng (Panax schinseng Nees) chloroplast genome has been completed (AY582139). The circular double-stranded DNA, which consists of 156,318 bp, contains a pair of inverted repeat regions (IRa and IRb) with 26,071 bp each, which are separated by small and large single copy regions of 86,106 bp and 18,070 bp, respectively. The inverted repeat region is further extended into a large single copy region which includes the 5' parts of the rpsl9 gene. Four short inversions associated with short palindromic sequences that form stem-loop structures were also observed in the chloroplast genome of P. schinseng compared to that of Nicotiana tabacum. The genome content and the relative positions of 114 genes (75 peptide-encoding genes, 30 tRNA genes, 4 rRNA genes, and 5 conserved open reading frames [ycfs]), however, are identical with the chloroplast DNA of N. tabacum. Sixteen genes contain one intron while two genes have two introns. Of these introns, only one (trnL-UAA) belongs to the self-splicing group I; all remaining introns have the characteristics of six domains belonging to group II. Eighteen simple sequence repeats have been identified from the chloroplast genome of Korean ginseng. Several of these SSR loci show infra-specific variations. A detailed comparison of 17 known completed chloroplast genomes from the vascular plants allowed the identification of evolutionary modes of coding segments and intron sequences, as well as the evaluation of the phylogenetic utilities of chloroplast genes. Furthermore, through the detailed comparisons of several chloroplast genomes, evolutionary hotspots predominated by the inversion end points, indel mutation events, and high frequencies of base substitutions were identified. Large-sized indels were often associated with direct repeats at the end of the sequences facilitating intra-molecular recombination.