Tissue Concentration Analysis of Sulfur, Calcium and Oxygen in Novel Skin Primo Nodes After Acupuncture.

Over the past 5000 years, acupuncture has been practiced in Korea, China, and Japan to relieve various diseases, and it is now widely used and accepted worldwide. Although the anatomical substance and function of meridians has been actively studied, it is still not clearly defined. One of the keys to acupuncture is determining the specific anatomical location exactly on or under the skin. We discovered that the skin primo node is a new anatomical structure in the skin of rats. The present study aimed to analyze the relationship between skin primo nodes and acupoints through changes in the expression of tissue concentrations of skin primo nodes. Analysis of this skin primo node confirmed that the skin primo node after acupuncture had a significantly higher concentration of sulfur and calcium than found in normal skin. And the significant pO2 in the skin primo node was confirmed by measuring pO2 using a needle oxygen sensor. Through sulfur, calcium, and pO2 concentration values of skin primo nodes, we confirmed whether these nodes could be related to acupoint. To understand the clear structure and function of this node, it is necessary to further study through the known properties of acupoints and the function of Primo Vascular System (PVS).

Primo Vessels Inside Lymphatic Vessels Are Absent in an ALS Mouse Model.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the central nervous system. It is also a representative rare disease among degenerative diseases of the nervous system. Although many drugs for the treatment of degenerative brain diseases are being developed, they are not delivered correctly to the target due to the blood-brain barrier. The present study aimed to analyze changes in the primo vascular system (PVS) in ALS mice with symptoms and the partial oxygen pressure (pO2) in normal mice. In normal mice, we consistently observed primo vessels in lymphatic vessels (L-PVS). However, in ALS mice with symptoms, L-PVS were mostly lost, rendering them difficult to observe. The pO2 of the L-PVS in normal mice was significantly higher than that of normal dermis and lymph nodes.In conclusion, the relatively higher oxygen levels measured in the L-PVS than in normal dermis and lymph nodes suggest a role for the PVS in oxygen transport and enable a hypothesis that the L-PVS can function as a drug delivery pathway.

Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by progressive paralysis of voluntary muscles. Mecasin, the extract of modified jakyakgamchobuja-tang-a herbal preparation comprising of Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Gastrodiae, Radix Polygalae, Curcuma Root, Fructus Chaenomelis, and Rhizoma Atractylodis Japonicae-shows neuroprotective and anti-neuroinflammatory effects and alleviates the symptoms in patients with ALS. AIM OF THE STUDY: This trial aimed to evaluate the efficacy and safety of mecasin in these patients. MATERIAL AND METHODS: Patients were randomized to receive mecasin 1.6 g daily, mecasin 2.4 g daily, or placebo for 12 weeks. The primary endpoint was the Korean version of ALS Functional Rating Scale-Revised (K-ALSFRS-R) score. The secondary endpoints were muscular atrophy measurements, pulmonary function test results, creatine kinase levels, body weight, safety, and scores of the Medical Research Council (MRC) scale for muscle strength; Visual Analog Scale for pain (VAS pain); Hamilton Rating Scale for Depression; and Fatigue Severity Scale. RESULTS: Among the 30 patients randomized, 24 completed the follow-up. Significant between-group differences were detected in the primary endpoint using the omnibus F-test. The changes in the K-ALSFRS-R score between 12 weeks and baseline were -0·25, -1·32, and -2·78 in the mecasin 1.6 g, mecasin 2.4 g, and placebo groups, respectively. The difference in the K-ALSFRS-R score between the mecasin 1.6 g and placebo groups was 2·53 points (95% confidence interval [CI]: 0·61-4·45), and that between the 2.4 g and placebo groups was 1·46 points (95% CI: 0·48-3·40). However, no significant differences were detected in the secondary endpoints (MRC: dyspnea, p = 0·139; VAS pain, p = 0·916; forced vital capacity, p = 0·373). The incidence of adverse events was similar and low in all groups. CONCLUSIONS: Mecasin may retard symptomatic progression without major adverse effects. A phase IIb study to evaluate its long-term effects in ALS is ongoing.

Safety and efficacy of Jujadokseo-hwan for memory deficit (amnesia) in mild neurocognitive disorder: A protocol for randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial.

BACKGROUND: Mild neurocognitive disorder (mNCD) is one of the degenerative diseases that results in memory deficit, and can progress to dementia. The effectiveness of drug therapy for mNCD is still debatable, but treatment of this disease has important implications for postponing or preventing dementia. Jujadokseo-hwan (JDH) is a traditional herbal medicine formulation that exhibits improvement in cognitive abilities and neuroprotective effects. In this study, we will evaluate the safety and efficacy of JDH compared to placebo in mNCD patients. METHODS AND DESIGN: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. After obtaining informed consent from all participants and performing the screening process, the participants will be equally divided into an experimental group and a control group. Each participant will visit the trial center 7 times during the 12 weeks of intervention. The follow up study will be conducted 12 weeks after the intervention ends. The primary outcome is the variance in Seoul verbal learning test-elderly's version (SVLT-E) score from baseline to 12 weeks. Secondary outcomes include scores/values for the following variables: SVLT-E, Rey complex figure test, Digit span test, Korean-Boston naming test, calculation ability, controlled oral word association test, Korean-color word stroop test, digit symbol coding, Korean-trail making test-elderly's version, Korean version of mini mental state examination for dementia screening, euro-qol-5 dimension, pattern identifications tool for cognitive disorders, Korean version of Montreal cognitive assessment, Korean quality of life-Alzheimer disease, computerized tongue image analysis system, blood pressure pulse analyzer, bioelectrical impedance analyzer, wearable electroencephalogram device, functional near-infrared spectroscopy system, and cost analysis. DISCUSSION: This is the first trial evaluating the efficacy of JDH for mNCD. We expect this trial will provide strong support for wide use of JDH for mNCD and lead to further research on herbal medicine treatments for mNCD. TRIAL REGISTRATION NUMBER: KCT0003570 (Registered in Clinical Research Information Service of the Republic of Korea, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=12669).

Effectiveness of collaborative treatment using Korean and Western medicine for mild cognitive impairment or dementia: A protocol for a prospective observational exploratory study.

BACKGROUND: South Korea has a dual medical system comprising conventional Western medicine (WM) and traditional Korean medicine (KM), which has yielded both positive results (increased opportunity to choose medical care) and negative results (increased medical costs). Thus, the Ministry of Health and Welfare has been performing a pilot project to evaluate this collaborative system in the real clinical situation. As treatment of dementia requires a social approach, the Korean government aims to strengthen the role of the national health care system to reduce the burden of dementia. The aim of this study was to evaluate the clinical - and cost-effectiveness of collaborative KM and WM treatment in patients with dementia or mild cognitive impairment (MCI) in Korea. METHOD/DESIGN: In total, 180 patients with dementia or MCI will be recruited and will undergo monthly check-up for 12 weeks. Information regarding demographic characteristics, baseline disease-related data, and outcomes related to cognitive function and quality of life will be obtained. For data analysis, the patients will be classified into 2 groups using a comparative observational study design: the sole treatment group, which will receive either WM or KM alone, and the collaborative treatment group, which will receive both WM and KM. DISCUSSION: The treatment of dementia/MCI in South Korea will be studied in the real world during the pilot project. There will be no limitations on the type of treatment or the specific treatment method. Examining the clinical- and cost- effectiveness of the different methods will supply information for building an optimal medical system for the treatment of dementia/MCI. TRIAL REGISTRATION: The protocol for this study has been registered at the clinical research information service (CRIS: KCT0002868).

Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects.

The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the "closed-eye" state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS).

Acupuncture for posttraumatic stress disorder: a systematic review of randomized controlled trials and prospective clinical trials.

To evaluate the current evidence for effectiveness of acupuncture for posttraumatic stress disorder (PTSD) in the form of a systematic review, a systematic literature search was conducted in 23 electronic databases. Grey literature was also searched. The key search terms were "acupuncture" and "PTSD." No language restrictions were imposed. We included all randomized or prospective clinical trials that evaluated acupuncture and its variants against a waitlist, sham acupuncture, conventional therapy control for PTSD, or without control. Four randomized controlled trials (RCTs) and 2 uncontrolled clinical trials (UCTs) out of 136 articles in total were systematically reviewed. One high-quality RCT reported that acupuncture was superior to waitlist control and therapeutic effects of acupuncture and cognitive-behavioral therapy (CBT) were similar based on the effect sizes. One RCT showed no statistical difference between acupuncture and selective serotonin reuptake inhibitors (SSRIs). One RCT reported a favorable effect of acupoint stimulation plus CBT against CBT alone. A meta-analysis of acupuncture plus moxibustion versus SSRI favored acupuncture plus moxibustion in three outcomes. This systematic review and meta-analysis suggest that the evidence of effectiveness of acupuncture for PTSD is encouraging but not cogent. Further qualified trials are needed to confirm whether acupuncture is effective for PTSD.

Crystal structure and spontaneous magnetism of BiFeO3 powder synthesized by hydrothermal method.

Single-phase BiFeO3 powder was successively synthesized by a low-temperature hydrothermal method. Scanning electron microscopy and transmission electron microscopy results showed that BiFeO3 powder had several hundred nanometers to micrometer-sized particles with a broad size distribution. BiFeO3 powder showed weak-ferromagnetic behavior with a small magnetization value (Ms approximately 20 memu/g) at room temperature. Rietveld refinement results for the crystal structure show the displacive disorder of the Fe-site(6a); the Fe-site(6a) splits into two pairs, Fe(1) and Fe(2) displaced by 0.9 angstroms from each other and these sites are partially occupied. Hence the O-site(18b) also splits into the two partially occupied sites forming a distorted FeO6 octahedras. The weak ferromagnetism observed in the hydrothermal BFO powder is ascribed to the displacive disorder of FeO6 octahedras resulting in an incomplete counterbalance between the antiferromagnetic sublattices of the Fe-ions.

A modified preparation (LMK03) of the oriental medicine Jangwonhwan reduces Abeta(1-42) level in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease.

ETHNOPHARMACOLOGICAL RELEVANCE: The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction. Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to have a therapeutic potential to ameliorate AD-like pathology. AIM OF THE STUDY: It was investigated whether a further reduction of Jangwonhwan (LMK03-Jangwonhwan) retains the potency to suppress the AD-like pathology. MATERIALS AND METHODS: The transgenic mice of Alzheimer disease, Tg-APPswe/PS1dE9, were fed LMK03-Jangwonhwan consisting of two of the herbs, white Poria cocos (Schw.) Wolf and Angelica gigas Nakai, which could protect the AD-like pathology at 300 mg/kg/day of dose for 3 months. In vitro cell biological study, immunohistological and ELISA (enzyme-linked immunosorbent assay) analyses were used to assess its neuroprotective effects against Abeta-induced cell death, and the Abeta accumulation and plaque deposition in the brain. RESULTS: In vitro study with SH-SY5Y neuroblastoma cells showed that LMK03-Jangwonhwan could protect from cytotoxicity induced by hydrogen peroxide or oligomeric Abeta(1-42). Tg-APPswe/PS1dE9 mice were administered LMK03-Jangwonhwan at 300 mg/kg/day for 3 months from 4.5 months of age. Immunohistological and ELISA analyses showed that LMK03-Jangwonhwan partially reduced Abeta(1-42)and Abeta(1-40) levels and beta-amyloid plaque deposition in the brain of Tg-APPswe/PS1dE9 mice. However, LMK03-Jangwonhwan poorly suppressed accumulation of reactive oxidative stress in the hippocampus of Tg-APPswe/PS1dE9 mice and inefficiently improved the expression of phospho-CREB and calbindin, the cellular factors that were down-regulated in AD-like brains. CONCLUSIONS: These results suggest that LMK03-Jangwonhwan has a potency to inhibit AD-like pathology at a detectable level, but LMK03 is not likely to retain the major ability of LMK02-Jangwonhwan to modify AD pathology in several AD-related molecular parameters.

Oriental medicine Jangwonhwan reduces Abeta(1-42) level and beta-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Jangwonhwan, a boiled extract of 12 medicinal plants/mushroom including Korean red ginseng (Panax ginseng C.A. Meyer), has been prescribed for patients with cognitive dysfunction and are believed to induce brain activity enhancement, provide light sedation, and facilitate sound sleep. AIM OF THE STUDY: The present study was carried out to investigate whether Jangwonhwan has a beneficial effect on the brain of Alzheimer disease. MATERIALS AND METHODS: The transgenic mice of Alzheimer disease, Tg-APPswe/PS1dE9, were fed a modified recipe of Jangwonhwan consisting of a boiled extract of 7 herbs/mushroom (called LMK02-Jangwonhwan) at 400mg/kg/day of dose for 3 months from 4.5 months of age. Immunohistological and ELISA analyses were used to assess the Abeta accumulation and plaque deposition in the brain. Other in vitro and in vivo works were performed to understand the underlying mechanism. RESULTS: LMK02-Jangwonhwan notably reduced Abeta(1-42) and Abeta(1-40) levels, concomitantly with a reduction of plaque deposition, in the brain of Tg-APPswe/PS1dE9 mice. LMK02-Jangwonhwan partially suppressed oxidative stress accumulation, and prevented the down-regulation of phospho-CREB and calbindin typically seen in the hippocampus of AD-like brains. In vitro study with SH-SY5Y neuroblastoma cells showed that LMK02-Jangwonhwan inhibited oxidative stress and Abeta-induced neurotoxicity. CONCLUSION: The present study suggests that LMK02-Jangwonhwan confers a therapeutic potential to ameliorate AD-like pathology in the brain of Tg-APPswe/PS1dE9 mice.

Poria cocos water extract (PCW) protects PC12 neuronal cells from beta-amyloid-induced cell death through antioxidant and antiapoptotic functions.

Beta-amyloid (Abeta)-induced neurotoxicity is considered to be mediated through the formation of reactive oxygen species (ROS). In this study, the protective effects of Poria cocos water extract (PCW) against Abeta1-42-induced cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta1-42 (20 microM) for 48h resulted in neuronal cell death, whereas pretreatment with PCW at the concentration range of 5-125 microg/ml reduced Abeta1-42-induced cell death. In addition, PC12 cells treated with Abeta1-42 exhibited increased accumulation of intracellular oxidative damages and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). However, PCW attenuated Abeta1-42-induced cytotoxicity, apoptotic features, and accumulation of intracellular oxidative damage. Moreover, PCW (5 to 125 microg/ml) decreased expression of apoptotic protein Bax and activity of caspase-3, but enhanced expression of anti-apoptotic protein Bcl-2. These results suggest that PCW may protect cells through suppressing the oxidative stress and the apoptosis induced by Abeta1-42, implying that PCW may be potential natural agents for Alzheimer's diseases.

Neuroprotective effect of some plant extracts in cultured CT105-induced PC12 cells.

Carboxyl-terminal fragments of APP (CT) have been found in plaques, microvessels and the neurofibrillary tangles in the brains of AD patients. These carboxyl-terminal fragments, which contain the complete Abeta sequence, appear to be toxic to neurons in culture cells. However, the possible role of other cleaved products of APP is less clear. We showed that a recombinant carboxy-terminal 105 amino acid fragment (CT105) of APP induced strong neurotoxicity in PC12 cells. We prepared alcoholic extract from Oriental herbal plants and screened their protective effects against CT105-induced cell death in PC12 cells after the treatment of these extracts. Of the 10 kinds of plant extracts, 12 kinds of extracts had considerable protective effects against CT105-induced cell death, especially, Uncariae Ramulus et Uncus (UREU), Gastrodia elata (GAE), Evodia officinalis (EO) and Panax ginseng (PAG) showed the most protective effect at the concentration of 50 microg/ml. BuOH extract of UREU and GAE possessed the strongest protective effects against neurotoxicity of CT105-induced PC12 cells and showed inhibitory effect with IC50 values of 4.8 and 8.3 microg/ml, respectively. These plants are promising candidates of neuroprotective effects and would be useful for the treatment of the neuronal degenerative diseases such as Alzheimer's diseases.

SunghyangJungki-San Ga Pogongyoung inhibits IL-1 mediated tumour necrosis factor-alpha secretion in astrocytes.

Astrocytes play an important role in initiating and modulating inflammatory responses within the central nervous system (CNS). Extensive studies in rodents have shown that substance P induces inflammatory cytokine production in astrocytes. In this study we have examined whether an aqueous extract of SunghyangJungki-San Ga Pogongyoung (SSGP) inhibits the secretion of TNF-alpha from primary cultures of rat astrocytes. SSGP (10-1,000 microg/mL) significantly inhibited the TNF-alpha secretion by astrocytes stimulated with lipopolysaccharide (LPS) and substance P (SP). Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by SSGP. Treatment with SSGP (10-1,000 microg/mL) to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. Moreover, the secretion of TNF-alpha by LPS and SP in astrocytes was progressively inhibited with an increasing amount of IL-1 neutralizing antibody. Our results suggest that SSGP may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that SSGP has an antiinflammatory activity in the CNS.