Gait Disturbance Improvement and Cerebral Cortex Rearrangement by Acupuncture in Parkinson's Disease: A Pilot Assessor-Blinded, Randomized, Controlled, Parallel-Group Trial.

BACKGROUND: Parkinson's disease (PD) leads to impaired mobility and limited independence. OBJECTIVE: We investigated the effects of acupuncture on gait disturbance and analyzed hemodynamic changes caused by acupuncture in the cerebral cortex of patients with PD. METHODS: Participants (n = 26) with gait disturbance due to PD were randomly assigned to the intervention (acupuncture twice a week for 4 weeks + conventional therapy) or control (conventional therapy) groups. We analyzed gait parameters using the GAITRite system and hemodynamic responses in the cerebral cortices using functional near-infrared spectroscopy, Unified Parkinson's Disease Rating Scale (UPDRS) scores, neurotransmitter levels, as well as the immediate effects of acupuncture in patients with PD. RESULTS: The participants tended to walk with hypometric gait (high cadence, short steps) overground. After acupuncture treatment, those in the intervention group showed a significant reduction in cadence and the UPDRS scores involving "walking and balance" compared with those in the control group (P = .004 and P = .020, respectively); the stride, swing, and single support times were significantly increased (P = .006, P = .001, and P = .001, respectively). Oxyhemoglobin levels in the intervention group while walking on a treadmill were significantly increased in the prefrontal and supplementary motor areas. The oxyhemoglobin levels in the prefrontal cortex and swing time revealed significant positive correlations. CONCLUSIONS: Our findings indicated that acupuncture tended to improve hypometric gait and rearranged activation of the cerebral cortex. Thus, acupuncture may be a useful complementary treatment for gait disturbance, including hypometric gait, in patients with PD. Trial Registration Number. Clinical Research Information Service (KCT0002603), https://cris.nih.go.kr/cris/index.jsp.

7­MEGA™ 500 regulates the expression of COX­2, MMP­3 and type 1 procollagen in UVB­irradiated human keratinocytes and dermal fibroblasts.

AlaskOmega® Omega 7 500, also known as Omega­7 fatty acid or 7­MEGA™, is a highly concentrated palmitoleic acid (C16:1). Little is known about how 7­MEGA regulates skin inflammation and wrinkle formation in cultured skin cells. The present study aimed to investigate the effects of 7­MEGA on the expression of cyclooxygenase­2 (COX­2), matrix metallopeptidase (MMP)­1/3 and type 1 procollagen, which are markers of skin inflammation and wrinkle formation, in ultraviolet B (UVB)­irradiated human dermal fibroblasts (HDFs) and keratinocytes (HaCaT). No toxicity was observed upon treatment of HDFs and HaCaT cells with 0.5­2.5 µl/ml 7­MEGA. The exposure of HaCaT cells to 10 mJ/cm2 UVB for 6 h resulted in increased protein and/or mRNA expression of COX­2 and MMP­3. Treatment of HaCaT cells with 2.5 µl/ml 7­MEGA suppressed the UVB­induced expression of COX­2 and MMP­3 in these cells. In addition, treatment with 2.5 µl/ml 7­MEGA attenuated the UVB­induced expression and phosphorylation levels of c­Fos and c­Jun, two components of the activator protein­1 (AP­1) transcription factor, in HaCaT cells. Exposure of HDFs to 60 mJ/cm2 UVB for 6 h significantly decreased the expression of type 1 procollagen protein, whereas treatment with 2.5 µl/ml 7­MEGA partially reversed the effects of UVB on the expression of type 1 procollagen protein. These results demonstrated for the first time that 7­MEGA regulated the expression of COX­2, MMP­3 and type 1 procollagen in UVB­irradiated skin cells. The present study suggested that 7­MEGA may serve as a novel agent against UVB­induced skin inflammation and damage.

Beta wave enhancement neurofeedback improves cognitive functions in patients with mild cognitive impairment: A preliminary pilot study.

BACKGROUND: Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI. METHODS: This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC-16 sessions for 8 weeks-with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores. RESULTS: After completing the training, patients' cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training. CONCLUSION: We suggest that patients' cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0003433).

Inhibitory effects of Euphorbia supina on Propionibacterium acnes-induced skin inflammation in vitro and in vivo.

BACKGROUND: Euphorbia supina (ES) plant has been used as treatment for inflammatory conditions. The antibacterial effect and the anti-inflammatory mechanism of ES for Propionibacterium (P.) acnes-induced inflammation in THP-1 cells and acne animal model remain unclear. Therefore, the objective of the present study was to determine the antibacterial and anti-inflammatory activities of ES against P. acnes, the etiologic agent of skin inflammation. METHOD: The antibacterial activities of ES were tested with disc diffusion and broth dilution methods. Cytotoxicity of ES at different doses was evaluated by the MTT assay. THP-1 cells were stimulated by heat-killed P. acnes in the presence of ES. The pro-inflammatory cytokines and mRNA levels were measured by ELISA and real-time-PCR. MAPK expression was analyzed by Western blot. The living P. acnes was intradermally injected into the ear of BLBC/c mice. Subsequently, chemical composition of ES was analyzed by liquids chromatography-mass spectrometry (LC-MS). RESULT: ES had stronger antibacterial activity against P. acnes and inhibitory activity on lipase. ES had no significant cytotoxicity on THP-1 cells. ES suppressed the mRNA levels and production of IL-8, TNF-a, IL-1ß in vitro. ES inhibited the expression levels of pro-inflammatory cytokines and the MAPK signaling pathway. Ear thickness and inflammatory cells were markedly reduced by ES treatment. Protocatechuic acid, gallic acid, quercetin, and kaempferol were detected by LC-MS analysis in ES. CONCLUSIONS: Our results demonstrate antibacterial and anti-inflammatory activities of ES extract against P. acnes. It is suggested that ES extract might be used to treatment anti-inflammatory skin disease.

Antioxidant Activity of Royal Jelly Hydrolysates Obtained by Enzymatic Treatment.

Recently, research on the processing of raw functional materials with the aim of improving various physiological activities has been conducted. In this study, we investigated the antioxidant activity of royal jelly (RJ) hydrolysates obtained from three commercial proteases. Enzyme-treated royal jelly (ERJ), in which the RJ hydrolysates were converted into easy-to-absorb shorter chain monomers through the removal of two known allergen proteins, showed no difference in the content of (E)-10-hydroxydec-2-enoicacid (10-HDA) or the freshness parameter and showed a significant increase in total free amino acid content. The antioxidant activity of ERJ was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and chemical assays. The ERJ showed about 80% DPPH-radical scavenging activity at same concentration of ascorbic acid. The antioxidant effect of ERJ was confirmed to be due to reduction of intracellular reactive oxidative species (ROS) and nitric oxide (NO) production in LPS-treated macrophages. Moreover, ERJ significantly increased the activity of the antioxidant enzyme superoxide dismutase (SOD) and the level of the antioxidant glutathione (GSH) in a dose-dependent manner. Interestingly, these antioxidant activities of ERJ were stronger than those of non-treated RJ. These findings indicate that ERJ has high potential as an antioxidant agent for use in human and animal diets.

Chrysanthemum indicum L. ethanol extract reduces high-fat diet-induced obesity in mice.

The present study was undertaken to investigate the mechanism behind the anti-obesity effect of the 50% ethanol extract of Chrysanthemum indicum L. flowers (CIEE) in a mouse model of high-fat diet (HFD)-induced obesity. Male C57BL/6J mice (six mice in each group) were administered CIEE (8, 40 and 200 mg/kg) for 6 weeks while being fed with a HFD. Garcinia cambogia (GC) was used as the positive control and was administered in the same manner as CIEE. Results demonstrated that oral administration of CIEE significantly reduced body weight, epididymal white adipose tissue (EWAT), liver weight and serum levels of total cholesterol and triglyceride (P<0.05). In addition, CIEE reduced serum leptin and increased adiponectin levels. CIEE significantly downregulated peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein-α and fatty acid synthase expression levels in EWAT, and upregulated the protein expression of PPARα in liver tissue of HFD-fed obese mice (P<0.05). These results suggested that Chrysanthemum indicum L. flowers may be a potentially effective therapeutic agent for obesity and its associated complications.

Effects of 7-MEGATM 500 on Oxidative Stress, Inflammation, and Skin Regeneration in H2O2-Treated Skin Cells.

Environmental stimuli can lead to the excessive accumulation of reactive oxygen species (ROS), which is one of the risk factors for premature skin aging. Here, we investigated the protective effects of 7-MEGATM 500 (50% palmitoleic acid, 7-MEGA) against oxidative stress-induced cellular damage and its underlying therapeutic mechanisms in the HaCaT human skin keratinocyte cell line (HaCaT cells). Our results showed that treatment with 7-MEGA prior to hydrogen peroxide (H2O2)-induced damage significantly increased the viability of HaCaT cells. 7-MEGA effectively attenuated generation of H2O2-induced reactive oxygen species (ROS), and inhibited H2O2-induced inflammatory factors, such as prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). In addition, cells treated with 7-MEGA exhibited significantly decreased expression of matrix metalloproteinase-1 (MMP-1) and increased expression of procollagen type 1 (PCOL1) and Elastin against oxidative stress by H2O2. Interestingly, these protective activities of 7-MEGA were similar in scope and of a higher magnitude than those seen with 98.5% palmitoleic acid (PA) obtained from Sigma when given at the same concentration (100 nL/mL). According to our data, 7-MEGA is able to protect HaCaT cells from H2O2-induced damage through inhibiting cellular oxidative stress and inflammation. Moreover, 7-MEGA may affect skin elasticity maintenance and improve skin wrinkles. These findings indicate that 7-MEGA may be useful as a food supplement for skin health.

Chrysanthemum indicum Inhibits Adipogenesis and Activates the AMPK Pathway in High-Fat-Diet-Induced Obese Mice.

Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.

Anti-inflammatory effect of Euphorbia supina extract in dextran sulfate sodium-induced colitis mice.

The aim of this study is to examine the anti-inflammatory effect of Euphorbia supina (ES) ethanol extract in dextran sulfate sodium (DSS)-induced experimental colitis model. ES was per orally administered at different doses of 4 or 20 mg/kg body weight with 5% DSS in drinking water for 7 days. Twenty mg/kg of ES administration regulated body weight decrease, recovered colon length shortening, and increased disease activity index score and myeloperoxidase level in DSS-induced colitis. Histological features showed that 20 mg/kg of ES administration suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, ES suppressed the expressions of COX-2, iNOS, NF-kB, IkBα, pIkBα in colon tissue. These findings demonstrated a possible effect of amelioration of ulcerative colitis and could be clinically applied.

Triticum aestivum sprout-derived polysaccharide exerts hepatoprotective effects against ethanol-induced liver damage by enhancing the antioxidant system in mice.

Triticum aestivum sprout-derived polysaccharide (TASP) has anti-diabetic properties, but no information is available in regards to its protective effect against ethanol-induced hepatic injury. This study aimed to investigate the mechanism behind the protective role of TASP against ethanol-induced liver injury in vivo. Male C57BL/6 mice were administered ethanol with or without TASP for 10 consecutive days by oral gavage. Silymarin was administered in the same manner as a positive control. TASP reduced ethanol-induced hepatic lipid accumulation and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. TASP also prevented glutathione (GSH) depletion and increased the superoxide dismutase (SOD) in liver tissue. In addition, TASP significantly inhibited ethanol-induced cytochrome P450 2E1 (CYP2E1) activation, and upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and downregulated NADPH oxidase genes in ethanol fed mice. Furthermore, the upregulation of Nrf2 was found to be regulated by a phosphatidylinositol 3-kinase (PI3K)/Akt pathway. TASP also attenuated hepatic injury by modulation of caspase-3 and apoptosis-associated mitochondrial proteins including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) in liver tissues of mice. The study demonstrated that TASP treatment protects against ethanol-induced hepatic injury via multiple pathways by inhibiting steatosis and improving antioxidant marker levels during hepatic injury. Such properties provide a basis for therapeutic agents against alcohol-induced liver injury.

Sterols from Hericium erinaceum and their inhibition of TNF-α and NO production in lipopolysaccharide-induced RAW 264.7 cells.

Erinarols G-J and 10 known ergostane-type sterols were isolated from a methanol extract of the dried fruiting bodies of Hericium erinaceum. Their chemical structures were elucidated using extensive spectroscopic analyses including 1D and 2D NMR experiments and HR-ESI-MS analysis, as well as through comparison with previously reported data. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of tumor necrosis factor α (TNF-α) and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells. The results showed that erinarols H and J, as well as 2 of the ergostane-type sterols exhibited inhibitory activity against TNF-α secretion, with inhibition values ranging from 33.7% to 43.3% at 10 µM. Erinarols J and three ergostane-type sterols exhibited significant inhibitory effects against NO production, with inhibition values ranging from 38.4% to 71.5% at 10 µM.

Anti-inflammatory components of Chrysanthemum indicum flowers.

One new octulosonic acid derivative, chrysannol A (1), along with 17 known compounds (2-18), were isolated from Chrysanthemum indicum flowers. Their structures were determined from 1D NMR, 2D NMR, HR-ESI-MS spectral data, and comparisons with previous reports. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compound 8 showed the highest inhibition of NO production of 46.09% at a concentration of 10.0µM. Compounds 7, 10, 11, and 16 inhibited TNF-α secretion at all concentration tested (0.4, 2.0, and 10.0µM), with inhibition values ranging from 22.27% to 33.13%. In addition, compound 8 and 9 decrease COX-2 and iNOS protein on Western blot analysis in dose dependent manner.

A new phenolic component from Triticum aestivum sprouts and its effects on LPS-stimulated production of nitric oxide and TNF-α in RAW 264.7 cells.

An unusual new phenolic component, triticumoside (1), and eight known compounds, isoorientin (2), isoscoparin (3), (2R)-2-O-ß-D-glucopyranosyloxy-4,7-dimethoxy-2H-1,4-benzoxazin-3(4H)-one (4), adenosine (5), ß-sitosterol (6), daucosterol (7), 6'-O-linolenoyl daucosterol (8), α-tocopherol (9), were isolated fromTriticum aestivum sprouts. The hybrid structure of 1, which is a hybrid between a flavone and a polyoxygenated benzene, is rarely found in natural sources. In addition, the effects of these compounds on LPS-induced NO and TNF-α production in RAW 264.7 cells were evaluated. At a concentration of 2.0 µM, compounds 2-4 significantly inhibited the production of both NO and TNF-α. Compound 1 exhibited inhibitory activity on the secretion of TNF-α at concentrations as low as 2.0 µM, but it did not reduce NO levels at any of the tested concentrations.

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3-26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10-21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC50 values as low as 18.05±1.17, 18.64±1.83, and 17.23±0.84 µM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3-6, 8, 18, 20-23, and 25-26 inhibited the production of both NO and TNF-α, with IC50 values ranging from 11.1±0.9 to 45.3±1.6 µM and 14.4±0.5 to 44.5±1.2 µM, respectively.

Triterpenoid saponins of Pulsatilla koreana root have inhibition effects of tumor necrosis factor-α secretion in lipopolysaccharide-induced RAW264.7 cells.

In the present study, a new oleanane-type triterpenoid saponin, pulsatilloside F (1), along with 21 known compounds (2-22), were isolated from the root of Pulsatilla koreana. Their chemical structures were elucidated by mass, (1)H-, (13)C-NMR, correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond connectivity (HMBC) spectroscopy. Anti-inflammatory effects of the compounds were evaluated in terms of inhibitory of tumor necrosis factor α (TNF-α) secretion in the lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cell line. Compounds 19 and 20 exhibited particularly inhibitory effects with respective IC50 values of 0.32 and 0.65 µm. Compounds 1-4, 7 and 10-13 exhibited inhibitory effects with inhibition rates up to 41.55-73.76% at a concentration of 5 µm, respectively.

Inhibitory effect on TNF-α-induced IL-8 secretion in HT-29 cell line by glyceroglycolipids from the leaves of Ficus microcarpa.

Bioassay-guided fractionation based on the anti-inflammatory activity of a methanol extract of Ficus microcarpa leaves led to the isolation of seven galactolipids: 2(S)-3-O-octadeca-9Z,12Z,15Z-trienoylglyceryl-O-ß-D-galactopyranoside (1), (2S)-2,3-O-dioctadeca-9Z,12Z,15Z-trienoylglyceryl-O-ß-D-galactopyranoside (2), (2S)-2,3-O-dioctadeca-9Z,12Z-dienoylglyceryl-O-ß-D-galactopyranoside (3), (2S)-3-O-octadeca-9Z,12Z,15Z-trienoylglyceryl-6'-O-(α-D-galactopyranosyl)-ß-D-galactopyranoside (4), (2S)-2,3-O-dioctadeca-9Z,12Z,15Z-trienoylglyceryl-6'-O-(α-D-galactopyranosyl)-ß-D-galactopyranoside (5), gingerglycolipid B (6), and (2S)-2,3-O-dioctadeca-9Z,12Z-dienoylglyceryl-6'-O-(α-D-galactopyranosyl)-ß-D-galactopyranoside (7). Their chemical structures were elucidated by mass, 1D-, and 2D-NMR spectroscopic methods as well as chemical methods. The antiinflammatory effect of these compounds on TNF-α induced IL-8 secretion in the HT-29 cell line was evaluated. All above galactolipids showed significant inhibition ranging 40% at a concentration of 50 µM. The results suggest that galactolipids from the leaves of F. microcarpa may be used as potent anti-inflammatory agents.