Magnolia kobus Extract Suppresses Porphyromonas gingivalis LPS-Induced Proinflammatory Cytokine and MMP Expression in HGF-1 Cells and Regulates Osteoclastogenesis in RANKL-Stimulated RAW264.7 Cells.

Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis.

Spiraea prunifolia leaves extract inhibits adipogenesis and lipogenesis by promoting ß-oxidation in high fat diet-induced obese mice.

Spiraea prunifolia has been used in Korean traditional medicine to treat malaria, fever, and emetic conditions. Previous investigation reported that several parts of Spiraea prunifolia show various functional effects. However, the effect of Spiraea prunifolia leaves extract (SPE) on anti-obesity remains unclear. Therefore, we used a high-fat diet (HFD)-induced obese mouse model in this study to investigate the effects of SPE on adipogenesis, lipogenesis, and ß-oxidation. Oral administration of SPE in HFD-induced obese mice considerably reduced body weight, serum levels such as total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, adipose tissue weight, and adipocyte cell size. Moreover, SPE significantly decreased protein expression levels of adipogenesis and lipogenesis related genes such as CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte protein 2, acetyl-CoA carboxylase, and fatty acid synthase in epididymal adipose tissues. SPE treatment induced the protein expression of carnitine palmitoyl transferase-1, which might have promoted phosphorylated AMP-activated protein kinase-medicated ß-oxidation. The present study reveals an anti-adipogenic, anti-lipogenic, ß-oxidation effects of SPE in vivo and represents AMP-activated protein kinase signaling as targets for SPE.

Tetracera loureiri Extract Regulates Lipopolysaccharide-Induced Inflammatory Response Via Nuclear Factor-κB and Mitogen Activated Protein Kinase Signaling Pathways.

Tetracera loureiri (T. loureiri) is a woody climber inhabiting open deciduous or evergreen forests in Southeast Asia. A decoction comprising its stem and other herbs is a traditional Thai remedy for fatigue and jaundice, as well as to promote overall health. Anti-inflammatory effects induced by T. loureiri extract have not been reported. In this study, we investigated the anti-inflammatory effect of an ethanol extract of T. loureiri (ETL) on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophages. We found that ETL treatment inhibited the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells, without affecting cell viability. The effect of ETL on the expression of various pro-inflammatory mediators was analyzed using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). We observed that ETL inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels and decreased the production of prostaglandin E2 (PGE2) by COX-2 in RAW264.7 macrophages. ETL dose-dependently reduced the production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells, in a dose-dependent manner. Furthermore, ETL suppressed the LPS-induced nuclear translocation of the nuclear factor, NF-κB. Additionally, ETL was found to inhibit the activation of mitogen-activated protein kinases (MAPK), such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and p38 MAPK. In conclusion, our findings demonstrate that ETL inhibits the expression of pro-inflammatory mediators and cytokines, thereby downregulating NF-κB and MAPK signaling pathways in LPS-stimulated macrophages, Consequently, ETL is a potential therapeutic agent for the treatment of inflammatory diseases.

Improvement of Obesity and Dyslipidemic Activity of Amomum tsao-ko in C57BL/6 Mice Fed a High-Carbohydrate Diet.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

Monoterpenoids from the Fruits of Amomum tsao-ko Have Inhibitory Effects on Nitric Oxide Production.

In our search for novel plant-derived inhibitors of nitric oxide (NO) with potential for treating inflammatory diseases, the phytochemicals of Amomum tsao-ko fruits were investigated, leading to the isolation of one bicyclic nonane (1), three menthene skeleton monoterpenoids (2-4), and two acyclic monoterpenoids (5 and 6). Their structures were identified using one- and two-dimensional nuclear magnetic resonance spectroscopy, and mass spectrometry. To the best of our knowledge, compounds 2-5 were obtained from the genus Amomum for the first time. All isolates were tested for their ability to inhibit lipopolysaccharide-stimulated NO overproduction in RAW264.7 cells. Compound 4 was found to inhibit NO production. Western blotting analysis indicated that active compound 4 can regulate inducible NO synthase expression. In addition, lipopolysaccharide-induced interleukin 1 beta and interleukin-6 overproduction was reduced in a concentration-dependent manner.

Wheat Bran Extract Regulates Mast Cell-Mediated Allergic Responses In Vitro and In Vivo.

In the present study the effects and molecular mechanisms of wheat bran (WB), the hard outer layer of the wheat kernel used in food ingredients, on mast cell-mediated allergic responses in vitro and in vivo were investigated. The water extract of WB inhibited degranulation and expression of allergic and inflammatory mediators such as tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase in antigen-stimulated RBL-2H3 cells. These anti-allergic activities of WB were mediated by the inactivation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, which play important roles in degranulation and expression of various allergic and inflammatory molecules. In agreement with its in vitro effects, WB inhibited immunoglobulin E (IgE)/antigen-induced and compound 48/80-induced anaphylactic reactions in vivo. Taken together, these findings suggest the pharmacological potential of WB in the regulation of allergic diseases, including allergic rhinitis, atopic dermatitis, asthma and anaphylaxis.

Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Sustainable Low-Temperature Hydrogen Production from Lignocellulosic Biomass Passing through Formic Acid: Combination of Biomass Hydrolysis/Oxidation and Formic Acid Dehydrogenation.

Hydrogen production from renewable resources, such as lignocellulosic biomass, is highly desired, under the most sustainable and mildest reaction conditions. In this study, a new sustainable three-step process for the production of hydrogen has been proposed. In the first step, a crude formic acid (CF) solution, which included typical reaction byproducts, in particular, acetic acid, levulinic acid, saccharides, 5-hydroxymethylfurfural, furfural, and lignin, was obtained through the combined hydrolysis/oxidation of the biomass, in the presence of diluted sulfuric acid/hydrogen peroxide, as homogeneous catalysts. In the second one, the distilled formic acid (DF) solution was obtained by distillation of the CF solution, for example, by isolating liquid byproducts, or the lignin-free CF (LCF) solution was recovered by CF filtration for the elimination of only solid lignin particles. In the final step, hydrogen was produced from the DF or LCF solutions through formic acid dehydrogenation over Pd supported on amine-functionalized mesoporous silica catalysts, in the presence of sodium formate, as an additive. The clean hydrogen, which is produced from biomass passing through formic acid, could be applied as an energy source of fuel cells. This new hydrogen production process is smart, allowing the hydrogen production with mild reaction conditions, eventually starting from different lignocellulosic feedstocks, and it could be integrated within the existing hydrothermal technology for levulinic acid production, which has been already recognized as efficient and sustainable. In addition to the production of hydrogen as an energy source of fuel cells, formic acid derived from biomass could be utilized as a platform chemical for chemical, agricultural, textile, leather, pharmaceutical, and rubber industries.

Korean red ginseng water extract alleviates atopic dermatitis-like inflammatory responses by negative regulation of mitogen-activated protein kinase signaling pathway in vivo.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Korean red ginseng is a Korean traditional medicine. In this study, we estimated the effects of Korean red ginseng water extract (RGE) in the 1-chloro-2,4-dinitrobenzene (DNCB)-induced BALB/c mouse model which develops AD-like lesions. After RGE administration (100, 200, and 400 mg/kg) to DNCB-induced mice there were improvements in the dermatitis score and skin pH, a decrease in trans-epidermal water loss, and improved skin hydration. RGE also significantly inhibited eosinophil infiltration, increased filaggrin protein levels, and decreased serum IgE levels, epidermal thickness, mast cell infiltration, and ceramidase release. Compared with that in DNCB-induced mice, RGE effectively decreased the mRNA expression levels of interleukin-6 (IL-6), thymic stromal lymphopoietin (TSLP), and tumor necrosis factor-α (TNF-α), as well as the protein level of thymus and activation-regulated chemokine (TARC). These inhibitory RGE effects are mediated by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Furthermore, we confirmed that RGE suppresses interferon-γ (IFN-γ) and TNF-α-induced expression of macrophage-derived chemokine (MDC) and TARC genes in human keratinocyte (HaCaT) cells. Taken together, these results demonstrate that RGE may exert anti-atopic related to responses by suppression the expression of inflammatory mediators, cytokines, and chemokines via downregulation of MAPK signaling pathways, suggesting that RGE may be an effective therapeutic approach for prevention of AD-like disease.

Antihyperlipidemic Activity of Ligularia fischeri Extract in Mice Fed a High-Carbohydrate Diet.

Ligularia fischeri, indigenous to eastern Asia, has been used as a traditional herbal medicine. Ligularia fischeri reportedly possesses a number of biological activities such as antimutagenic, antioxidant, antigenotoxic, and anti-inflammation. This study demonstrated the effects of ethanol extracts of Ligularia fischeri (ELF) on a high-carbohydrate diet (HCD)-induced hyperlipidemia in C57BL/6 mice. The mice were divided into six groups (n = 7/group) as follows: normal diet, HCD, or HCD+ELF (100, 200, 400, and 800 mg/kg/day), which were orally administered daily for 12 weeks. Various lipid parameters and histological changes in liver and fat tissue were compared among the treatment and control groups. ELF remarkably reduced body weight gain and attenuated hyperlipidemia by improving the plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, atherogenic index, and cardiac risk factor. Moreover, ELF decreased the HCD-induced hepatic accumulation of lipid droplets and adipocyte hypertrophy. These regulatory effects of ELF appeared to be mediated through the phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, sterol regulatory element-binding protein-1c, and expression of fatty acid synthase. Taken together, these findings indicate a functional role for ELF in the regulation of HCD-induced obesity and hyperlipidemia.

Anti-melanogenic and anti-oxidant activities of ethanol extract of Kummerowia striata: Kummerowia striata regulate anti-melanogenic activity through down-regulation of TRP-1, TRP-2 and MITF expression.

Kummerowia striata (K. striata) is used as a traditional medicine for inflammation-related therapy. To determine whether it has beneficial anti-melanogenic and anti-oxidant activities, we investigated the biological activities of the ethanol extract of Kummerowia striata (EKS) using a variety of in vitro and cell culture model systems. The anti-melanogenic activity was assessed in B16F10 melanoma cells in terms of melanin synthesis and in vitro tyrosinase inhibitory activity. The anti-oxidant assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). EKS showed strong anti-oxidant activities in DPPH and ABTS assays. The mRNA transcription levels and protein expression levels of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor decreased in a dose-dependent manner with EKS treatment. Additionally, EKS did not affect cell viability at different concentrations used in this study, indicating that the mechanism of action of EKS-mediated inhibition of melanin synthesis does not involve cytotoxicity. Also, we confirmed that p-coumaric acid and quercetin are important compounds for anti-melanogenesis and antioxidant properties of EKS. Collectively, our findings demonstrate for the first time that EKS possesses anti-melanogenic and anti-oxidant activities. Further evaluation and development of EKS as a functional supplement or cosmetic may be useful for skin whitening and reducing wrinkles.

Kobophenol A Isolated from Roots of Caragana sinica (Buc'hoz) Rehder Exhibits Anti-inflammatory Activity by Regulating NF-κB Nuclear Translocation in J774A.1 Cells.

Kobophenol A (KPA) is a biologically active natural compound isolated from the roots of Caragana sinica (Buc'hoz) Rehder (C. sinica). However, the anti-inflammatory effects of KPA have not been reported. This study aims to find out whether KPA isolated from roots of C. sinica can act as a potential substance on inflammation and analyze the molecular mechanism using the lipopolysaccharide (LPS)-stimulated J774 A.1 macrophage cell line. We showed that KPA treatment significantly suppressed the production of nitric oxide (NO) by inhibiting inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner without cytotoxicity. In the KPA also inhibited pro-inflammatory cytokine gene expression and production, such as interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in LPS-stimulated J774 A.1 cells. As continuing study on the mechanisms involved, we confirmed that these effects of KPA were related to the inhibition of nuclear factor-κB (NF-κB) pathway including the suppression of IκB kinase α/ß (IKKα/ß) phosphorylation and translocation of NF-κB into the nucleus. Taken together, the present study is the first to demonstrate that KPA isolated from C. sinica suppresses the expression of inflammatory mediators and cytokines by inhibiting NF-κB nuclear translocation in LPS-stimulated J774 A.1 macrophages. KPA may be a potential candidate for the treatment of inflammatory diseases in the future.

Mesoporous Silica Supported Pd-MnOx Catalysts with Excellent Catalytic Activity in Room-Temperature Formic Acid Decomposition.

For the application of formic acid as a liquid organic hydrogen carrier, development of efficient catalysts for dehydrogenation of formic acid is a challenging topic, and most studies have so far focused on the composition of metals and supports, the size effect of metal nanoparticles, and surface chemistry of supports. Another influential factor is highly desired to overcome the current limitation of heterogeneous catalysis for formic acid decomposition. Here, we first investigated the effect of support pore structure on formic acid decomposition performance at room temperature by using mesoporous silica materials with different pore structures such as KIE-6, MCM-41, and SBA-15, and achieved the excellent catalytic activity (TOF: 593 h-1) by only controlling the pore structure of mesoporous silica supports. In addition, we demonstrated that 3D interconnected pore structure of mesoporous silica supports is more favorable to the mass transfer than 2D cylindrical mesopore structure, and the better mass transfer provides higher catalytic activity in formic acid decomposition. If the pore morphology of catalytic supports such as 3D wormhole or 2D cylinder is identical, large pore size combined with high pore volume is a crucial factor to achieve high catalytic performance.

Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation.

The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

Decrease in the urine cotinine concentrations of Korean non-smokers between 2009 and 2011 following implementation of stricter smoking regulations.

This study aimed to determine if there was an association between the implementation of smoking regulation policies and the urine cotinine concentrations of Korean non-smokers. The subjects of this study were 4612 non-smoking Korean citizens (aged 19 or older) selected from the first stage of the Korean National Environmental Health Survey conducted by the National Institute of Environmental Research from 2009 to 2011. Cotinine concentrations in urine were measured by GC-MS (limit of detection: 0.05 ng/mL). Changes in the urine cotinine concentration were analyzed using a weighted general linear model and linear regression and values were shown as geometric mean (GM). The GM urine cotinine concentration decreased over time (2.92 ng/mL in 2009, 1.93 ng/mL in 2010, and 1.25 ng/mL in 2011). The total decrease in the subjects' urine cotinine concentration between 2009 and 2011 was 2.79 ng/mL, representing a relative decrease of 54.7%. The decrease in GM urine cotinine concentration in each subgroup ranged from 2.17 ng/mL to 3.29 ng/mL (relative decreases of 46.4% and 62.8%, respectively), with the largest absolute reductions in subjects in the following groups: females, aged 40-49 years, detached residence type, no alcohol consumption, employed, secondhand smoke exposure. All groups had negative regression coefficients, all of which were significant (p < 0.001). Our results provide indirect indicators of the effectiveness of smoking regulation policies including the revision of the National Health Promotion Act in Korea.

Decline in non-smoking workers' urine cotinine levels after increased smoking regulation in Korea.

OBJECTIVES: To identify any association between implementing smoking regulation policies and workers' urine cotinine concentration levels in Korea. METHODS: From the first stage of the Korean National Environmental Health Survey conducted by the National Institute of Environmental Research from 2009 to 2011, 2,475 non-smoking workers selected. We analyzed the trend in the changes of cotinine concentration in urine using the general linear model and linear regression, in various jobs as categorized by the National Center for Health Statistics (NCHS) and Korea Standard Classification of Occupations (KSCO). RESULTS: The urine cotinine concentration tended to decrease every year (2.91 ng/ml in 2009, 2.12 ng/ml in 2010, and 1.31 ng/ml in 2011), showing a decreasing trend (P < 0.001). The total subjects' decreased cotinine concentration in urine between 2009 and 2011 was 2.72 ng/ml (54.1 % relative decrease). The changes in each subgroup's urine cotinine concentration ranged from 1.59 to 6.03 ng/ml (33.2 to 77.5 %). All groups except for the managerial group (n = 49), which had a small sample size, had statistically significant negative regression coefficients (p < 0.05). The ranges of the decrease in urine cotinine were 2.75 ng/ml (53.6 %) for males and 2.72 ng/ml (54.9 %) for females. The negative slope in urine cotinine level was statistically significantly greater in men than women. The changes in urine cotinine by occupation as classified by the NCHS occupational categories ranged from 2.43 to 3.36 ng/ml (46.6 to 61.5 % relative decrease). The negative slopes in urine cotinine levels of the white-collar and farm workers were statistically significantly greater than those of the service workers and blue-collar workers. The change by occupation as classified by the KSCO ranged from 1.59 to 6.03 ng/ml (a 33.2 to 77.5 % relative decrease). The negative slopes in urine cotinine levels of the professionals and related workers and clerks were statistically significantly greater than those of the service workers and plant and machine operators and assemblers. CONCLUSIONS: The cotinine concentration in urine among non-smoking worker groups tended to decline from 2009 to 2011. Such a result may be an indirect indicator of the effectiveness of smoking regulation policies including the revision of the National Health Promotion Act.