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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.

Periodontitis, a disease caused by inflammation of oral bacteria, contributes to the loss of alveolar bone and destruction of connective tissues. Porphyromonas gingivalis, a Gram-negative bacterium, is known to possess important pathogenic factors for periodontal disease. In this study, we investigated the anti-periodontitis effects of Magnolia kobus extract (MKE) and magnolin as a component of Magnolia kobus (MK) in murine macrophage RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Effects of MKE and magnolin on the mechanism of RAW 264.7 cellular inflammation were determined by analyzing nitric oxide (NO) production and Western blot protein expression (n = 3). MKE/magnolin inhibited NO production without affecting cell survival. MKE/magnolin treatment inhibited LPS-induced pro-inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs such as MMP-1, 3, 8, 9, and 13), and protein levels of inflammatory mediators (such as TNF-α, IL-1β, and mPGES-1). MKE/magnolin also suppressed NF-κB activation by inhibiting the TLR4 signaling pathway. These findings suggest that MKE has a therapeutic effect on inflammatory periodontal disease caused by oral bacterium P. gingivalis and that magnolin is a major functional component in the anti-inflammatory effect of MKE.

Dyglomera® is an aqueous ethanol extract of the fruit pods of Dichrostachys glomerata, a Cameroonian spice. Several studies have shown its anti-diabetic and anti-obesity effects. However, the underlying mechanisms for such effects remain unclear. Thus, the objective of this study was to investigate the anti-obesity effect of Dyglomera® and its underlying mechanisms in mice with high-fat diet-induced obesity and 3T3-L1 adipocytes. Our results revealed that Dyglomera® inhibited adipogenesis and lipogenesis by regulating AMPK phosphorylation in white adipose tissues (WATs) and 3T3-L1 adipocytes and promoted lipolysis by increasing the expression of lipolysis-related proteins. These results suggest that Dyglomera® can be used as an effective dietary supplement for treating obesity due to its modulating effect on adipogenesis/lipogenesis and lipolysis.

Dyglomera

This paper reports the newly measured experimental data for CO2 solubility in a blended aqueous solution of monoethanolamine (MEA) and 2-amino-2-methyl-propanol (AMP) at different amine mixing ratios (MEA/AMP/H2O = 9:21:70, 15:15:70, and 21:9:70 wt %) and working temperatures (323.15, 373.15, and 383.15 K). The successive substitution method was used for calculating the mole fractions of all molecules (four molecules) and electrolytes (three cations and four anions) from the equilibrium along with the material and charge balance equations (11 equations). The electrolyte nonrandom two-liquid (e-NRTL) model was used to investigate nonideality in the liquid phase. Using the abovementioned thermodynamic models, the partial pressures of CO2 in the gas phase, mole fractions of all components in the liquid phase, pH variations, heats of absorption, and cyclic capacities of CO2 according to the absorption/desorption temperature and the blending ratio of MEA/AMP were estimated.

Since the potential of (3:1) mixtures of Atractylodes macrocephala and Amomum villosum extracts has been proposed in the management of obesity, the purpose of present study was to investigate the effects of AME:AVE (3:1) mixture on weight loss, obesity-related biochemical parameters, adipogenesis and lipogenesis related proteins in 3T3-L1 cells and HFD-induced obesity in a mouse model. Treatment with AME:AVE (3:1) mixture inhibited lipid accumulation. Furthermore, the treatment with 75 and 150 mg/kg of AME:AVE (3:1) significantly decreased the body weight gain, white adipose tissue (WAT) weight, and plasma glucose level in HFD-induced obese mice. Moreover, treatment with 75 and 150 mg/kg AME:AVE (3:1) also significantly lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. AME:AVE (3:1) treatment significantly decreased the expression of proteins related to adipogenesis and lipogenesis in 3T3-L1 adipocytes and WAT of HFD-induced obese mice. These results suggest that the AME:AVE herbal mixture (3:1) has anti-obesity effects, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related proteins in adipocytes and WAT in HFD-induced obesity in mice.

Since the potential of (3:1) mixtures of

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation, which is the most common form of chronic liver disease. Multiple clinical studies using natural compounds such as flavonoids have been conducted to treat NAFLD. In the present study, the pharmacological effect of Citrus aurantium L. (Rutaceae) peel extract (CAE), which contains over 27% of polymethoxyflavone nobiletin, on NAFLD was evaluated using a high-fat diet (HFD) animal model susceptible to developing NAFLD. C57BL/6 mice were fed an HFD (60% kcal of energy derived from fat) for 8 weeks to induce obesity. Obese mice were randomly allocated to four groups of eight mice each (HFD alone, HFD with silymarin, HFD with 50 mg/kg CAE, and HFD with 100 mg/kg CAE). After 8 weeks of treatment, all mice were euthanized, and plasma and liver tissues were analyzed biochemically and histopathologically. The results indicate that CAE treatment significantly reduced HFD-induced NAFLD, as shown by decreased serum lipid index and prevented liver histopathology. The expression of genes involved in lipid synthesis including free fatty acid (FFA), peroxisome-proliferator-activated receptor γ (PPAR-γ), sterol receptor element binding protein 1c (SREBP-1c), and fatty acid synthesis enzyme was suppressed by CAE treatment. Moreover, compared to untreated mice, CAE-treated HFD mice showed decreased pro-inflammatory cytokine expression. These results demonstrated that CAE prevented HFD-induced NAFLD by reducing plasma levels of triglyceride and cholesterol and de novo lipid synthesis.

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 β-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 β-oxidation. The present study reveals an anti-adipogenic, anti-lipogenic, β-oxidation effects of SPE in vivo and represents AMP-activated protein kinase signaling as targets for SPE.

Osteoarthritis (OA) is a general joint illness caused by the destruction of joint cartilage, and is common in the population of old people. Its occurrence is related to inflammatory reactions and cartilage degradation. AyuFlex&reg, is an aqueous extract of Terminalia chebula fruit, and T. chebula has been utilized extensively in several traditional oriental medications for the management of diverse diseases. Pre-clinical and clinical research has shown its antioxidant and anti-inflammatory effectiveness. Nevertheless, the mechanism underlying the anti-arthritic effects of AyuFlex&reg, remains unclear. In the current research, we proposed the ameliorating effects of AyuFlex&reg, with respect to the incidence of OA and described the latent signalization in interleukin (IL)-1&beta, treated chondrocytes and MIA-incurred OA in a rat model. In vitro, AyuFlex&reg, decreased oxidative stress and induction of pro-inflammatory cytokines and mediators as well as matrix metalloproteinases (MMPs), while also increasing the levels of collagen synthesis-related proteins. Mechanistically, we identified that AyuFlex&reg, disrupted nuclear factor kappa B (NF-&kappa, B) and mitogen-activated protein kinase (MAPK) activation via the inhibition of NF-&kappa, B p65 and extracellular regulated protein kinase (ERK) phosphorylation. The ameliorating effects of AyuFlex&reg, were also observed in vivo. AyuFlex&reg, significantly inhibited the MIA-incurred increase in OA symptoms such as oxidative stress, cartilage damage, and changes in cytokines and MMPs revelation in arthrodial cartilage. Therefore, our results suggest that AyuFlex&reg, attenuates OA progression in vivo, indicating that AyuFlex&reg, can be suggested as an excellent therapeutic remedy for the care of OA.

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally administered once per day for three weeks. Weight-bearing distribution and arthritis index (AI) were measured once per week to confirm the OA symptoms. Synovial membrane, proteoglycan layer, and cartilage damage were investigated by histological examination, while synovial fluid interleukin-1&beta, level was analyzed using a commercial kit. Levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the cartilage tissues were investigated to confirm the anti-osteoarthritic effects of LI73014F2. LI73014F2 significantly inhibited the MIA-induced increase in OA symptoms, synovial fluid cytokine, cartilage damage, and expression levels of pro-inflammatory mediators/cytokines and MMPs in the articular cartilage. These results suggest that LI73014F2 exerts anti-osteoarthritic effects by regulating inflammatory cytokines and MMPs in MIA-induced OA rats.

Osteoarthritis (OA) is one of the most well-characterized joint diseases and is associated with chondrocyte inflammation, metalloproteinase upregulation and apoptosis. LI73014F2 is a novel composition prepared from aqueous extract of Terminalia chebula fruit, alcohol extract of Curcuma longa rhizome, and Boswellia serrata extract at 2:1:2 ratio. Earlier studies have shown that LI73014F2 inhibits cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) activities, and attenuates clinical symptoms in OA subjects. In the present study, we evaluated the protective anti-inflammatory and anti-apoptotic effects, as well as the underlying mechanisms, of LI73014F2 in interleukin (IL)-1&beta, induced inflammation in human primary chondrocytes. Human chondrocytes were treated with LI73014F2 (0, 12.5, 25 and 50 &mu, g/mL) in IL-1&beta, (10 ng/mL)-containing chondrocyte growth medium for 24 h. Cell viability was assessed using an MTT assay. The pro-inflammatory mediator, inflammatory cytokines, MMPs, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) and nuclear factor-&kappa, B (NF-&kappa, B) signaling pathways protein expression levels were detected by western blot analysis. The results demonstrated that LI73014F2 normalized the expressions of COX-2, mPGES-1, PGE2, 5-LOX, LTB4, IL-1&beta, TNF&alpha, IL-6, MMP-2, MMP-3, MMP-9, MMP-13, Bax/Bcl-2, cleaved caspase-9 and -3, cleaved PARP, phospho-NF-&kappa, B p65 and phospho-p38 MAPK proteins in IL-1&beta, induced primary human chondrocytes. Moreover, the data suggested that LI73014F2 reduced IL-1&beta, induced inflammation and apoptosis, at least partially via the inhibition of the NF-&kappa, B/MAPK signaling pathway. In conclusion, the present findings provide the molecular basis of the anti-OA efficacy of LI73014F2.

The absorption mechanism of CO2 in an aqueous solution containing three alkanolamines was analyzed experimentally and theoretically. The vapor–liquid equilibrium of a CO2–monoethanolamine (MEA)–diisopropanolamine (DIPA)–2-amino-2-methyl-propanol (AMP)–H2O system was evaluated experimentally over a wide temperature range (323.15–393.15 K) at several MEA:DIPA:AMP:H2O blending ratios (15:10:5:70, 10:10:10:70, 7.5:7.5:15:70, and 5:15:10:70 wt%). The successive substitution method was used to calculate the concentrations of five molecules (CO2, MEA, DIPA, AMP, and H2O) and nine electrolytes (four cations and five anions) in the liquid phase by solving eight equilibrium equations, four mass balance equations, and one charge balance equation. The Deshmukh–Mather model, which is based on an activity coefficient approach, and the fugacity coefficient model were used to evaluate the nonideality of the liquid and vapor phases, respectively. Thereafter, the effect of the MEA:DIPA:AMP blending ratio was evaluated using the triangular diagrams of the carbamate, bicarbonate and carbonate molar fractions in liquid phase, CO2 loading ratio, CO2 cyclic capacity, and heat of CO2 absorption.

Highlights • CQR-300 inhibited lipid accumulation in 3T3-L1 adipocytes. • CQR-300 inhibited the differentiation of adipocytes by regulating adipogenesis. • CQR-300 reduced fatty acids and triglyceride accumulation via downregulating lipogenesis., The objective of this study was to evaluate the anti-obesity activity and the action mechanism of Cissus quadrangularis extracts (CQR-300) in 3T3-L1 adipocytes. Cissus quadrangularis was extracted with hot water, resulting in CQR-300. The anti-obesity activity of CQR-300 in 3T3-L1 adipocytes was examined by Oil-red O staining. Possible mechanisms of CQR-300 in 3T3-L1 adipocytes were determined by real-time PCR and western blot. Treatment with CQR-300 inhibited lipid accumulation without showing cytotoxicity to 3T3-L1 adipocytes. Furthermore, CQR-300 decreased adipogenesis/lipogenesis-related mRNA expression levels of fatty acid binding protein (aP2), fatty acid synthase (FAS), lipoprotein lipase (LPL), stearoyl-CoA desaturase-1 (SCD-1), and acetyl-CoA carboxylase (ACC). CQR-300 also down-regulated expression levels of adipogenesis/lipogenesis-associated proteins, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element binding protein-1c (SREBP-1c), and FAS. It’s also up-regulated the expression level of phosphorylated-AMPK (p-AMPK). Collectively, these results suggested that CQR-300 might have an anti-obesity effect by its ability to decrease expression levels of adipogenesis/lipogenesis-related genes and proteins.

Echinacea purpurea (EP) has been widely used to treat upper respiratory infections, influenza, and the common cold. It can also exert various pharmacological activities, such as anti-inflammatory and anti-allergic effects. However, the potential of EP to modulate immune reactions remains unclear. Therefore, we evaluated the immunostimulatory effects of EP in cyclophosphamide (CP)-induced immunosuppressed mice. In this study, EP extract (12.5, 25, or 50 mg/kg) was orally administered to cyclophosphamide-induced immunosuppressed BALB/c mice. Then, indexes of immune organs, including the spleen and thymus, were recorded. Splenocyte proliferation and natural killer (NK) cell activities were measured by lactate dehydrogenase assay. Subsets of T cells, such as CD4+ and CD8+, were measured by flow cytometry, and immuno-cytokines, such as interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, were measured by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. The immunosuppressed mice showed decreased thymus and spleen indexes and immune cell activities. Treatment of EP elevated the indexes of immune organs, splenocyte proliferation, and NK cell activities in CP-induced immunosuppressed mice. Simultaneously, administration of EP reversed the CP-induced decrease in T-lymphocyte subsets (CD4+ and CD8+) and immunocytokines (IL-2, TNF-α, and IFN-γ). Taken together, these findings suggest that EP could be used to enhance health and immunity in immunosuppressed conditions.

Experimental data on CO2 solubility in diisopropanolamine (DIPA) and methyldiethanolamine (MDEA) blended aqueous solutions were measured at different amine blending ratios and working temperatures. The successive (iterative) substitution method was implemented to calculate the molar fractions of all chemical species, including molecules and electrolytes, from equilibrium along with four material balances and one electroneutrality equation. The electrolyte universal quasi-chemical (electrolyte UNIQUAC) model was used to consider the nonideality in the liquid phase. The partial pressures of CO2 in the gas phase and molar fractions of all components in the liquid phase were recalculated using thermodynamic models. In addition, the effect of the blending ratio of DIPA, MDEA, and H2O was investigated and expressed using the newly applied triangular diagrams of pH, heat of absorption, and cyclic capacity of CO2 according to the absorption and stripping conditions.

Over the past decades, periodontitis has become a rising health problem and caused various diseases. In the many studies shows that some extracts and compound to the prevention and treatment of periodontitis. This study focuses on the effects of inhibition of gingival damage and alveolar bone loss. The aim of this study was to evaluate the protective effects of Magnolia biondii extract (MBE) against ligature-induced periodontitis in rats. A ligature was placed around the molar teeth for 8 weeks, and MBE was administered for 8 weeks. Gingival tissue damage and alveolar bone loss were measured by microcomputed tomography (CT) analysis and histopathological examination. Serum Interluekin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), cyclooxygenases-2 (COX-2), and receptor activator of nuclear factor–κB ligand (RANKL) levels were investigated using commercial kits to confirm the antiperiodontitis effects of MBE. We confirmed that ligature-induced periodontitis resulted in gingival tissue damage and alveolar bone loss. However, treatment for 8 weeks with MBE protected from periodontal tissue damage and downregulated serum inflammatory cytokine factors and RANKL levels. These results suggest that MBE exerts antiperiodontitis effects by inhibiting gingival tissue destruction and alveolar bone loss through regulation of anti-inflammatory cytokines in periodontitis-induced rats.

The aim of the present study was to evaluate the neuroprotective effect of Citrus aurantium extract (CAE) and nobiletin against amyloid β 1‑42 (Aβ 1‑42)‑induced spatial learning and memory impairment in mice. After injecting Aβ 1‑42 (5 µl/2.5 min, intracerebroventricular injection), amnesic mice were orally administered CAE and nobiletin for 28 days. Memory, spatial and cognitive ability were measured using passive avoidance and a Morris water maze task. Acetylcholinesterase (AchE) activity was investigated in the hippocampus and cortex using commercial kits and the analysis of Bax, Bcl‑2, and cleaved caspase‑3 protein expression by western blot assays was used to confirm the anti‑apoptotic mechanism of CAE and nobiletin. The present study confirmed impairments in learning and memory in the Aβ‑induced neurodegenerative mice with increased AchE activity in the brain. However, the daily administration of CAE and nobiletin reduced the spatial learning deficits and increased the AchE activity in the cortex and hippocampus. Furthermore, CAE and nobiletin significantly downregulated the Bax and cleaved caspase‑3 protein expression and upregulated the Bcl‑2 and Bcl‑2/Bax expression in the cortex and hippocampus of Aβ‑treated mice. These results suggest that CAE and nobiletin exert a neuroprotective effect by regulating anti‑apoptotic mechanisms, including reduced AchE activity in the cortex and hippocampus of the cognitive deficit mouse model.

In the present study, we explore the protective effects of Citrus aurantium L. extract (CAE) against acute and chronic CCl4-induced hepatotoxicity. The quantitative analysis of CAE was performed using HPLC-UV to determine the nobiletin content was approximately 27%. For the acute model, the male ICR mice were orally treated with water, silymarin (positive control, 200 mg/kg) and CAE (50 and 200 mg/kg) for 3 days prior to CCl4 (1 mL/kg, 50% v/v in olive oil) IP injection. For the chronic model (n = 6/group), the mice were treated with each treatment for 28 consecutive days and CCl4 (1 mL/kg, 20%) was injected twice a week. In both the acute and chronic models, the CCl4 alone treated group showed histopathologic alterations with a significantly increase in serum hepatic enzyme levels together with a disrupted anti-oxidative status. In contrast, the CAE treatments restored pathologic alterations and recovered the oxidative status by enhancing antioxidant enzymes and reducing lipid peroxidation levels. Furthermore, CAE enhanced nuclear factor E2-related factor 2 (Nrf2) and its related cytoprotective signals, including NAD(P)H quinone oxidoreductase 1, UDP-glucuronosyltransferase, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrates that CAE exerts a protective effect against CCl4-induced hepatotoxicity with its anti-oxidant, anti-inflammatory, and anti-apoptotic activity.

The current study investigated the anti-obesity effect of Cissus quadrangularsis extracts (CQR-300) and its molecular action mechanism on obese mice induced high-fat diet (HFD). To induce the obesity, mice were fed a HFD for 6 weeks and then fed HFD only or HFD with CQR-300 at 50 and 200 mg/kg. Then, body weight gain and white adipose tissue weights were measured. We investigated the reduction in body fat and the regulation of fatty acid synthesis was measured by dual energy X-ray absorptiometry and real-time PCR with Western blot, respectively. In vitro study, CQR-300 inhibited pancreatic lipase activity. The CQR-300 treatment was significantly decreased the body weight gain and adipocytes size as well as white adipose tissues weights in HFD-induced obese mice. Furthermore, CQR-300 reduced the body fat and fat mass with regulating of adipose tissue hormones as leptin. Treatment with 50 mg/kg CQR-300 showed effectively lower expression levels of adipogenesis/lipogenesis related genes and proteins such as CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), Sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) in white adipose tissue (WAT) as compared with the HFD fed only mice. These results suggest that the CQR-300 has an anti-obesity effect via inhibition of lipase activity, decrease the body fat mass by regulating the adipogenesis and lipogenesis related genes and proteins in epididymal adipose tissue with evaluate body fat reduce in the HFD-induced obese mice.

In this study, we optimized fermentation conditions for the solid state fermentation of rice bran with Monascus pilosus KCCM60084, and the antioxidant activities were investigated. Optimal fermentation conditions were determined by the production of Monacolin K, a functional secondary metabolites with cholesterol lowering activity. The highest Monacolin K production were 2.88 mg/g observed on day 10 with 45% moisture content in the substrate when inoculated with 5% inoculum (w/w). Reducing power, iron chelating activity and ABTS + radical scavenging activity were significantly enhanced after fermentation by 60, 80, and 38% respectively. Furthermore, the content of total flavonoid were found to be increased by 4.58 fold. Based on these results, Monascus-fermented rice bran showed strong possibility to be used as a natural antioxidant agent due to its enhanced antioxidant activity.

Objective To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in high-fat diet (HFD)–induced obese mice and 3T3-L1 adipocytes. Methods The roots of Adenophora triphylla were extracted with 70% ethanol. To demonstrate the compounds, linoleic acid was analyzed by using gas chromatography; and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese mice. Results Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 adipocytes. Furthermore, 200 and 400 mg/kg ATE treatment significantly decreased the body weight gain, white adipose tissues (WATs) weight and plasma triglyceride level, while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice, as compared with the HFD group. Treatment with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. ATE treatment showed significantly lower expression level of adipogenesis-related proteins, such as peroxisome proliferator-activated receptor γ, fatty acid binding protein (aP2), fatty acid synthase in 3T3-L1 adipocytes; and furthermore, decreased peroxisome proliferator-activated receptor γ, aP2, fatty acid synthase, sterol regulatory element binding protein-1c, and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese mice. Conclusions These results suggested that the ATE has an anti-obesity effect, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor-α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor E2-related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti-inflammatory, and antiapoptotic activity against ethanol-induced liver injury.

Four maleic anhydride derivatives, tricladolides A-D (1-4), and three alkylidene succinic acid derivatives, tricladic acids A-C (5-7), were isolated from the aquatic hyphomycete Tricladium castaneicola. The structures of these compounds were determined by spectroscopic analysis, and all were found to be novel. The compounds exhibited inhibitory activity against fungi, particularly Phytophthora sp., a plant pathogen of oomycetes. The inhibitory activity of these metabolites revealed the importance of the cyclic anhydride structure and the lipophilicity of the alkyl side chain. On the other hand, the cytotoxicity of the compounds against B16 melanoma cells indicated that the cyclic anhydride structure was not essential.

Over the past decades, periodontitis has become a rising health problem and caused various diseases. In the many studies shows that some extracts and compound to the prevention and treatment of periodontitis. This study focuses on the effects of inhibition of gingival damage and alveolar bone loss. The aim of this study was to evaluate the protective effects of Magnolia biondii extract (MBE) against ligature-induced periodontitis in rats. A ligature was placed around the molar teeth for 8 weeks, and MBE was administered for 8 weeks. Gingival tissue damage and alveolar bone loss were measured by microcomputed tomography (CT) analysis and histopathological examination. Serum Interluekin-1 &beta, (IL-1&beta, ), tumor necrosis factor-&alpha, (TNF-&alpha, ), cyclooxygenases-2 (COX-2), and receptor activator of nuclear factor&ndash, &kappa, B ligand (RANKL) levels were investigated using commercial kits to confirm the antiperiodontitis effects of MBE. We confirmed that ligature-induced periodontitis resulted in gingival tissue damage and alveolar bone loss. However, treatment for 8 weeks with MBE protected from periodontal tissue damage and downregulated serum inflammatory cytokine factors and RANKL levels. These results suggest that MBE exerts antiperiodontitis effects by inhibiting gingival tissue destruction and alveolar bone loss through regulation of anti-inflammatory cytokines in periodontitis-induced rats.

A library of extracts established from hundreds of marine organisms was screened by a cytotoxicity test. The active organic extract of an Okinawan marine sponge of the genus Dysidea was subjected to bioassay-guided fractionation to give three new polyoxygenated steroids dysideasterols F-H (1-3), together with two known related compounds (4 and 5). Their structures were confirmed by NMR and mass spectroscopic analyses. A characteristic structural feature of 2, 4 and 5 is an allylic epoxide, whereas this epoxide undergoes ring-opening by a neighbouring hydroxyl group to give a tetrahydrofuran ring in 1 and 3. All compounds 1-5 exhibited a similar cytotoxic effect with IC50 values of 0.15-0.3 µM against human epidermoid carcinoma A431 cells, demonstrating that the allylic epoxide moiety was not responsible for this cytotoxic effect.

The dried flower buds of Magnolia sp. are widely used as herbal medicines because of their anti-inflammatory, anti-malarial and anti-platelet activities. Here, we found that veraguensin and galgravin, lignan compounds derived from Magnolia sp., dose-dependently inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblastic cells. These compounds also inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells and bone marrow macrophages. In the RANKL-induced signaling pathway, veraguensin and galgravin reduced p38 phosphorylation and suppressed the expression of c-Fos, a key transcription factor for osteoclastogenesis. Veraguensin and galgravin also inhibited osteoclastic pit formation, which was accompanied by decreased mature osteoclast viability. In conclusion, these results indicate that veraguensin and galgravin can inhibit bone resorption and may offer novel compounds for the development of drugs to treat bone-destructive diseases such as osteoporosis.

Citrus depressa Hayata (commonly known as shiikuwasa) is cultivated in the northern areas of Okinawa, Japan, and used as a juice. In this study, we examined the anti-obesity effects and mechanism of action of shiikuwasa peel extract (SE) using high-fat diet (HFD)-induced obese mice. Mice were fed a low-fat diet (LFD), HFD or HFD containing 1% or 1.5% (w/w) SE (HFD+1 SE and HFD+1.5 SE, respectively) for 5 weeks. The body weight gain and white adipose tissue weight were significantly decreased in the HFD+1.5 SE group compared with the HFD group. The plasma triglyceride and leptin levels were also significantly reduced in the HFD+1.5 SE group compared with the HFD group. Histological examinations showed that the sizes of the adipocytes were significantly smaller in the HFD+1.5 SE group than in the HFD group. The HFD+1.5 SE group also showed significantly lower mRNA levels of lipogenesis-related genes, such as activating protein 2, stearoyl-CoA desaturase 1, acetyl-CoA-carboxylase 1, fatty acid transport protein and diacylglycerol acyltransferase 1, than the HFD group. These results suggest that the anti-obesity effects of SE may be elicited by regulating the expressions of lipogenesis-related genes in white adipose tissue.

Objective To explore the anti-obesity effects and the mechanism of action of Monascus pilosus ( M. pilosus )-fermented black soybean (MFBS) extracts (MFBSE) and MFBS powders (MFBSP) in adipocytes and high-fat diet (HFD)-induced obese mice, respectively. Methods Black soybean was fermented with M. pilosus , and the main constituents in MFBS were analyzed by HPLC analysis. In vitro , MFBSE were examined for anti-adipogenic effects using Oil-Red O staining. In vivo , mice were fed a normal-fat diet (NFD) control, HFD control or HFD containing 1 g/kg MFBSP for 12 weeks, and then body weight gain and tissues weight measured. Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects. Results MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity. MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice. MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes, such as peroxisome proliferator-activated receptor γ( PPAR γ), fatty acid-binding protein 4 ( FABP4 ), and fatty acid synthase ( FAS ), in adipocytes and in white adipose tissue (WAT) of HFD-induced obese mice. Conclusions These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFD-induced obese mice.

Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor-α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor E2-related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti-inflammatory, and antiapoptotic activity against ethanol-induced liver injury.

Very recently the unforeseen role of syndecan 3 (SDC3), a family of membrane-bound heparin sulfate proteoglycans, in the regulation of energy balance has been discovered in the Sdc3 null female mice.The objective of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) in SDC3 are associated with obesity in the Korean population.We conducted a population-based cohort study consisting of 229 control and 245 study subjects and a second independent study consisting of 192 control and 115 study subjects.Body mass index (BMI) was measured.First, Sdc3 mRNA expression in the brain of ob/ob mice was profoundly increased, compared with control mice. Next, all three nonsynonymous SNPs [T271I (rs2282440, CT), D245N (rs4949184, CT), and V150I (rs2491132, CT)] in the SDC3 gene in control female subjects (BMI23, n = 229) and obese female subjects (BMI30, n = 245) were genotyped. We demonstrated the presence of clear ethnic differences in three nonsynonymous SDC3 SNPs among African-Americans, Chinese, Europeans, and Koreans. Of three SNPs in SDC3, rs4949184 was not associated with obesity and the other two SNPs (rs2282440 and rs2491132) were strongly associated with obesity (P0.0001), and the results were confirmed in the second independent study group. Haplotype analysis also revealed strong association with obesity (chi2 = 76.92, P0.000001).There are ethnic differences in the SDC3 polymorphisms, and the polymorphisms are strongly associated with obesity.

In this study, tomentosin, a sesquiterpene lactone was isolated from Inulae flos and its biological activities were investigated. The effects of tomentosin on the production of inflammatory mediators as well as on nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW264.7 cells. Tomentosin decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally, tomentosin reduced the release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Tomentosin not only attenuated lipopolysaccharide (LPS)-induced NF-κB activation via the abrogation of inhibitory (I)κBα degradation and caused a subsequent decrease in nuclear p65 level, but it also suppressed the phosphorylation of MAP kinases (p38 and c-Jun N terminal kinase (JNK)). These results indicate that tomentosin exerts anti-inflammatory activities through the inhibition of inflammatory mediators (NO, iNOS, PGE2, COX-2, TNF-α, and IL-6) by regulating NF-κB activation and phosphorylation of p38/JNK kinases in macrophages, thus suggesting that tomentosin could be a potential agent for the treatment of inflammatory diseases.

The purpose of this study was to determine the usefulness of magnetic resonance imaging (MRI) for distinguishing spinal involvement of hematopoietic malignancies (lymphoma, leukemia, and multiple myeloma) from metastasis. 62 spinal MRIs were obtained in 60 patients with hematopoietic malignancies (n = 24) and metastasis (n = 36) in clinically and pathologically proven cases. MRI findings were evaluated in each group of patients for the pattern of involvement, signal change of vertebral body, location of paraspinal mass formation, location of epidural mass formation, cortical destruction, contour change, and compression fracture. Diffuse involvements were more commonly seen in hematopoietic malignancies than in metastasis (p < 0.05). Signal change confined to anterior element was seen in 9 metastasis but was not seen in hematopoietic malignancies. Cortical destructions were more commonly seen in metastasis than in hematopoietic malignancies (p < 0.05). Other findings did not show any statistical significance in both groups. MRI findings such as diffuse involvement, posterior epidural mass formation, and cortical destruction were useful to distinguish spinal involvement of hematopoietic malignancies and metastasis.

Using B16 melanoma cells for screening, we found that a marine sponge extract has a potent anti-pigmenting effect and identified arenarol as its major active compound. In normal human melanocytes (NHMs), arenarol significantly abrogated the endothelin 1 (EDN1) stimulated expression of tyrosinase, tyrosinase-related protein 1 and dopachrome tautomerase at the transcriptional, translational and enzymatic activity (only for tyrosinase) levels. That effect was accompanied by the attenuation of the increased expression level of microphthalmia-associated transcription factor (MITF) protein at the transcriptional and translational levels. Analysis of EDN1 signaling demonstrated that arenarol significantly suppressed the EDN1-induced phosphorylation of MEK, ERK, MITF and CREB but not of Raf-1s. In contrast, the forskolin-induced phosphorylation of CREB was not down-regulated by arenarol. As for the mode of action of the suppressed phosphorylation of MEK, Raf-1 activity was not directly inhibited by arenarol in vitro and pretreatment with the protein phosphatase inhibitor okadaic acid did not affect the down-regulated phosphorylation of MEK that was induced by arenarol in NHMs. The sum of these findings suggests that arenarol abrogates the EDN1-stimulated expression of melanocyte-specific proteins by interrupting MEK phosphorylation in an as yet unknown Raf-1 inactivation mechanism.

Platelet-derived growth factor (PDGF) induces the proliferation and migration of vascular smooth muscle cells (VSMCs), leading to the development of various vascular disorders such as restenosis and atherosclerosis. Therefore, inhibitors of PDGF-induced cellular events would be candidate agents for treating these diseases. During the search for such inhibitors from marine sources, we isolated petrosiols A–D ( 1 – 4 ) and related compounds from the marine sponge Petrosia strongylata. These metabolites, which we previously reported as neurotrophic substances, showed an inhibitory effect on PDGF-induced DNA synthesis at IC 50 values of 0.69–2.2 μM. Petrosiol A ( 1 ) inhibited PDGF-induced cell proliferation without remarkable cytotoxicity and arrested cell cycle progression from the G0/G1 to S phase by inducing the downregulation of the expression of G1 checkpoint proteins cyclin D1, cyclin E, cyclin-dependent kinases (CDK)2, and CDK4 and the upregulation of the expression of p21 and p27. In addition, petrosiol A ( 1 ) inhibited the phosphorylation of PDGF receptor-β and its downstream proteins such as phospholipase C (PLC)-γ1, Akt, and extracellular signal-regulated kinase (ERK)1/2. These results suggest that 1 inhibited PDGF-induced VSMC proliferation by interrupting the phosphorylation of PDGF receptor-β followed by downstream signal transduction. Furthermore, petrosiol A ( 1 ) suppressed PDGF-induced actin filament dissociation and cell migration, suggesting that 1 and its derivatives may be used for the prevention and treatment of vascular diseases.

This study examined the effects of fargesin, a neolignan isolated from Magnolia plants, on obesity and insulin resistance and the possible mechanisms involved in these effects in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. Fargesin promoted the glucose uptake in 3T3-L1 adipocytes. In HFD-induced obese mice, fargesin decreased the body weight gain, white adipose tissue (WAT), and plasma triglyceride, non-esterified fatty acid and glucose levels, and improved the glucose tolerance. Fargesin increased glucose transporter 4 (GLUT4) protein expression and phosphorylation of Akt, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC) in both 3T3-L1 adipocytes and WAT of HFD-induced obese mice. Fargesin also decreased the mRNA expression levels of fatty acid oxidation-related genes, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1 (CPT-1), uncoupling protein-2 (UCP-2) and leptin in WAT. Taken together, the present findings suggest that fargesin improves dyslipidemia and hyperglycemia by activating Akt and AMPK in WAT. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Nobiletin (NOB) is a polymethoxylated flavone present in citrus fruits and has been reported to have antitumor and anti-inflammatory effects. However, little is known about the effects of NOB on obesity and insulin resistance. In this study, we examined the effects of NOB on obesity and insulin resistance, and the underlying mechanisms, in high-fat diet (HFD)-induced obese mice. Obese mice were fed a HFD for 8 weeks and then treated without (HFD control group) or with NOB at 10 or 100mg/kg. NOB decreased body weight gain, white adipose tissue (WAT) weight and plasma triglyceride. Plasma glucose levels tended to decrease compared with the HFD group and improved plasma adiponectin levels and glucose tolerance. Furthermore, NOB altered the expression levels of several lipid metabolism-related and adipokine genes. NOB increased the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, fatty acid synthase, stearoyl-CoA desaturase-1, PPAR-α, carnitine palmitoyltransferase-1, uncoupling protein-2 and adiponectin, and decreased the mRNA expression of tumor necrosis factor-α and monocyte chemoattractant protein-1 in WAT. NOB also up-regulated glucose transporter-4 protein expression and Akt phosphorylation and suppressed IκBα degradation in WAT. Taken together, these results suggest that NOB improves adiposity, dyslipidemia, hyperglycemia and insulin resistance. These effects may be elicited by regulating the expression of lipid metabolism-related and adipokine genes, and by regulating the expression of inflammatory makers and activity of the insulin signaling pathway.

Platelet-derived growth factor (PDGF)-BB can induce abnormal proliferation and migration of vascular smooth muscle cells (VSMC) that are involved in the development of CVD. In our preliminary study, phytoalexin glyceollins (glyceollins I, II and III) isolated from soyabean seeds cultured withAspergillus sojaeshowed strong antioxidant and anti-inflammatory activity. Since antioxidants showed beneficial effects on chronic inflammatory diseases, the purpose of the present study was to examine the effects of glyceollins on PDGF-induced proliferation and migration in human aortic smooth muscle cells (HASMC). Incubation of resting HASMC with glyceollins for 24 h significantly diminished PDGF-increased cell number and DNA synthesis in a dose-dependent manner without any cytotoxicity. In addition to blocking of the PDGF-inducible progression through the G0/G1to the S phase of the cell cycle, glyceollins down-regulated the expression of cyclin-dependent kinase (CDK)2 and cyclin D1, and up-regulated the expression of CDK inhibitors such as p27kip1and p53.Glyceollins also effectively inhibited reactive oxygen species generation and phosphorylation of PDGF receptor-β, phospholipase Cγ1, Akt and extracellular signal-regulated kinase 1/2 by PDGF stimulation. Furthermore, glyceollins were found to inhibit PDGF-induced dissociation of actin filaments and cell migration. Thus, the results suggest that glyceollins could become a potent therapeutic agent for regulating VSMC-associated vascular disease such as atherosclerosis and restenosis after angioplasty.