Anti-Obesity Effects of GABA in C57BL/6J Mice with High-Fat Diet-Induced Obesity and 3T3-L1 Adipocytes.

Obesity is the excessive accumulation of body fat resulting from impairment in energy balance mechanisms. In this study, we aimed to investigate the mechanism whereby GABA (γ-aminobutyric acid) prevents high-fat diet-induced obesity, and whether it induces lipolysis and browning in white adipose tissue (WAT), using high-fat diet (HFD)-fed obese mice and 3T3-L1 adipocytes. We demonstrated that GABA substantially inhibits the body mass gain of mice by suppressing adipogenesis and lipogenesis. Consistent with this result, histological analysis of WAT demonstrated that GABA decreases adipocyte size. Moreover, we show that GABA administration decreases fasting blood glucose and improves serum lipid profiles and hepatic lipogenesis in HFD-fed obese mice. Furthermore, Western blot and immunofluorescence analyses showed that GABA activates protein kinase A (PKA) signaling pathways that increase lipolysis and promote uncoupling protein 1 (UCP1)-mediated WAT browning. Overall, these results suggest that GABA exerts an anti-obesity effect via the regulation of lipid metabolism.

In-Depth Understanding of Ecklonia stolonifera Okamura: A Review of Its Bioactivities and Bioactive Compounds.

Ecklonia stolonifera Okamura (ES) is mainly distributed in the coastal areas of the middle Pacific, around Korea and Japan, and has a long-standing edible value. It is rich in various compounds, such as polysaccharides, fatty acids, alginic acid, fucoxanthin, and phlorotannins, among which the polyphenol compound phlorotannins are the main active ingredients. Studies have shown that the extracts and active components of ES exhibit anti-cancer, antioxidant, anti-obesity, anti-diabetic, antibacterial, cardioprotective, immunomodulatory, and other pharmacological properties in vivo and in vitro. Although ES contains a variety of bioactive compounds, it is not widely known and has not been extensively studied. Based on its potential health benefits, it is expected to play an important role in improving the nutritional value of food both economically and medically. Therefore, ES needs to be better understood and developed so that it can be utilized in the development and application of marine medicines, functional foods, bioactive substances, and in many other fields. This review provides a comprehensive overview of the bioactivities and bioactive compounds of ES to promote in-depth research and a reference for the comprehensive utilization of ES in the future.

Gomisin N from Schisandra chinensis Ameliorates Lipid Accumulation and Induces a Brown Fat-Like Phenotype through AMP-Activated Protein Kinase in 3T3-L1 Adipocytes.

Obesity results from an imbalance between energy intake and energy expenditure, in which excess fat is stored as triglycerides (TGs) in white adipocytes. Recent studies have explored the anti-obesity effects of certain edible phytochemicals, which suppress TG accumulation and stimulate a brown adipocyte-like phenotype in white adipocytes. Gomisin N (GN) is an important bioactive component of Schisandra chinensis, a woody plant endemic to Asia. GN has antioxidant, anti-inflammatory and hepatoprotective effects in vivo and in vitro. However, the anti-obesity effects of GN in lipid metabolism and adipocyte browning have not yet been investigated. In the present study, we aimed to determine whether GN suppresses lipid accumulation and regulates energy metabolism, potentially via AMP-activated protein kinase (AMPK), in 3T3-L1 adipocytes. Our findings demonstrate that GN inhibited adipogenesis and lipogenesis in adipocyte differentiation. Also, GN not only increased the expression of thermogenic factors, including uncoupling protein 1 (UCP1), but also enhanced fatty acid oxidation (FAO) in 3T3-L1 cells. Therefore, GN may have a therapeutic benefit as a promising natural agent to combat obesity.

Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation Through LPA Receptor.

Heat stress can be caused by various environmental factors. When exposed to heat stress, oxidative stress and inflammatory reaction occur due to an increase of reactive oxygen species (ROS) in the body. In particular, inflammatory responses induced by heat stress are common in muscle cells, which are the most exposed to heat stress and directly affected. Gintonin-Enriched Fraction (GEF) is a non-saponin component of ginseng, a glycolipoprotein. It is known that it has excellent neuroprotective effects, therefore, we aimed to confirm the protective effect against heat stress by using GEF. C2C12 cells were exposed to high temperature stress for 1, 12 and 15 h, and the expression of signals was analyzed over time. Changes in the expression of the factors that were observed under heat stress were confirmed at the protein level. Exposure to heat stress increases phosphorylation of p38 and extracellular signal-regulated kinase (ERK) and increases expression of inflammatory factors such as NLRP3 inflammasome through lysophosphatidic acid (LPA) receptor. Activated inflammatory signals also increase the secretion of inflammatory cytokines such as interleukin 6 (IL-6) and interleukin 18 (IL-18). Also, expression of glutathione reductase (GR) and catalase related to oxidative stress is increased. However, it was confirmed that the changes due to the heat stress were suppressed by the GEF treatment. Therefore, we suggest that GEF helps to protect heat stress in muscle cell and prevent tissue damage by oxidative stress and inflammation.

The Role of Fucoidans Isolated from the Sporophylls of Undaria pinnatifida against Particulate-Matter-Induced Allergic Airway Inflammation: Evidence of the Attenuation of Oxidative Stress and Inflammatory Responses.

Ambient particulate matter (PM) is a critical environment pollutant that promotes the onset and aggravation of respiratory diseases such as asthma through airway inflammation and hypersecretion of mucus. In this study, we aimed to identify the effects of fucoidans isolated from sporophylls of Undaria pinnatifida on asthma symptoms such as the inflammatory response and mucus secretion using a mouse model. Balb/c mice, intraperitoneally sensitized with ovalbumin (OVA, 10 µg) dissolved in 200 µL saline and 2 mg Al(OH)3, were exposed to PM (5 mg/m3) for 7 consecutive days. In parallel, along with PM exposure, we orally administrated fucoidans (100, 400 mg/Kg) or prednisone (5 mg/Kg), an anti-inflammatory drug. We found that oral administration of fucoidans significantly attenuated PM-induced lipid peroxidation and infiltration of inflammatory cells like F4/80+ macrophages, Gr-1+ granulocytes, and CD4+ T lymphocytes. Fucoidans also attenuated the level of PM-exacerbated IL-4, a primitive cytokine released in Th2 mediated eosinophilic asthma. This further suppressed mast cell activation, degranulation and IgE synthesis of PM exposed mice. Interestingly, fucoidans attenuated PM-exacerbated mucus hypersecretion and goblet cell hyperplasia. Therefore, our results suggest that fucoidans are effective at alleviating PM-exacerbated allergic asthma symptoms by attenuating the airway inflammatory response and mucus hypersecretion.

Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an Aß1-40-injected mouse model of Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) is associated with an increased inflammatory response via activated microglia and astrocytes. In the present study, we investigated whether treatment with the anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody adalimumab can improve cognitive function and reduce AD pathology in Aß1-40-injected animal models of AD, as well as the mechanisms underlying the effects of treatment. Aß1-40-injected mice treated with adalimumab exhibited significant improvements in memory relative to mice injected with Aß1-40 alone, as well as decreases in beta secretase-1 (BACE1) protein expression and Aß1-40 plaques. In addition, adalimumab treatment significantly attenuated neuronal damage and neuroinflammation in Aß1-40-injected mice. Aß1-40-induced decreases in brain-derived neurotrophic factor (BDNF) expression were also attenuated by treatment with adalimumab. Our experiments further verified that the effects of adalimumab are mediated by nuclear factor kappa B (NF-κB) p65 signalling. Serine 536 residues of NF-κB p65, which is phosphorylated by TNF-α, increased along with the degradation of inhibitor of κB (IκB) in the hippocampus of Aß-injected mice, although these effects were again attenuated by adalimumab. Furthermore, Aß1-40-induced increases in TNF-α and interleukin (IL)-6 expression were decreased by treatment with adalimumab. Our results indicate that adalimumab may be clinically useful in human patients with AD.

Ishige okamurae Extract Ameliorates the Hyperglycemia and Body Weight Gain of db/db Mice through Regulation of the PI3K/Akt Pathway and Thermogenic Factors by FGF21.

Type 2 diabetes mellitus and related metabolic disorders, such as dyslipidemia, present increasing challenges to health worldwide, as a result of urbanization, the increasing prevalence of obesity, poor lifestyle, and other stress-related factors. Ishige okamurae extract (IOE) is known to be effective at lowering blood glucose and ameliorating metabolic disease. However, detailed mechanisms for these effects have yet to be elucidated. Here, we show that IOE ameliorates substrate (IRS)/ phosphatidylinositol 3-kinase (PI3K)/Akt pathway and increasing glucose transporter 4 (GLUT4) expression in skeletal muscle and white adipose tissue (WAT). We also demonstrate that IOE increases the expression of fibroblast growth factor (FGF)21, a regulator of glucose and energy metabolism in muscle and WAT. In addition, IOE administration increased peroxisome proliferator-activated receptor γ coactivator 1α expression, which regulates expression of the key thermogenic molecule uncoupling protein 1 in WAT. Thus, the effects of IOE to ameliorate hyperglycemia and adiposity may be mediated through FGF21 activating insulin signaling and increasing the expression of GLUT4 and pro-thermogenic factors.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

6-Gingerol Suppresses Adipocyte-Derived Mediators of Inflammation In Vitro and in High-Fat Diet-Induced Obese Zebra Fish.

The present study was performed to investigate the molecular mechanism of 6-gingerol on adipocyte-mediated systemic inflammation in vitro and in high-fat diet-induced obese zebra fish. 6-Gingerol decreased adipogenesis due to the suppression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor gamma, CCAATT enhancer binding protein α, and adipocyte protein 2, and triglyceride synthesis enzymes, including sterol regulatory element-binding protein-1, fatty acid synthase, lysophosphatidic acid acyltransferase, and acyl-coA : diacylglycerol acyltransferase 1, in 3T3-L1. A coculture insert system using 3T3-L1 with RAW 264.7 (coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages) revealed that 6-gingerol increased anti-inflammatory cytokine interleukin-10. The expression of TNFα, monocyte chemotactic protein-1, interleukin-1ß, and interleukin-6 were decreased in the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages treated with 6-gingerol. Moreover, the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages treated with 6-gingerol inhibited the protein expression of TNFα and monocyte chemotactic protein-1 in RAW 264.7. 6-Gingerol decreased c-JUN N-terminal kinase and I kappa B kinase beta and its downstream target AP-1 expression in the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages. Furthermore, 6-gingerol decreased the expression of inducible nitric oxide synthase stimulated by the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages in RAW 264.7 and attenuated nitric oxide production in diet-induced obese zebra fish. Our results suggest that 6-gingerol suppresses inflammation through the regulation of the c-JUN N-terminal kinase-I kappa B kinase beta and its downstream targets.

Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3ß Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-ß 1-42 in Mice.

Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-ß 1-42 (Aß1-42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aß1-42 in mice. SM70EE increased the step-through latency time in the passive avoidance test and decreased the escape latency time in the Morris water maze test in Aß1-42-injected mice. SM70EE reduced hippocampal Aß1-42 levels and inhibited amyloid precursor protein processing-associated factors in Aß1-42-injected mice. Additionally, acetylcholinesterase activity was suppressed by SM70EE in Aß1-42-injected mice. Hippocampal glutathione levels were examined to determine the effects of SM70EE on oxidative stress in Aß1-42-injected mice. SM70EE increased the levels of glutathione and its associated factors that were reduced in Aß1-42-injected mice. SM70EE also promoted activation of the brain-derived neurotrophic factor/phosphatidylinositol-3 kinase/serine/threonine protein kinase signaling pathway and inhibited glycogen synthase kinase-3ß phosphorylation. These findings suggested that SM70EE ameliorated Aß1-42-induced cognitive impairments by inhibiting the increased phosphorylation of glycogen synthase kinase-3ß caused by intracerebroventricular injection of Aß1-42 in mice.

Crude Ecklonia cava Flake Extracts Attenuate Inflammation through the Regulation of TLR4 Signaling Pathway in LPS-Induced RAW264.7 Cells.

We investigated the beneficial effects of the crude Ecklonia cava flake (CEF), which is a residual product after polyphenol extraction from Ecklonia cava, on inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF extracts was obtained by a preparation process using water, hydrochloric acid or temperature. We observed that large-size (>19 kDa) CEF extract, which was extracted with water at 95 °C (CEF-W, 95 °C), suppressed the production of inflammatory cytokines by inhibiting its mRNA expression in LPS-induced RAW264.7 cells. TLR4 signaling involvements were negatively regulated by CEF-W, 95 °C. CEF-W, 95 °C repressed the translocation of NF-κB from cytoplasm into nucleus in LPS-induced RAW264.7 cells. CEF-W, 95 °C attenuated the phosphorylation of TBK1 and IRF3 by inhibiting the phosphorylation of ERK. Taken together, we demonstrated that large-size CEF-W, 95 °C may act as a negative regulator of inflammation through the suppression of TLR4 signaling constituents in LPS-induced RAW264.7 cells.

Modulation of HO-1 by Ferulic Acid Attenuates Adipocyte Differentiation in 3T3-L1 Cells.

Ferulic acid (FA) is phenolic compound found in fruits. Many studies have reported that FA has diverse therapeutic effects against metabolic diseases. However, the mechanism by which FA modulates adipogenesis via the expression of heme oxygenase-1 (HO-1) implicated in suppression of adipocyte differentiation is not fully understood. We investigated whether HO-1 can be activated by FA and suppress adipogenic factors in 3T3-L1. Our results showed that FA suppresses triglyceride-synthesizing enzymes, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). We observed that the expression of CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) were suppressed by FA. In addition, HO-1 inhibitor stimulated lipid accumulation, while FA attenuated lipid accumulation in 3T3-L1 treated with HO-1 inhibitor. We also observed that the expression of HO-1 had the same tendency as C/EBP homologous protein 10 (CHOP10) during the mitotic clonal expansion (MCE) of adipogenesis. We next employed siRNA against HO-1 to clarify whether HO-1 regulates CHOP10. The results indicated that CHOP10 is downstream of HO-1. Furthermore, FA-mediated HO-1/CHOP10 axis activation prevented the initiation of MCE. Therefore, we demonstrated that FA is a positive regulator of HO-1 in 3T3-L1, and may be an effective bioactive compound to reduce adipocyte tissue mass.

Spirulina maxima Extract Prevents Neurotoxicity via Promoting Activation of BDNF/CREB Signaling Pathways in Neuronal Cells and Mice.

Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin (TMT)-induced neurotoxicity in HT-22 cells. SM70EE inhibited the cleavage of poly-ADP ribose polymerase (PARP). Besides, ROS production was decreased by down-regulating oxidative stress-associated enzymes. SM70EE increased the factors of brain-derived neurotrophic factor (BDNF)/cyclic AMPresponsive elementbinding protein (CREB) signalling pathways. Additionally, acetylcholinesterase (AChE) was suppressed by SM70EE. Furthermore, we investigated whether SM70EE prevents cognitive deficits against scopolamine-induced neurotoxicity in mice by applying behavioral tests. SM70EE increased step-through latency time and decreased the escape latency time. Therefore, our data suggest that SM70EE may prevent TMT neurotoxicity through promoting activation of BDNF/CREB neuroprotective signaling pathways in neuronal cells. In vivo study, SM70EE would prevent cognitive deficits against scopolamine-induced neurotoxicity in mice.

Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats.

Fucoxanthin Suppresses Lipid Accumulation and ROS Production During Differentiation in 3T3-L1 Adipocytes.

Fucoxanthin, a pigment from the chloroplasts of marine brown algae, has a number of effects against obesity, diabetes, inflammation and cancer and provides cerebrovascular protection. In this study, we investigated the inhibitory effects of fucoxanthin on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis. Treatment with fucoxanthin suppresses protein levels of the adipogenic transcription factors CCAAT/enhancer-binding protein alpha C/EBPα and peroxisome proliferator-activated receptor-γ and of their target protein, fatty acid binding protein 4. Lipogenesis-related enzymes, such as diglyceride acyltransferase 1 and lysophosphatidic acid acyltransferase-θ, were downregulated by fucoxanthin. The ROS-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and the NADPH-generating enzyme glucose-6-phosphate dehydrogenase also decreased following fucoxanthin treatment. The adipokine adiponectin and the ROS-scavenging enzymes superoxide dismutase 2, glutathione reductase and catalase were dose-dependently increased by fucoxanthin. Furthermore, lipolysis-related enzymes and superoxide dismutase 1 were slightly decreased, because of the suppression of lipid-generating factors and the cytosolic enzyme NOX4. To confirm these results, we investigated lipid accumulation and ROS production in zebrafish, where fucoxanthin suppressed lipid and triglyceride accumulation, as well as ROS production. Our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic and lipogenic factors and ROS-regulating enzymes. Copyright © 2016 John Wiley & Sons, Ltd.

Acute and subchronic (28 days) oral toxicity studies of Codonopsis lanceolata extract in Sprague-Dawley rats.

Codonopsis lanceolata is a perennial plant that has been used as a food and in traditional medicine for the treatment of cough, bronchitis, and inflammation in East Asia including Korea, Japan, and China. However, information regarding its toxicity is limited. Therefore, we performed a safety evaluation of aqueous C. lanceolata root extract (CLE) in Sprague-Dawley rats. Assessment of acute toxicity revealed that CLE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 5000 mg/kg body weight. In the subchronic oral toxicity, data revealed that several significant alteration in food consumption, water consumption, protein excretion, WBCs levels, TGs, BUN levels, and the absolute and relative weights in the liver, spleen and lungs. However, these changes were transient and were not considered treatment related because they showed no apparent dose dependent. These results suggest that CLE (1250, 2500, and 5000 mg/kg body weight/day) administered orally does not cause acute or subchronic toxicity to male or female rats. The 50% lethal dose (LD50) of CLE was determined to be greater than 5000 mg/kg.

Ellagic acid suppresses lipid accumulation by suppressing early adipogenic events and cell cycle arrest.

Ellagic acid (EA) is a natural polyphenol found in various fruits and vegetables. In this study, we examined the inhibitory effect of EA on fat accumulation in 3T3-L1 cells during adipogenesis. Our data showed that EA reduced fat accumulation by down-regulating adipogenic markers such as peroxisome proliferator activated receptor γ (PPARγ) and the CCAAT/enhancer binding protein α (C/EBPα) at the mRNA and protein levels in a dose-dependent manner. We found that the decrease in adipogenic markers resulted from reduced expression of some early adipogenic transcription factors such as KLF4, KLF5, Krox20, and C/EBPß within 24 h. Also, these inhibitions were correlated with down-regulation of TG synthetic enzymes, causing inhibition of triglyceride (TG) levels in 3T3-L1 cells investigated by ORO staining and in zebrafish investigated by TG assay. Additionally, the cell cycle analysis showed that EA inhibited cell cycle progression by arresting cells at the G0/G1 phase.

Brazilein Suppresses Inflammation through Inactivation of IRAK4-NF-κB Pathway in LPS-Induced Raw264.7 Macrophage Cells.

The medicinal herbal plant has been commonly used for prevention and intervention of disease and health promotions worldwide. Brazilein is a bioactive compound extracted from Caesalpinia sappan Linn. Several studies have showed that brazilein exhibited the immune suppressive effect and anti-oxidative function. However, the molecular targets of brazilein for inflammation prevention have remained elusive. Here, we investigated the mechanism underlying the inhibitory effect of brazilein on LPS-induced inflammatory response in Raw264.7 macrophage cells. We demonstrated that brazilein decreased the expression of IRAK4 protein led to the suppression of MAPK signaling and IKKß, and subsequent inactivation of NF-κB and COX2 thus promoting the expression of the downstream target pro-inflammatory cytokines such as IL-1ß, MCP-1, MIP-2, and IL-6 in LPS-induced Raw264.7 macrophage cells. Moreover, we observed that brazilein reduced the production of nitrite compared to the control in LPS-induced Raw264.7. Thus, we suggest that brazilein might be a useful bioactive compound for the prevention of IRAK-NF-κB pathway associated chronic diseases.

Role of the Red Ginseng in Defense against the Environmental Heat Stress in Sprague Dawley Rats.

Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the effect of RG on heat stress, we examined the effect of the RG on the gene expression profiles in rats subjected to environmental heat stress. We evaluated the transcripts associated with hepatic lipid accumulation and oxidative stress in rats subjected to heat stress. We also analyzed the reactive oxygen species (ROS) contents. Our results suggested RG inhibited heat stress mediated altering mRNA expressions include HSPA1, DEAF1, HMGCR, and FMO1. We also determined RG attenuated fat accumulation in the liver by altering C/EBPß expression. RG promoted to repress the heat stress mediated hepatic cell death by inhibiting of Bcl-2 expression in rats subjected to heat stress. Moreover, RG administered group during heat stress dramatically decreased the malondialdehyde (MDA) contents and ROS associated genes compared with the control group. Thus, we suggest that RG might influence inhibitory effect on environmental heat stress induced abnormal conditions in humans.

Seapolynol Extracted from Ecklonia cava Inhibits Adipocyte Differentiation in Vitro and Decreases Fat Accumulation in Vivo.

Seapolynol (SN) is a polyphenol mixture derived from Ecklonia cava. We evaluated the effects of SN on lipid accumulation in adipocytes, zebrafish, and mice. SN effectively inhibited lipid accumulation in three experimental models by suppressing adipogenic factors. Triglyceride synthetic enzymes such as diacylglycerol acyltransferase 1 (DGAT1) and GPAT3 were also downregulated by SN. This SN-induced inhibition of adipogenic factors was shown to be due to the regulatory effect of SN on early adipogenic factors; SN downregulated the expression of Krueppel-like factor 4 (KLF4), KLF5, CCAAT-enhancer-binding protein ß (C/EBPß), C/EBPδ, and Protein C-ets-2 (ETS2), while KLF2, an anti-early adipogenic factor, was upregulated by SN. SN-mediated inhibition in early adipogenesis was closely correlated with the inhibition of mitotic clonal expansion via cell cycle arrest. SN inhibited cell cycle progression by suppressing cell cycle regulators, such as cyclin A, cyclinD, and pRb but increased p27, a cell cycle inhibitor. In a mouse study, SN effectively reduced body weight and plasma lipid increases induced by a high-fat diet; triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels were markedly reduced by SN. Moreover, SN remarkably improved high-fat-diet-induced hepatic lipid accumulation. Furthermore, SN activated AMP-activated protein kinase-α (AMPKα), an energy sensor, to suppress acetyl-coA carboxylase (ACC), inhibiting lipid synthesis. Our study suggests that SN may be an edible agent that can play a positive role in prevention of metabolic disorders.