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Chronic kidney disease (CKD) is a progressive loss of kidney function associated with inflammation and fibrosis. Chrysanthemum coronarium L. (CC), a leafy vegetable, possesses various beneficial properties, including anti-oxidative, anti-inflammatory, and antiproliferative effects. This study aimed to determine the renoprotective effects of CC on adenine-induced CKD in mice. CKD was induced by feeding mice an adenine diet (0.25% w/w) for 4 weeks. Changes in renal function, histopathology, inflammation, and renal interstitial fibrosis were analyzed. The adenine-fed mice were characterized by increased blood urea nitrogen, serum creatinine, and histological changes, including inflammation and fibrosis; however, these changes were significantly restored on treatment with CC. Additionally, CC inhibited the expression of inflammatory markers, monocyte chemoattractant protein-1, interleukins-6 and − 1β, intercellular adhesion molecule-1, and cyclooxygenase 2. Moreover, CC suppressed the expression of the fibrotic markers, type IV collagen, and fibronectin. Furthermore, CC attenuated the expression of profibrotic genes (tumor growth factor-β and α- smooth muscle actin) in adenine-induced renal injury mice. These results suggest that CC has the potential to attenuate adenine-induced renal injury and might offer a new option as a renoprotective agent or functional food supplement for moderate CKD.

BackgroundHansik, a traditional Korean diet, may have a beneficial impact on metabolic syndrome (MetS) risk as dietary westernization increases its prevalence. We examined the hypothesis that adherence to the hansik diet may be inversely associated with the risk of MetS and its components and sought to understand the gender differences in 58,701 men and women aged over 40.Materials and methodsHansik was defined using 14 components from which the Korean dietary pattern index (Kdiet-index) was generated by summing their scores. Low-hansik intake was defined as the Kdiet-index with ResultsThe Kdiet-index score was negatively associated with the dietary inflammation index and showed that the high intake of a meal with multigrain rice, fruits, and their products, and nuts, and low intake of fried foods were inversely associated with MetS by 0.707, 0.864, 0.769, and 0.918 times, respectively, after adjusting for covariates. More women and participants with more educated and lower income belonged to the high-hansik group, and participants with high self-rated health scores consumed more hansik. All participants on a high-hansik diet were associated with a 0.87 time lower risk of MetS. Specifically, the association between hansik intake and MetS risk was not significant among men following stratification by gender. Body composition, including the body mass index, waist circumference, and fat mass, was inversely associated with hansik intake, while the skeletal muscle mass index was positively associated with the hansik intake in each gender and all participants. In all the participants in the high-hansik group, no significant changes were seen in the serum glucose and HDL concentration. However, a high-hansik intake showed lower blood pressure and serum LDL and triglyceride concentrations only in men and a higher glomerular filtration rate in both genders.ConclusionsHansik intake might improve MetS risk, with its primary beneficial effects on body composition, dyslipidemia, and blood pressure gender-dependently.

Over the last several decades, there has been a considerable growth in type 2 diabetes (T2DM) in Asians. A pathophysiological mechanism in Asian T2DM is closely linked to low insulin secretion, β-cell mass, and inability to compensate for insulin resistance. We hypothesized that genetic variants associated with lower β-cell mass and function and their combination with unhealthy lifestyle factors significantly raise T2DM risk among Asians. This hypothesis was explored with participants aged over 40. Participants were categorized into T2DM (case; n = 5383) and control (n = 53,318) groups. The genetic variants associated with a higher risk of T2DM were selected from a genome-wide association study in a city hospital-based cohort, and they were confirmed with a replicate study in Ansan/Ansung plus rural cohorts. The interacted genetic variants were identified with generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS)-nutrient interactions were examined. The 8-SNP model was positively associated with T2DM risk by about 10 times, exhibiting a higher association than the 20-SNP model, including all T2DM-linked SNPs with p < 5 × 10−6. The SNPs in the models were primarily involved in pancreatic β-cell growth and survival. The PRS of the 8-SNP model interacted with three lifestyle factors: energy intake based on the estimated energy requirement (EER), Western-style diet (WSD), and smoking status. Fasting serum glucose concentrations were much higher in the participants with High-PRS in rather low EER intake and high-WSD compared to the High-EER and Low-WSD, respectively. They were shown to be higher in the participants with High-PRS in smokers than in non-smokers. In conclusion, the genetic impact of T2DM risk was mainly involved with regulating pancreatic β-cell mass and function, and the PRS interacted with lifestyles. These results highlight the interaction between genetic impacts and lifestyles in precision nutrition.

Type 2 diabetes (T2DM) has markedly increased among Asians as their diets and lifestyles become more westernized. We, therefore, investigated the hypothesis that the Korean healthy eating index (KHEI) scores are associated with gender-specific T2DM risk in adults. The hypothesis was tested using the data from the Korea National Health and Nutrition Examination Survey-VI (2013–2017) with a complex sample survey design. Along with the KHEI scores, the modified KHEI (MKHEI) scores for the Korean- (KSD) and Western-style diets (WSD) were used as independent parameters, calculated using a validated semi-quantitative food-frequency questionnaire (SQFFQ). We estimated the association between the KHEI or MKHEI and the T2DM risk using logistic regression after adjusting for T2DM-related covariates. The adults with T2DM were more frequently older men who were less educated, married, on a lower income, and living in rural areas compared to those without T2DM. Not only the fasting serum glucose concentrations but also the waist circumferences and serum triglyceride concentrations were much higher in adults with T2DM than in those without T2DM in both genders. Serum HDL concentrations in the non-T2DM subjects exhibited a greater inverse relationship to serum glucose than in the T2DM group in both genders. Twenty-four-hour recall data revealed that women, but not men, had higher calcium, vitamin C, saturated and monounsaturated fatty acids, retinol, and vitamin B2 intakes than the T2DM group. Furthermore, overall, the KHEI score and the adequacy and balance scores among its components were significantly higher in the non-T2DM group than in the T2DM group, but only in women. The KHEI scores were inversely associated with T2DM only in women. The mixed grain intake score was higher in the non-T2DM than the T2DM group only in men. However, there were no differences between the groups in the MKHEI scores for KSD and WSD. In conclusion, high KHEI scores in the adequacy and balance components might prevent and/or delay T2DM risk, but only in women.

Generalized healthy eating patterns may not benefit everyone due to different genetics and enterotypes. We aimed to compare the effects of a low-glycemic diet representing the Korean traditional balanced diet (Low-GID) and westernized diet as a control diet (CD) on anthropometry, serum metabolites, and fecal bacteria in a randomized clinical trial according to enterotypes. We recruited 52 obese women aged 30–50 years, and they consumed Low-GID and CD meals for 1 month, with a 1-month washout period, in a crossover randomized clinical trial. The Low-GID was mainly composed of whole grains with fish, vegetables, seaweeds, and perilla oil, whereas CD contained refined rice, bread, noodles, meats, and processed foods. Serum lipid profiles, metabolomics, serum short-chain fatty acids, and fecal bacteria were analyzed. The important variables influenced by Low-GID and CD were determined by SHAP value in the XGBoost algorithm according to Bacteroides (ET-B) and Prevotella (ET-P). Low-GID and CD interventions did not change the enterotypes, but they modified serum metabolites and some fecal bacterial species differently according to enterotypes. The 10-fold cross-validation of the XGBoost classifier in the ET-P and ET-B clusters was 0.91 ± 0.04 and 0.8 ± 0.07, respectively. In the ET-P cluster, serum L-homocysteine, glutamate, leucine concentrations, and muscle mass were higher in the CD group than in the Low-GID group, whereas serum 3-hydroxybutyric acid concentration was significantly higher in the Low-GID group than in the CD group (p < 0.05). In fecal bacteria, Gemmiger formicilis, Collinsella aerofaciens, and Escherichia coli were higher in the CD group than in the Low-GID group. In the ET-B cohort, serum tryptophan and total cholesterol concentrations were higher in the CD group than in the Low-GID group, whereas serum glutathione and 3-hydroxybutyric acid concentrations were significantly higher in the Low-GID group than in the CD group (p < 0.05). However, Bifidobacterium longum was higher in CD than Low-GID in the ET-B cluster, but serum butyric acid levels were higher in the Low-GID than in the CD group. In conclusion, Low-GID can be recommended in obese women with both ET-P and ET-B enterotypes, although its efficacy was more effective in ET-P.Clinical Trial Registration[https://cris.nih.go.kr/cris/search/detailSearch.do/17398], identifier [KCT0005340].

Bone homeostasis is dynamically balanced between bone forming osteoblasts and bone resorbing osteoclasts. Osteoclasts play an important role in bone destruction and osteoporosis, and they are derived from monocyte/macrophages in response to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). Amaranthus mangostanus L. (AM) is a plant with powerful antioxidant and other biological activities including anti-inflammatory, antidiabetic, and antihyperlipidemic effects. However, its effects on bone health are unknown. In this study, we explored whether AM could affect RANK-mediated osteoclastogenesis. AM significantly suppressed RANKL-induced osteoclast differentiation and expression of osteoclast-specific genes, TRAP, cathepsin K, NF-activated T-cells (NFATc1), and Dc-stamp in RAW 264.7 cells. Moreover, AM significantly inhibited extracellular signal-regulated kinase (ERK), Akt, and NF-κB signaling pathways in RAW 264.7 cells. In addition, AM preserved ovariectomy-induced bone loss in mice. Taken together, our results suggest that AM might be a potential candidate for the treatment of postmenopausal osteoporosis.

Abdominal obesity is a critical factor for metabolic diseases, and specific eating patterns such as the Mediterranean diet help prevent metabolic diseases. This study aimed to investigate the association between the modified Korean health eating index (MKHEI), including a Korean-balanced diet, and abdominal obesity risk according to genders in adults aged 20–64 years (4,886 males and 7,431 females), using the Korea National Health and Nutrition Examination Survey VI (2013–2016). Adjusted means and 95% confidence intervals of MKHEI scores and nutrient intake estimated using the 24-h recall method were calculated according to abdominal obesity (waist circumference ≥90 cm for men and ≥85 cm for women) after adjusting for age, residence area, region, education, income, drinking status, smoking status, marital status, and exercise. Adjusted odds ratios (ORs) for abdominal obesity were measured according to MKHEI tertiles using logistic regression analysis while controlling for covariates. Individuals aged >50 years, married, below high school, lower-income, heavy alcohol drinkers, past and current smokers, and males living in the southern areas had a higher risk of abdominal obesity. In both genders, the scores of all MKHEI components were lower in the abdominal obesity group (n = 2,895) than in the control group (n = 9,422). Further, the scores of fruits with and without fruit juice and those of beans, including fermented beans, were lower in the abdominal obesity group only in females but not in males. Further, the scores of fast foods were higher in the abdominal obesity group than in the control group only in females. After adjusting for covariates, the adjusted OR for abdominal obesity was inversely associated with Korean balanced diet (KBD) related to KHEI scores. Unlike KBD, MKHEI of Western-style diet was not associated with abdominal obesity in either gender. In conclusion, KBD can lower the risk of abdominal obesity in females and should thus be recommended to prevent abdominal obesity.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30–40 years, who were randomly assigned to two groups—a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

Atherosclerosis manifests as a chronic inflammation resulting from multiple interactions between circulating factors and various cell types in blood vessel walls. Growing evidence shows that phenotypic switching and proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the progression of atherosclerosis. Soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids are mediated by vascular inflammation. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl]-urea (TPPU) is an sEH inhibitor. This study investigated the therapeutic effect of TPPU on atherosclerosis in vivo and homocysteine-induced vascular inflammation in vitro and explored their molecular mechanisms. We found that TPPU decreased WD-induced atherosclerotic plaque lesions, inflammation, expression of sEH, and nicotinamide adenine dinucleotide phosphate oxidase-4 (Nox4), and increased the expression of contractile phenotype marker of aortas in ApoE (-/-) mice. TPPU also inhibited homocysteine-stimulated VSMC proliferation, migration, and phenotypic switching, and reduced Nox4 in human-aorta-VSMC regulation. We conclude that TPPU has anti-atherosclerotic effects, potentially because of the suppression of VSMC phenotype switching. Thus, TPPU could be a potential therapeutic target for phenotypic switching attenuation in atherosclerosis.

Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women.

Osteoporosis is characterized by decreased bone mass and bone microarchitectural failure, leading to an enhanced risk of bone fractures. Chrysanthemum coronarium L. (CC) is a natural plant with powerful antioxidant activity. This study investigated the antiosteoporotic effects of CC extracts in in vitro cell cultures and in vivo bone loss animal models. CC stimulated osteoblast differentiation and mineralized bone formation by osteoblasts by increasing the expression of bone formation markers (alkaline phosphatase, osteoprotegerin, and osteoprotegerin/receptor activator nuclear factor-κB ligand ratio) in the murine preosteoblastic cell line MC3T3-E1. Additionally, CC was found to inhibit osteoclast differentiation by downregulating bone resorption markers (tartrate-resistant acid phosphatase, cathepsin K, dendritic cell-specific transmembrane protein, and calcitonin receptor) in the murine macrophage-like cell line RAW264.7. CC prevented ovariectomy-induced bone loss, preserved trabecular microarchitecture, and improved serum bone turnover markers in an osteoporotic mouse model. These findings suggest that CC extract may be considered as a natural therapeutic or preventive agent for osteoporotic bone loss.

Osteoporosis is characterized by decreased bone mass and bone microarchitectural failure, leading to an enhanced risk of bone fractures. Chrysanthemum coronarium L. (CC) is a natural plant with powerful antioxidant activity. This study investigated the antiosteoporotic effects of CC extracts in in vitro cell cultures and in vivo bone loss animal models. CC stimulated osteoblast differentiation and mineralized bone formation by osteoblasts by increasing the expression of bone formation markers (alkaline phosphatase, osteoprotegerin, and osteoprotegerin/receptor activator nuclear factor-κB ligand ratio) in the murine preosteoblastic cell line MC3T3-E1. Additionally, CC was found to inhibit osteoclast differentiation by downregulating bone resorption markers (tartrate-resistant acid phosphatase, cathepsin K, dendritic cell-specific transmembrane protein, and calcitonin receptor) in the murine macrophage-like cell line RAW264.7. CC prevented ovariectomy-induced bone loss, preserved trabecular microarchitecture, and improved serum bone turnover markers in an osteoporotic mouse model. These findings suggest that CC extract may be considered as a natural therapeutic or preventive agent for osteoporotic bone loss.

Obese Asians are more susceptible to metabolic diseases than obese Caucasians of the same body mass index (BMI). We hypothesized that the genetic variants associated with obesity risk interact with the lifestyles of middle-aged and elderly adults, possibly allowing the development of personalized interventions based on genotype. We aimed to examine this hypothesis in a large city hospital-based cohort in Korea. The participants with cancers, thyroid diseases, chronic kidney disease, or brain-related diseases were excluded. The participants were divided into case and control according to their BMI: ≥25 kg/m2 (case, n = 17,545) and &lt, 25 kg/m2 (control, n = 36,283). The genetic variants that affected obesity risk were selected using a genome-wide association study, and the genetic variants that interacted with each other were identified by generalized multifactor dimensionality reduction analysis. The selected genetic variants were confirmed in the Ansan/Ansung cohort, and polygenetic risk scores (PRS)−nutrient interactions for obesity risk were determined. A high BMI was associated with a high-fat mass (odds ratio (OR) = 20.71) and a high skeletal muscle-mass index (OR = 3.38). A high BMI was positively related to metabolic syndrome and its components, including lipid profiles, whereas the initial menstruation age was inversely associated with a high BMI (OR = 0.78). The best model with 5-SNPs included SEC16B_rs543874, DNAJC27_rs713586, BDNF_rs6265, MC4R_rs6567160, and GIPR_rs1444988703. The high PRS with the 5-SNP model was positively associated with an obesity risk of 1.629 (1.475–1.798) after adjusting for the covariates. The 5-SNP model interacted with the initial menstruation age, fried foods, and plant-based diet for BMI risk. The participants with a high PRS also had a higher obesity risk when combined with early menarche, low plant-based diet, and a high fried-food intake than in participants with late menarche, high plant-based diet, and low fried-food intake. In conclusion, people with a high PRS and earlier menarche age are recommended to consume fewer fried foods and a more plant-based diet to decrease obesity risk. This result can be applied to personalized nutrition for preventing obesity.

The acetylation of histone and nonhistone proteins is associated with adipogenesis. The objective of the present study was to investigate whether an ethanol extract of Quercus acutissima fruit (QF) exhibits antiobesity effects through inhibition of acetylation in 3T3-L1 preadipocytes and high fat diet (HFD)-fed obese mice. We observed that QF acts as a histone acetyltransferase (HAT) inhibitor and that QF (400 μg/mL) markedly inhibits the activity of p300 and CREB-binding protein. QF (200 μg/mL) significantly attenuated lipid accumulation without apparent toxicity, which is likely attributable to a decrease in the expressions of lipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1, and CCAAT-enhancer-binding proteins alpha that were otherwise increased by MDI (a hormonal cocktail containing methyl isobutylmethylxanthine, dexamethasone, and insulin). MDI increased the acetylation of total lysine residues in whole 3T3-L1 cell lysate, an effect that was reversed by QF treatment (200 μg/mL). To further confirm the antiobesity activity of QF, mice were fed with HFD supplemented with QF at 50 and 200 mg/kg body weight. Mice fed with HFD exhibited increased masses of body, liver, and retroperitoneal fat, an effect that was suppressed in the presence of QF supplementation. QF-mediated decreases in body weight were attributable to a decrease in the average size of lipid droplets, as well as lipid accumulation in retroperitoneal fat and the liver, respectively. QF-mediated reductions in the size of the lipid droplets in the retroperitoneal fat tissue were likely associated with decreased expression of DGAT2. Taken together, our observations suggest that QF acts as an HAT inhibitor and attenuates adipogenesis in 3T3-L1 preadipocytes, resulting in the mitigation of HFD-induced obesity.

Histone lysine acetylation is thought to play a role in regulating the balance between energy storage and energy expenditure. However, the epigenetic mechanisms by which food phytochemicals influence metabolic processes in the liver have not been thoroughly investigated. In this study, we investigated the effect of an ethanol extract of Capsella bursa-pastoris (ECB) on histone acetyltransferase (HAT) inhibition, and whether it could thereby attenuate lipid accumulation in vitro and in vivo. We observed that ECB inhibits HAT activity as assessed by colorimetric and autoradiography assay systems. ECB also reduced oleic acid (OA)-stimulated histone acetylation at H4K5 and H4K12 and attenuated OA-mediated lipid accumulation in HepG2 cells, in the absence of observable cytotoxicity. We then investigated these effects in vivo. Mice were fed on either a normal diet (ND) or high-fat diet (HFD) in the presence or absence of ECB supplementation. In comparison with the ND controls, the HFD mice exhibited higher body weight, liver fat, adipose tissue size, and total serum cholesterol concentrations, and these effects were significantly attenuated by ECB supplementation. Taken together, these results suggest that ECB protects against the mechanisms responsible for HFD-induced hepatic steatosis, and may involve the targeting of histone H4K acetylation.

Saururus chinensis (SC), a traditional medicine, has been used for the treatment of edema, jaundice, gonorrhea, and several inflammatory diseases in China and Korea. Our previous studies reported the anti-osteoporotic activity of SC extract (SCE) in ovariectomized (OVX) rats but the mechanism of this effect was unclear. The aim of this study was to explore the anti-osteoporotic effect of SCE and elucidate the underlying mechanisms in ovariectomized rats using a metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF MS) to analyze metabolic changes. Female Sprague-Dawley (SD) rats were divided into sham, OVX, and SCE treatment groups. Partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots separated OVX and sham groups fairly well. Further, 22 potential biomarkers were identified in the rat models of estrogen deficiency-induced osteoporosis, and SCE showed regulatory effects on three vital metabolic pathways associated with these biomarkers, namely, glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, and linoleic acid metabolism. The metabolomics approach reliably confirmed that SCE exerted its anti-osteoporotic effect by intervening with lipid metabolism, thus preventing osteoporosis. This study also showed the promising potential of this approach in an evaluation of natural medicine efficacy.

Tangeretin is a natural flavone found mainly in citrus peels. Although emerging evidence suggests the beneficial health effects of tangeretin, little is known about the biological role of tangeretin in the odorant-induced signal transduction pathway. In this study, the effects of tangeretin on odorant-stimulated non-neuronal 3T3-L1 cells were evaluated. Here, we present the first evidence that an olfactory receptor for lyral, an odorant, is expressed in 3T3-L1 cells and that it responds to its ligand. Stimulation with lyral increased the cyclic adenosine monophosphate (cAMP) and Ca2+ levels as well as the phosphorylation of cAMP response element binding protein (CREB). Pretreatment with tangeretin synergistically enhanced the effects of stimulation with lyral: up-regulation of cAMP and Ca2+ levels and CREB phosphorylation. These data collectively suggest that tangeretin synergistically enhances the odorant-induced signaling pathway through modulation of cAMP and CREB signal transduction in non-chemosensory cells.

Hyperlipidemia is a risk factor for atherosclerotic cardiovascular disease and is a major public health concern. Allium hookeri (AH) is an Allium species containing high levels of bioactive organosulfur compounds such as methiin and cycloalliin. AH exerts hypolipidemic effects in animals fed a high-fat diet. However, there exists little information on the mechanisms underlying these effects. To address this issue, we used a metabolomic approach based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry to identify factors mediating the lipid-lowering effects of AH. Principal component and partial least-squares discriminant analyses of serum metabolome profiles revealed 25 metabolites as potential biomarkers for the effects of AH on lipid levels. These compounds were predominantly phospholipids, including phosphatidylcholines (PCs), lysoPCs, and lysophosphatidylethanolamines. Glycerophospholipid metabolism was identified as a significantly enriched pathway. These results provide mechanistic insight into the antihyperlipidemic effects of AH and evidence for its efficacy as a therapeutic agent.

The purpose of this study is to investigate the effects of euphorbiasteroid, a component of Euphorbia lathyris L., on adipogenesis of 3T3-L1 pre-adipocytes and its underlying mechanisms. Euphorbiasteroid decreased differentiation of 3T3-L1 cells via reduction of intracellular triglyceride (TG) accumulation at concentrations of 25 and 50 μM. In addition, euphorbiasteroid altered the key regulator proteins of adipogenesis in the early stage of adipocyte differentiation by increasing the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, levels of adipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α, were decreased by euphorbiasteroid treatment at the late stage of adipocyte differentiation. The anti-adipogenic effect of euphorbiasteroid may be derived from inhibition of early stage of adipocyte differentiation. Taken together, euphorbiasteroid inhibits adipogenesis of 3T3-L1 cells through activation of the AMPK pathway. Therefore, euphorbiasteroid and its source plant, E. lathyris L., could possibly be one of the fascinating anti-obesity agent. Copyright © 2015 John Wiley & Sons, Ltd.

Poly-γ-glutamic acid (PGA) is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK) in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study.

trans-Cinnamaldehyde (tCIN), an active compound found in cinnamon, is well known for its antioxidant, anticancer, and anti-inflammatory activities. The β-cyclodextrin (β-CD) oligomer has been used for a variety of applications in nanotechnology, including pharmaceutical and cosmetic applications. Here, we aimed to evaluate the anti-inflammatory and antioxidant effects of tCIN self-included in β-CD complexes (CIs) in lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophages. RAW 264.7 macrophages were treated with increasing concentrations of β-CD, tCIN, or CIs for different times. β-CD alone did not affect the production of nitric oxide (NO) or reactive oxygen species (ROS). However, both tCIN and CI significantly reduced NO and ROS production. Thus, CIs may have strong anti-inflammatory and antioxidant effects, similar to those of tCIN when used alone.

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)–connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2–Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2–Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJIC.

Polygonatum Officinalerhizome, a member of the liliaceae family, is commonly consumed as tea in Asia. It is also clinically used to treat obesity and fatigue in Korean traditional medicine. Although the anti-diabetic effect of POR has been described, little is known about its physiological role in the olfactory system. In this study, we investigated the effects of POR in 3T3-L1 cells expressing an odorant receptor. We have shown that the levels of cAMP and Ca2+ and the phosphorylation of Rap1A and CREB increased in response to an odorant, eugenol. POR significantly decreased the eugenol-induced increase in cAMP and Ca2+. Taken together, these data suggest that POR inhibits an odorant-induced signal transduction pathway.

Hepatic steatosis is the most common chronic liver disease in Western countries. Both genetic and environmental factors are known as causes of the disease although their underlying mechanisms have not been fully understood. This study investigated the association of DNA methylation with oleic acid-induced hepatic steatosis. It also examined effects of food components on DNA methylation in hepatic steatosis. Genome-wide DNA methylation of oleic acid (OA)-induced lipid accumulation in vitro cell model was investigated using reduced representation bisulfite sequencing. Changes of DNA methylation were also analyzed after treatment with food components decreasing OA-induced lipid accumulation in the model. We identified total 81 regions that were hypermethylated by OA but hypomethylated by food components or vice versa. We determined the expression of seven genes proximally located at the selected differentially methylated regions. Expression levels of WDR27, GNAS, DOK7, MCF2L, PRKG1, and CMYA5 were significantly different between control vs OA and OA vs treatment with food components. We demonstrated that DNA methylation was associated with expression of genes in the model of hepatic steatosis. We also found that food components reversely changed DNA methylation induced by OA and alleviated lipid accumulation. These results suggest that DNA methylation is one of the mechanisms causing the hepatic steatosis and its regulation by food components provides insights that may prevent or alleviate lipid accumulation.

In this study, we performed in vitro and in vivo studies to examine whether a 70% ethanol extract of Prunus mume fruits (EMS) exhibits anti-diabetic effects. Treatment with EMS increased glucose uptake in C2C12 myotubes, and also increased PPAR-γ activity or PPAR-γ mRNA expression. To confirm these in vitro results, we next conducted an animal experiment. A high-fat diet significantly increased the body weight, fat accumulation, and glucose levels in mice. Under the same conditions, 5% EMS attenuated the high-fat diet-induced increase in body weight and fat accumulation and improved the impaired fasting glucose level and glucose tolerance. High performance liquid chromatography analysis demonstrated that EMS contained chlorogenic acid, caffeic acid, rutin, luteolin-7-glucoside, naringin, apigenin-7-glucoside, and hesperidin. Taken together, these findings suggest that EMS exerts an anti-diabetic effect both in vitro and in vivo, which is mediated, at least in part, by the activation of PPAR-γ.

The antidiabetic effect of theCitrus junosTanaka (also known as yuja or yuzu) was examined. Ethanol extract of yuja peel (YPEE) significantly stimulated 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) uptake in C2C12 myotubes. However, ethanol extract of yuja pulp (YpEE) and water extract of yuja peel (YPWE) or pulp (YpWE) did not stimulate glucose uptake. In addition, peroxisome proliferator-activated receptor gamma (PPAR-γ) and AMP-activated protein kinase (AMPK) activities were increased by YPEE in a dose-dependent manner. Pretreatment of AMPK inhibitor decreased the glucose uptake stimulated by YPEE in C2C12 myotubes. We confirmed the anti-diabetic effect of YPEE in mice fed a high fat-diet (HFD). Compared with control mice on a normal diet (ND), these mice showed increased body weight, liver fat, insulin resistance, triacylglycerol (TG), and total cholesterol content. Addition of 5% YPEE significantly reduced the weight gain and rise in liver fat content, serum triacylglycerol (TG), total cholesterol, and insulin resistance found in mice fed a high-fat diet (HFD). Moreover, YPEE reduced the secretion of HFD-induced adipocytokines such as leptin and resistin. YPEE also resulted in increased phosphorylation of AMPK in muscle tissues. These results suggest that ethanol extract of yuja peel exerts anti-diabetic effects via AMPK and PPAR-γin both cell culture and mouse models.

In patients with inflammatory bowel disease (IBD), inflammation is induced and maintained by lymphangiogenesis and angiogenesis. 3,3'-Diindolylmethane (DIM) is a natural product formed in acidic conditions from indole-3-carbinol in cruciferous vegetables, and it is known for its chemotherapeutic activity. This study evaluated DIM's effects on angiogenesis, lymphangiogenesis, and inflammation in a mouse colitis model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water. DIM remarkably attenuated the clinical signs and histological characteristics in mice with DSS-induced colitis. DIM suppressed neutrophil infiltration and pro-inflammatory cytokines. Moreover, it significantly suppressed the expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR)-2, indicating that the mechanism may be related to the repression of pro-angiogenesis activity. DIM also remarkably suppressed the expression of VEGF-C, VEGF-D, VEGFR-3, and angiopoietin-2; thus, the mechanism may also be related to the suppression of lymphangiogenesis. Therefore, DIM is a possible treatment option for inflammation of the intestine and associated angiogenesis and lymphangiogenesis.

Recent studies suggest that phytoestrogens may exert a protective effect against osteoporosis. This study examined whether treatment with phytoestrogen extracts from Saururus chinensis (SC) exerted a preventive effect on estrogen-deficiency-induced osteoporosis. Six- to seven-month-old female Sprague–Dawley rats were randomly assigned into either a sham-operated group or one of three ovariectomy (OVX) subgroups: OVX treated with vehicle, OVX with alendronate, and OVX with SC extract (SC). Rats began receiving treatment 4weeks before the OVX treatment and continued receiving treatment for an additional 10weeks after OVX (for a combined total of 14weeks). The results showed that the SC treatment prevented loss of femur bone mineral density after OVX, as determined by a significant decrease in the levels of serum bone turnover markers osteocalcin and alkaline phosphatase as well as urinary deoxypyridinoline. Micro-computed tomography analysis showed that the SC treatment significantly prevented decreases in bone volume/tissue volume, trabecular number and trabecular thickness, while also preventing an increase in trabecular separation. It was concluded that SC treatment could prevent OVX-induced loss of bone mass and deterioration in trabecular microarchitecture by suppressing bone turnover, thereby maintaining bone structural integrity. Further, no stimulation of proliferation of uterine tissue was noted. Therefore, it is suggested that treatment with S. chinensis extracts might be a potential alternative therapy for treating postmenopausal osteoporosis. Copyright © 2012 John Wiley & Sons, Ltd.

Decursin (De), an active component of Angelica gigas, is known to exert anticancer and neuroprotective effects. However, its antiobesity and antidiabetic potential has not yet been investigated. This study evaluated the antiobesity effect of decursin, particularly focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. Decursin treatment resulted in the inhibition of adipocyte differentiation and the expression of fatty acid synthase. The study further investigated these antiobesity effects using mice fed a normal diet (ND), a high-fat diet (HFD) and a HFD plus decursin 200 mg/kg diet (HFD + De) for 7 weeks. Mice administered HFD plus decursin showed a drastic decrease in weight gain, triglyceride content, total cholesterol content and fat size compared with those that received the HFD alone; this was observed despite similar quantities of total food intake. Furthermore, decursin improved glucose tolerance in mice fed a HFD. Finally, administration of decursin along with the HFD significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1. These results suggest that decursin might be useful for the treatment of obesity and diabetes.

Liver and serum metabolites of obese and lean mice fed on high fat or normal diets were analyzed using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry, gas chromatography-mass spectrometry, and partial least-squares-discriminant analysis (PLS-DA). Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased β-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases. On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by chronic inflammation and joint destruction. In this study, we investigated whether dietary supplementation with alpha lipoic acid (ALA) suppresses collagen-induced arthritis (CIA) in mice. Mice were randomly divided into three groups: (1) a control CIA group was fed a normal diet, (2) a CIA group was fed a 0.1% ALA diet (average ALA intake of 160 mg/kg/day), and (3) a CIA group was fed a 0.5% ALA diet (average ALA intake of 800 mg/kg/day). The ALA-fed mice showed a decreased incidence and severity of arthritis compared to the normal diet group. Radiographic findings revealed a dramatic decrease in bone destruction, and histological findings showed extensively suppressed pathological changes in the ALA-fed mice. The ALA-fed mice exhibited inhibited generation of tartrate resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Additionally, ALA-fed mice reduced production of various proinflammatory cytokines and the soluble receptor activator of NF-κB ligand (sRANKL) in the joint tissues and the sera. In conclusion, dietary supplementation with ALA attenuated inflammatory responses and bone destruction in CIA mice.

Genistein is a polyphenolic nonsteroidal isoflavonoid with estrogen-like activity has been shown to have anticancer, antioxidant, and anti-inflammatory activities. Fractalkine is a unique chemokine that functions as a chemoattractant and an adhesion molecule on endothelial cells activated by proinflammatory cytokines. In this study, we investigated the effects of genistein (5-25 muM) on fractalkine expression in human umbilical vein endothelial cells (HUVECs) and on its receptor, CX3CR1, in THP-1 cells in response to treatment with tumor necrosis factor (TNF)- alpha. TNF-alpha significantly induced fractalkine expression in endothelial cells. Genistein decreased TNF-alpha-induced fractalkine expression through suppression of Akt and p38 phosphorylation and NF-kappaB activities. Genistein also strongly suppressed TNF-alpha-induced expression of CX3CR1 in monocytes. Genistein suppressed TNF-alpha-stimulated adhesion of monocytes to HUVECs. Immunohistochemical analysis revealed that genistein suppressed the in vivo lipopolysaccharide (LPS)-induced arterial endothelial fractalkine expression in the heart, kidney, and small intestine. These results suggest that genistein may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury under vascular inflammatory conditions.

Numerous studies have shown that the levels of matrix metalloproteinase (MMP)-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. This study investigated the effects of caffeic acid phenethyl ester (CAPE), a chemopreventive phytochemical derived from honeybee propolis, on the invasive phenotype of SK-Hep1 human hepatocellular carcinoma cells (SK-Hep1 cells). CAPE effectively suppressed SK-Hep1 cell invasion in a dose-dependent manner. The constitutive expression of MMP-2 and MMP-9 in SK-Hep1 cells was almost completely abolished by treatment with 12.5 muM CAPE. CAPE also significantly inhibited nuclear factor kappa B (NF-kappaB) DNA-binding activity in SK-Hep1 cells. These results taken together suggest that CAPE exerts antimetastatic potential through inhibition of MMP-2 and MMP-9 expression, possibly by targeting NF-kappaB in hepatocellular carcinoma.

Abnormal upregulation of cyclooxygenase-2 (COX-2) has been frequently observed in various types of transformed and cancerous cells. Numerous anti-inflammatory agents have been shown to exert chemopreventive effects by targeting COX-2, a rate-limiting enzyme involved in the inflammatory process. Anthocyanins are naturally occurring polyphenolic compounds that endow various fruits, vegetables, and plants with intense colors. Peonidin is another representative anthocyanidin, but its chemopreventive potential has not been fully described. This article investigated the effect of peonidin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression and transformation in JB6 P(+) mouse epidermal cells (JB6 P(+) cells). Treatment of JB6 P(+) cells with peonidin inhibited TPA-induced COX-2 expression, and also decreased TPA-induced neoplastic transformation and blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs) in the cells. The inhibition of the signaling mechanism regulating the activation of ERKs strongly suggests that peonidin exhibits chemopreventive as well as anti-inflammatory activities.

cope Natural compounds that regulate peroxisome proliferator-activated receptor alpha (PPARα) have been reported to have beneficial effects in obesity-mediated metabolic disorders. In this study, we demonstrated that biochanin A (BA), an agonist of PPAR-α, improved hepatic steatosis and insulin resistance by regulating hepatic lipid and glucose metabolism. Methods and results C57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), and an HFD supplemented with 0.05% BA for 12 weeks. Histological and biochemical examinations indicated that BA prevented obesity-induced hepatic steatosis and insulin resistance in HFD-fed mice. BA stimulated the transcriptional activation of PPAR-α in vitro and increased the expression of PPAR-α and its regulatory proteins in the liver. CE-TOF/MS analyses indicated that BA administration promoted the recovery of metabolites involved in phosphatidylcholine synthesis, lipogenesis, and beta-oxidation in the livers of obese mice. BA also suppressed the levels of gluconeogenesis-related metabolites and the expression of the associated enzymes, glucose 6-phosphatase and pyruvate kinase. Conclusion Taken together, these results showed that BA ameliorated metabolic disorders such as hepatic steatosis and insulin resistance by modulating lipid and glucose metabolism in diet-induced obesity. Thus, BA may be a potential therapeutic agent for the prevention of obesity-mediated hepatic steatosis and insulin resistance.

The purpose of this study is to investigate the effects of euphorbiasteroid, a component of Euphorbia lathyris L., on adipogenesis of 3T3-L1 pre-adipocytes and its underlying mechanisms. Euphorbiasteroid decreased differentiation of 3T3-L1 cells via reduction of intracellular triglyceride (TG) accumulation at concentrations of 25 and 50 μM. In addition, euphorbiasteroid altered the key regulator proteins of adipogenesis in the early stage of adipocyte differentiation by increasing the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, levels of adipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α, were decreased by euphorbiasteroid treatment at the late stage of adipocyte differentiation. The anti-adipogenic effect of euphorbiasteroid may be derived from inhibition of early stage of adipocyte differentiation. Taken together, euphorbiasteroid inhibits adipogenesis of 3T3-L1 cells through activation of the AMPK pathway. Therefore, euphorbiasteroid and its source plant, E. lathyris L., could possibly be one of the fascinating anti-obesity agent.

The antidiabetic effect of the Citrus junos Tanaka (also known as yuja or yuzu) was examined. Ethanol extract of yuja peel (YPEE) significantly stimulated 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) uptake in C2C12 myotubes. However, ethanol extract of yuja pulp (YpEE) and water extract of yuja peel (YPWE) or pulp (YpWE) did not stimulate glucose uptake. In addition, peroxisome proliferator-activated receptor gamma (PPAR-γ) and AMP-activated protein kinase (AMPK) activities were increased by YPEE in a dose-dependent manner. Pretreatment of AMPK inhibitor decreased the glucose uptake stimulated by YPEE in C2C12 myotubes. We confirmed the anti-diabetic effect of YPEE in mice fed a high fat-diet (HFD). Compared with control mice on a normal diet (ND), these mice showed increased body weight, liver fat, insulin resistance, triacylglycerol (TG), and total cholesterol content. Addition of 5% YPEE significantly reduced the weight gain and rise in liver fat content, serum triacylglycerol (TG), total cholesterol, and insulin resistance found in mice fed a high-fat diet (HFD). Moreover, YPEE reduced the secretion of HFD-induced adipocytokines such as leptin and resistin. YPEE also resulted in increased phosphorylation of AMPK in muscle tissues. These results suggest that ethanol extract of yuja peel exerts anti-diabetic effects via AMPK and PPAR-γ in both cell culture and mouse models.

The present study investigated immunopotentiating activities of lactic acid bacteria isolated from kimchi (KLAB) in vitro. A RAW264.7 macrophage cell line was stimulated with four strains of KLAB and two strains of bifidobacteria, and then the production of nitric oxide (NO) and cytokines--tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)--was determined. Lactobacillus plantarum, a lactic acid bacteria involved in the latent fermentation of kimchi, was the most effective for the generation of NO, TNF-alpha, and IL-6 in macrophage. All strains generated NO, while for the TNF-alpha and IL-6, only L. plantarum had significant activity. Our results indicate that L. plantarum plays an important role in the immunopotentiating activity of kimchi.

We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine- and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH). C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight·daily (MCD+D200), and MCD diet supplemented with EDL at 500 mg/kg body weight·daily (MCD+D500). Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-α and IL-6; and levels of caspase-3 and pJNK/JNK protein. Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH. Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-α, and IL-6; on the contrary, the levels of reduced GSH increased. At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK. These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities.

The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease.

This study was designed to evaluate the effects and mechanism of Platycodi radix, having white balloon flower (Platycodon grandiflorum for. albiflorum (Honda) H. Hara) on obesity and insulin resistance. The extracts of Platycodi radix with white balloon flower were tested in cultured cells and administered into mice on a high-fat diet. The Platycodi radix activated the AMPK/ACC phosphorylation in C2C12 myotubes and also suppressed adipocyte differentiation in 3T3-L1 cells. In experimental animal, it suppressed the weight gain of obese mice and ameliorated obesity-induced insulin resistance. It also reduced the elevated circulating mediators, including triglyceride (TG), T-CHO, leptin, resistin, and monocyte chemotactic protein (MCP)-1 in obesity. As shown in C2C12 myotubes, the administration of Platycodi radix extracts also recovered the AMPK/ACC phosphorylation in the muscle of obese mice. These results suggest that Platycodi radix with white balloon flower ameliorates obesity and insulin resistance in obese mice via the activation of AMPK/ACC pathways and reductions of adipocyte differentiation.

As angiogenesis plays important roles in tumor growth and metastasis, searching for antiangiogenic compounds is a promising tactic for treating cancers. Cafestol, a diterpene found mainly in unfiltered coffee, provides benefit through varied biological activity, including antitumorigenic, antioxidative, and anti-inflammatory effects. This study aimed to investigate the effects of cafestol on angiogenesis and to uncover the associated mechanism. We show that cafestol inhibits angiogenesis of human umbilical vascular endothelial cells. This inhibition affects the following specific steps of the angiogenic process: proliferation, migration, and tube formation. The inhibitory effects of cafestol are accompanied by decreasing phosphorylation of FAK and Akt and by a decrease in nitric oxide production. Overall, cafestol inhibits angiogenesis by affecting the angiogenic signaling pathway.

We used UPLC-Q-TOF MS to analyze hepatic metabolites of rats aged 6, 12, 18, and 24 months; the MS data were processed by partial least-squares discriminant analysis (PLS-DA) to investigate the discrimination among sample groups. Rats were significantly separated with increasing age, except those aged between 6 and 12 months. We identified only 25 of 120 metabolites contributing to the separation: lipid metabolites (glycerol-3-phosphate, linolenic acid, lysophosphatidylcholines [lysoPCs]), energy metabolism intermediates (betaine, carnitine, acylcarnitines, creatine, pantothenic acid), nucleic acid metabolites (inosine, xanthosine, uracil, hypoxanthine, xanthine), and tyrosine. Aging accumulated energy metabolism intermediates, hypoxanthine, xanthine, and 2 major lysoPCs (C18:0 and C22:6). The NAD level and NAD/NADH ratio decreased with age. It was indicated that aging might decrease energy production through β-oxidation because of a decrease in NAD despite the accumulation of lipid energy metabolism intermediates. In addition to energy dysregulation, hypoxanthine and xanthine, which are elevated with age, might accumulate reactive oxygen species in the liver. These results strongly support two aging theories: those of energy dysregulation and free radicals. Additionally, we propose a metabolic pathway related to aging based on these hepatic metabolites. These metabolites and the proposed aging pathway could be used to understand aging and related diseases better, and increase the predictability of aging risk.

Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known to possess beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. Treatment with 100 μM tangeretin significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin-stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA transfection prevented the glucose uptake stimulated by tangeretin. We also examined the anti-diabetic properties of tangeretin in mice on HFD. Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight gain, glucose tolerance, total cholesterol levels, and the secretion of adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover, AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected from the cell system. These results suggest that tangeretin exerts anti-diabetic effects in both cell culture and mouse models, and these effects are necessary for activating AMPK.