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This study was performed to investigate the effects of ethanolic extract of Ulmus davidiana root (UE) on lipid metabolism in mice fed a high-fat diet (HF) for 7 weeks. Forty male ICR mice were randomly divided into four groups; normal diet group (N), high-fat diet group (HF), HF with 0.5% UE (HF-L) and 1% UE (HF-H) group. Body weight, body weight gain, and liver weight in the HF group was significantly higher than in the N group, while those of the HF-L and HF-H group were unchanged. UE improved HF-induced dyslipidemia by reducing serum triglyceride, total cholesterol, and the atherogenic index. There was no difference in serum HDL-cholesterol among experimental groups. However, the HDL-cholesterol/total cholesterol ratio was significantly increased in the HF-L and HF-H group. Histological analysis showed that HF-fed mice developed hepatocellular microvesicular vacuolation as a result of fat accumulation. These changes were attenuated by 1% UE supplementation. In addition, hepatic triglyceride and cholesterol levels in the HF-H group significantly reduced. Taken together, these results demonstrated that lipid levels in the blood and liver were reduced by UE, suggesting that it might be beneficial for the prevention and treatment of hyperlipidemia and fatty liver.Key words: Ulmus davidiana root extract, high-fat diet, lipid metabolism, serum lipids, hepatic fat accumulation

Licorice (Glycyrrhiza glabra Linne) is a well-known medicinal plant and glabridin is an isoflavan isolated from licorice. In this study, we investigated the anti-obesity effect of glabridin and glabridin-rich supercritical fluid extract of licorice (LSC). Glabridin effectively inhibited adipogenesis in 3T3-L1 cells. Moreover, LSC showed inhibitory effect on adipogenesis in a dose-dependent manner. The inhibitory effect of LSC resulted from inhibiting the induction of the transcriptional factors CCAAT enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma. Then we fed mice with high-fat diet containing none, 0.1% and 0.25% LSC for 8weeks to explore the anti-obesity effect of LSC in vivo. LSC significantly reduced weight gain by high-fat diet in a dose-dependent manner. The reductions of the hypertrophy of white adipose tissue and of fat cell size were also observed. In the liver, LSC supplementation effectively inhibited high-fat diet-induced hepatic steatosis through downregulation of gluconeogenesis related phosphoenolpyruvate carboxykinase and glucose 6-phosphatase and upregulation of the β-oxidation related carnitine palmitoyltransferase 1. Taken together, our results suggest that glabridin and glabridin-rich licorice extract would be effective anti-obesity agents.

Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S) with an [M - H](-) ion at m/z 217. While M2 showed an [M - H](-) ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine.

This study was conducted to investigate the physicochemical properties of the ethanol extracts and soluble dietary fiber from Cassia tora L. seed. The proximate composition of Cassia tora, soluble solid contents, color intensity and contents of emodin and rhein of Cassia tora extract, molecular mass distribution, sugar contents and viscosity of soluble fiber from Cassia tora were analyzed. Cassia tora contains 12.6% of moisture, 5.2% of ash, 13.4% of crude protein, 7.2% of crude fat, 8.8% of insoluble fiber and 48.3% of soluble fiber. The effects of extract condition on soluble solid contents, color intensity and contents of emodin and rhein of Cassia tora extract were investigated. The soluble solid contents were higher in 70% or 50% ethanol extracts than those in 100% ethanol extracts and showed highest value in grind sample extracts. In Hunter's color value, 100% ethanol extracts and whole Cassia tora sample extracts were higher in L and b value, but on the contrary, were lower in a value, than those of the other. The highest emodin and rhein contents were observed in 70% and 50% ethanol extracts, respectively, and showed higher value in room temperature extracts than in heating extracts. The molecular mass of soluble fiber from Cassia tora seed was estimated by gel filtration chromatography. Most soluble fiber(80%) exhibited a molecular mass range of between 50~2000 kDa. The major sugars of soluble fiber from Cassia tora seed were identified as xylose, mannose and galactose. The apparent viscosity of 0.5% soluble fiber from Cassia tora seed was 33 mPas showing a higher value than pectin or xanthan gum.

cope Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Here, we investigated the protective effect of lycopene on high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation by miRNA regulation. Methods and results C57BL/6J mice were fed high-fat diet with or without 0.05% lycopene for 8 weeks. Hepa 1–6 cells were treated with stearic acid (SA) after 24 h pretreatment with lycopene. Treatment of lycopene improved hepatic steatosis in high-fat-fed mice and reduced intracellular lipid accumulation induced by SA in Hepa 1–6 cells. We demonstrated that miR-21 expression was decreased in livers from high-fat diet-fed mice and Hepa 1–6 cells treated with SA. Lycopene normalized the downregulation of miR-21, which led to the downregulation of fatty acid-binding protein 7 (FABP7), a direct target of miR-21, at both the transcriptional and translational levels. This specific negative regulation of miR-21 was achieved by targeting the FABP7 3′UTR. Upregulation of miR-21 markedly blocked SA-induced intracellular lipid accumulation by blocking FABP7 expression. Moreover, silencing of FABP7 reduced SA-evoked lipid accumulation in Hepa 1–6 cells. Conclusion The results suggest that lycopene may be a useful functional compound for treating NAFLD by regulating hepatic lipid metabolism.

Numerous medicinal plants and their derivatives have been reported to prevent obesity and related diseases. Although Syzygium aromaticum has traditionally been used as an anodyne, carminative and anthelmintic in Asian countries, its potential in the prevention and treatment of obesity has not yet been explored. Therefore, the present study investigated the anti-obesity effect of S. aromaticum ethanol extract (SAE) both in vitro and in vivo. To evaluate the anti-obesity potential of SAE in vitro, the effect of SAE treatment on adipocyte differentiation in 3T3-L1 cells was investigated. To evaluate its potential in vivo, mice were assigned to three groups: a group fed the American Institute of Nutrition AIN-76A diet (normal group), an experimental group fed a high-fat diet (HFD group) and an experimental group fed an HFD supplemented with 0.5% (w/w) SAE (HFD + SAE group). After 9 weeks of feeding, the body weight; white adipose tissue (WAT) mass; serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, glucose, insulin and leptin; hepatic lipid accumulation; and levels of lipid metabolism-related genes in the liver and WAT were measured. In vitro investigation of the effect of SAE treatment on 3T3-L1 cells revealed that it had efficiently inhibited the conversion of cells into adipocytes in a dose-dependent manner. In vivo investigation revealed that SAE supplementation had significantly decreased HFD-induced increases in the body weight, liver weight, WAT mass, and serum TG, TC, lipid, glucose, insulin and leptin levels. Consistent with its effects on liver weight and WAT mass, SAE supplementation was found to have suppressed the expression of lipid metabolism-related proteins, including SREBP-1, FAS, CD36 and PPARγ in the liver and WAT, in addition to downregulating mRNA levels of transcription factors including Srebp and Pparg. SAE inhibits fat accumulation in HFD-fed mice via the suppression of transcription factors integral to adipogenesis and lipogenesis, suggesting its potential in preventing obesity.

This study was aimed to clarify the effect of defatted chufa (Cyperus esculentus L., DC) on diet-induced obesity and lipid metabolism in mice. C57BL/6J mice were fed 1 of 4 experimental diets for 7 weeks: a normal diet (N), a high-fat diet (HF), a high-fat diet with 5% DC (LDC), and a high-fat diet with 10% DC (HDC). DC supplementation (10%) significantly reduced body weight gain, adipose tissue weight, and adipocyte size increased by high-fat diet although there was no significant difference between HF group and LDC group. Serum total cholesterol and triglyceride levels of the HDC group were significantly decreased compared to those of the HF group. The hepatic triglyceride levels also decreased significantly with 10% DC supplementation, but not changed with 5% DC supplementation. Serum insulin and leptin levels in the LDC and HDC groups were significantly decreased compared to those of the HF group. These results suggest that defatted chufa may be useful for the prevention of diet-induced obesity and hyperlipidemia.

To understand the molecular mechanisms underlying the influence of quercetin on the physiological effects of hyperlipidemia, we investigated its role in the prevention of high-fat diet (HFD)-induced obesity and found that it regulated hepatic gene expression related to lipid metabolism. Quercetin supplementation in mice significantly reduced the HFD-induced gains in body weight, liver weight, and white adipose tissue weight compared with the mice fed only with HFD. It also significantly reduced HFD-induced increases in serum lipids, including cholesterol, triglyceride, and thiobarbituric acid-reactive substance (TBARS). Consistent with the reduced liver weight and white adipose tissue weight, hepatic lipid accumulation and the size of lipid droplets in the epididymal fat pads were also reduced by quercetin supplementation. To further investigate how quercetin may reduce obesity, we analyzed lipid metabolism-related genes in the liver. Quercetin supplementation altered expression profiles of several lipid metabolism-related genes, including Fnta, Pon1, Pparg, Aldh1b1, Apoa4, Abcg5, Gpam, Acaca, Cd36, Fdft1, and Fasn, relative to those in HFD control mice. The expression patterns of these genes observed by quantitative reverse transcriptase-polymerase chain reaction were confirmed by immunoblot assays. Collectively, our results indicate that quercetin prevents HFD-induced obesity in C57B1/6 mice, and its anti-obesity effects may be related to the regulation of lipogenesis at the level of transcription. Copyright © 2012 John Wiley & Sons, Ltd.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and is presently the most common chronic liver disease. However, the mechanisms underlying the development of steatosis remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that modulate a variety of biological functions. We have investigated the role of miRNA in the development of steatosis. We found that miR-467b expression is significantly downregulated in liver tissues of high-fat diet fed mice and in steatosis-induced hepatocytes. The downregulation of miR-467b resulted in the upregulation of hepatic lipoprotein lipase (LPL), the direct target of miR-467b. Moreover, the interaction between miR-467b and LPL was associated with insulin resistance, a major cause of NAFLD. These results suggest that downregulation of miR-467b is involved in the development of hepatic steatosis by modulating the expression of its target, LPL.

This study qualitatively and quantitatively analyzed various carotenoids, L-ascorbic acid, and tocopherol and their anti-oxidant properties from four varieties (Special, Chelsea, Cupra, and Fiesta) and three different color stages (green (GP), yellow (YP) and red (RP)) of paprika harvested in Korea. Seven carotenoids were identified, mainly lutein in GP (Special: 4.65±0.84 mg/kg fresh weight (fw)) and YP (Fiesta: 5.19±0.05 mg/kg fw), and capsorubin (3.16±0.35 mg/kg fw) and capsanthin (53.70±6.23 mg/kg fw) in Special of RP. RP was the highest in total carotenoids, L-ascorbic acid, and α-tocopherol contents, while GP was the highest in γ-tocopherol content. RP showed the strongest antioxidant activity (IC 50 =62.40±0.03 µg/mL in an ABTS assay and 182.77±31.74 µg/mL in a DPPH assay). Paprika in different color stages has many phytochemicals even though they have different kinds of carotenoids. Therefore, dietary intake of paprika may be helpful for improving human health.

Scope: Natural dietary anti-obesogenic phytochemicals may help combat the rising global incidence of obesity. We aimed to identify key hepatic pathways targeted by anti-obsogenic ginger phytochemicals fed to mice. Methods and results: Weaning mice were fed a high-fat diet containing 6-gingerol (HFG), zerumbone (HFZ), a characterized rhizome extract of the ginger-related plant Alpinia officinarum Hance (high fat goryankang, HFGK) or no phytochemicals (high-fat control, HFC) for 6 wks and were compared with mice on a low-fat control diet (LFC). Increased adiposity in the HFC group, compared with the LFC group, was significantly (p

Estrogenic activities of ethanol extract and its active components from Psoralea corylifolia L. were studied using various in vitro assays. The main components from ethanol extract were analyzed to be bakuchiol, psoralen, isobavachalcone, isobavachromene, and bavachinin. In a fractionation procedure, hexane and chloroform fractions showed estrogenic activity in yeast transactivation assay and E-screen assay. In yeast transactivation assay, ethanol extract, hexane, and chloroform fractions showed significantly higher activities at a concentration of 1.0 ng/ml, and bakuchiol at the concentration of 10(-6) M was showed the highest activity, especially, which was higher than genistein at the same concentration. In E-screen assay, cell proliferation of bakuchiol (10(-6) M) showed similar estrogenic activity with genistein (10(-6) M). In ER binding assay, bakuchiol displayed the strongest ER-binding affinity (IC(50) for ERα=1.01×10(-6) M, IC(50) for ERβ=1.20×10(-6) M) and bakuchiol showed five times higher affinity for ERα than for ERβ.

The anti-diabetic potential of watermelon (Citrullus vulgaris Schrad) was evaluated in vivo. ICR mice were fed experimental diet containing none, 10% watermelon flesh powder (WM-P) or 1% watermelon rind ethanol extract (WM-E). At the end of 4 weeks, mice were administrated with streptozotocin (40 mg/kg, i.p.) for 5 consecutive days to induce diabetes. Supplementation with WM-E significantly decreased blood glucose level and increased serum insulin levels. Feeding of WM-P also induced moderate changes but those were not statistically significant. Immunohistochemical analysis showed watermelon effectively protected pancreatic cells death. These results suggest that watermelon has a beneficial effect on diabetes.

This study was performed to investigate the anti-obesity effect of Eisenia bicyclis in mice fed a high-fat diet (HFD). Male C57BL/6J mice were divided into three groups that were fed a normal diet, an HFD, or an HFD supplemented with a 5% powder of Eisenia bicyclis (PEB) for 8 weeks. The PEB group showed lower body weight gains than the HFD group. The PEB group also exhibited reduced body fat mass and adipose cell size in epididymal adipose tissue. The concentrations of serum cholesterol, leptin, and insulin in the PEB group were significantly lower than those in the HFD group. Liver triglyceride content was significantly decreased by PEB supplementation. Furthermore, hematoxylin and eosin staining revealed that PEB supplementation reduced lipid droplet formation in the liver induced by HFD. These results suggest that PEB supplementation reduces body weight gain and fat accumulation in HFD-induced obese mice.

This study was carried out to examine the effects of ethanol extract (EXPG) and saponin (SAP) from Platycodon grandiflorum on scopolamine-induced amnesia in mice. Fifty male ICR mice were assigned to five groups--normal (normal diet + saline), control (normal diet + scopolamine), EXPG 0.2% (normal diet + 0.2% EXPG + scopolamine), EXPG 0.5% (normal diet + 0.5% EXPG + scopolamine), and SAP 0.02% (normal diet + 0.02% SAP + scopolamine)--and fed each diet ad libitum. After 4 weeks of feeding the appropriate diet, scopolamine (1 mg/kg, i.p.) was given to mice 45 minutes before the passive avoidance and Morris water maze tasks. Both the EXPG groups and the SAP group exhibited significant amelioration of scopolamine-induced amnesia as measured in both the passive avoidance task and the Morris water maze task. Moreover, acetylcholinesterase (AChE) activity and the levels of thiobarbituric acid-reactive substance (TBARS) in the serum and brain of the EXPG groups were lower than those of the control group. These results suggest that EXPG may improve the cognitive deficit caused by scopolamine and that these effects might be due to EXPG mediated by inhibition of AChE activity and inhibition of TBARS.

We investigated the anti-obesity effect of berberine in mice fed a high fat diet and focused on the analysis of adipogenesis in epdidymal adipose tissue. Male C57BL/6J mice were divided into three groups, which were fed either a normal diet (Nor), a high fat diet (HFD), or a high fat diet plus orally administered berberine (0.2 g /㎏ body weight) (HFD+B) for 8 weeks. Relative to mice in the HFD group, mice in the HFD+B group showed significant reductions in weight gain and adipose tissue weight. Serum triglyceride levels in mice from the HFD+B group were significantly lower than those of the HFD mice, as were the levels of serum insulin and leptin. An effect of berberine to reduce epididymal adipose mass was revealed by H&E staining. Berberine inhibited the high fat diet-induced increase in levels of the proteins CD36 and CCAAT/enhancer-binding protein α (C/EBPα) observed in epididymal adipose tissues of mice from the HFD group. These results suggest that berberine has an anti-obesity effect in mice and that the effect is mediated by inhibition of adipogenesis.

Cherry tomatoes are rich in antioxidants, which may protect against neurodegeneration and consequent memory loss. This study was conducted to investigate the effect of cherry tomatoes on scopolamine-induced amnesia in mice. Male ICR mice (4 weeks old) were maintained for 4 weeks on a diet containing 10 or 20% tomato powder (TP), and then administered scopolamine (1 ㎎/㎏ body weight, i.p.) 45 min before memory testing. Passive avoidance and Morris water maze testing revealed that scopolamine-induced amnesia was significantly reduced in the TP groups compared to the non TP-received (control) group. Accordingly, acetylcholinesterase activities in the serum and brain of TP groups were lower than those in the control group. These findings suggest that cherry tomatoes may be useful for the prevention of neurodegenerative diseases such as amnesia and Alzheimer’s disease.

Agaricus bisporus, also known as white button mushroom, is one of the most popular mushrooms consumed in Korea. This mushroom contains high concentrations of flavanoids and exhibits antioxidant activity. In this study, we examined the effects of Agaricus bisporus ethanol extract (ABE) on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein levels were assessed in cells treated with 100 μM LPS in the presence or absence of ABE. 0.5 ㎎/mL of ABE suppressed NO production significantly. Moreover, ABE inhibited levels of iNOS protein. Taken together, these results suggest that ABE exerts anti-inflammatory activity in LPS-induced inflammation in RAW 264.7 cells.

The aim of the present study was to investigate whether ethanol extracts ofPsoralea corylifoliaL. (PCE) and its active component protect against bone loss in ovariectomised rats. We screened oestrogenic activities of the main extract fractions usingin vitroassays and identified bakuchiol as the most active oestrogenic component by HPLC and LC/MS, and then demonstrated that bakuchiol had strong binding affinity for oestrogen receptor (ER) α. Seventy female Sprague–Dawley rats were assigned to either a sham-operated group (n10) or an ovariectomised group (n60). The ovariectomised group was subdivided into six groups, each containing ten rats: vehicle group, two bakuchiol-treated groups (dose of 15 mg/kg per d or 30 mg/kg per d; ten rats for each group), two PCE-supplemented groups (0·25 % or 0·5 % extracts of diets; ten rats for each group) and a 17β-oestradiol (E2)-treated group (20 μg/kg per d). We recorded weight and feed intake every week, and killed all animals after 6 weeks. Blood was collected, and the uterus, kidneys and livers were removed. Bakuchiol has a three-fold higher binding affinity for ERα than for ERβ. Bakuchiol and PCE treatments had no uterotrophic activity even though they demonstrated oestrogenic activity in thein vitroassays. Bakuchiol and PCE treatments reduced postmenopausal bone loss by increasing alkaline phosphatase, Ca concentrations, serum E2 concentration and bone mineral density, and by decreasing the inorganic P level. The present study indicated that bakuchiol and PCE treatments could protect against bone loss.

This study was performed to examine the toxicity of Psoralea corylifolia L. by the single-dose oral toxicity tests in rat and bacterial reverse mutation assay. In single-dose oral toxicity tests, 5 mL ethanol extract of P. corylifolia L. were directly injected into 10 rats (5 males and 5 females) at a dosage of 2 g/kg. Death practice was not detected during breeding periods (14 days), and was calculated over 2 g/kg. No difference were observed with control group in the growth rate and histological observations. In bacterial reverse mutation assay, his(-) Salmonella Typhimurium TA98, TA100, TA1535, TA1537 and trp(-) Escherichia coli WP2uvrA (pKM101) were used for assessing the toxicity of ethanol extracts of P. corylifolia L.. No significant difference in formation of the colonies and no dose-dependent increase was observed regardless of the addition of S9 mix. The results showed that ethanol extracts of P. corylifolia L. did not have single-dose oral toxicity and mutagenic toxicity.

There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose tissue (WAT), increased the expression of brown adipocyte–specific genes (e.g., uncoupling protein 1 [UCP1]), decreased body weight gain, and ameliorated metabolic parameters in mice fed a high-fat diet. Consistently, BLC-treated mice showed significantly higher energy expenditure compared with control mice. In vitro, BLC increased the expression of brown adipocyte–specific genes in stromal vascular fraction-differentiated adipocytes. BLC also controlled the expression of miR-382, which led to the upregulation of its direct target, Dio2. Upregulation of miR-382 markedly inhibited the differentiation of adipocytes into beige adipocytes, whereas BLC recovered beige adipocyte differentiation and increased the expression of Dio2 and UCP1. Our findings suggest that the BLC-mediated increase in the browning of WAT and the thermogenic capacity of BAT significantly results in increases in energy expenditure. Browning of WAT by BLC was partially controlled via the regulation of miR-382 targeting Dio2 and may lead to the prevention of diet-induced obesity.

β-laphachone (BLC) is a naphthoquinonea, originally isolated from a Bignoniaceae tree Tabebuia avellanedae Lorentz ex Griseb and has been extensively studied because it possesses a wide range of bi...

SIRT1 plays a key role in regulating metabolism, and SIRT1 activation may be a promising strategy to treat metabolic syndrome. This study investigated whether zerumbone ameliorated diet-induced obe...

Shikonin is a naturally occurring naphthoquinone pigment and a major component of Lithospermum erythrorhizon. Our previous study showed that shikonin inhibited adipocyte differentiation in 3T3-L1 c...

BACKGROUND Black rice is rich in anthocyanins, especially cyanidin-3-glucoside (C3G). This study examined the effects of a C3G-rich extract from black rice on hyperlipidaemia induced by a high fat/cholesterol diet (HFCD) in rats. RESULTS Male Sprague–Dawley rats were fed either HFCD or HFCD containing 150 mg kg−1 body weight C3G (HFCD+C3G) for 4 weeks. We found that C3G significantly decreased serum levels of total cholesterol, free cholesterol, triglycerides, and free fatty acids in rats fed a HFCD. Similarly, hepatic cholesterol and triglyceride levels and the activities of hepatic lipogenic enzymes (malic enzyme and glucose-6-phosphate dehydrogenase) were significantly reduced by C3G supplementation. CONCLUSION These results suggest that C3G can ameliorate HFCD-induced hyperlipidaemia in part by modulating the activities of hepatic lipogenic enzymes. © 2013 Society of Chemical Industry

1 Phorbol ester decreases muscle tension in the rat myometrium, and the effect is more potent in latepregnant myometrium than in nonpregnant myometrium. In the present study, we have examined the contribution of protein kinase C (PKC) isoforms to the phorbol ester-induced inhibition of tension in rat uterine smooth muscle. 2 Thymeleatoxin (THX), a selective activator of conventional-type PKC (cPKC), and 12deoxyphorbol 13-isobutyrate (DPB), an activator of pan PKC, inhibited the tension induced by high K + , and inhibitions were significantly increased in pregnant myometrium compared to nonpregnant myometrium. The inhibition by DPB and THX of high K + -induced tension was significantly attenuated when PKC was downregulated by long-term pretreatment with THX and inhibited by Go6976, a cPKC inhibitor. 3 Of the cPKCs, PKCa is predominantly expressed in the rat myometrium, as detected by Western blot analysis. The expression of PKCa gradually increases from the beginning of gestation, reaching a maximum at day 21 of pregnancy. Treatment with DPB induced PKCa to translocate from the cytosol to the membrane in the pregnant myometrium. PKCe and PKCz, other dominant PKC isoforms in the rat myometrium, decrease during gestation, reaching a minimum in late pregnancy. 4 These results suggest that cPKC may be at least partly involved in the PKC-mediated inhibition of muscle tension in the rat myometrium. British Journal of Pharmacology (2003) 139, 408 – 414. doi:10.1038/sj.bjp.0705237

This study was designed to evaluate the effect of ovariectomy on nutrikinetics of genistein metabolites. To characterize the time-dependent changes in genistein metabolite concentrations, we identified 13 genistein metabolites using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The nutrikinetics of the individual metabolites at different time points were analyzed. Nutrikinetic analysis showed that genistein, genistein 4'-glucuronide, genistein 7-glucuronide, 3-hydroxygenistein, and hippuric acid showed relatively high bioavailability in the sham group compared to that in the ovariectomy group, suggesting that ovariectomy likely results in lower genistein bioavailability. These results may be related to alteration of gut microbiota by ovariectomy. The relative abundance of species of the Parabacteroides, Dorea, and Butyricimonas genera, and Desulfovibrionaceae_unclassified, Lachnospiraceae_unclassified, and Rikenellaceae_unclassified families increased in the ovariectomy group while the relative abundance of 523_7_unclassified and Y52_unclassified_unclassified increased in the sham group. These results suggest that gut microbiota alteration by ovariectomy may affect genistein bioavailability.

Agaricus bisporus (white button mushroom, WBM) is widely consumed in most countries and is reported to have anti-inflammatory and antioxidant activities. However, little is known regarding its effects in dextran sulfate sodium (DSS)-induced colitis, which are related to dysfunction of intestinal immunity. The aim of the present study was to investigate the effects of WBMs in an animal model of DSS-induced colitis. Male, 4-week-old ICR mice (n=10 per group) were fed a normal diet with or without 10% WBM for 4 weeks, and colitis was induced by 3% DSS in drinking water for 7 days. WBMs prevented DSS-induced shortening of colon length (P=.033) and diminished diarrhea (P=.049) and gross bleeding (P=.001), resulting in a decreased disease activity index. Results of histological analysis showed that WBMs suppressed mucosal damage. In addition, WBMs attenuated the DSS-induced increase in myeloperoxidase activity (P=.012) and upregulation of proinflammatory cytokine tumor necrosis factor-α (P=.020) in the colon segment. Taken together, these findings suggest a possible role for the WBM as an immunomodulator that can prevent and/or treat ulcerative colitis.

Mitochondrial dysfunction is associated with the pathophysiology of insulin resistance. Allylisothiocyanate (AITC) is found in many cruciferous vegetables and has been reported to possess anticancer activity. However, the effect of AITC on insulin resistance and mitochondrial function has not yet been investigated. Here, we show that AITC increased glucose uptake in insulin-resistant C2C12 myotubes and augmented glucose transporter 4 (GLUT4) translocation in L6-GLUT4myc cells. AITC recovered the impaired insulin signaling evoked by free fatty acid exposure and increased mitochondrial membrane potential and mitochondrial DNA content. AITC also elevated the rate of oxygen consumption in C2C12 cells. Furthermore, mice that were fed a high-fat diet with AITC for 10 weeks had reduced diet-induced obesity and hepatic steatosis. AITC also inhibited the hyperglycemia and hyperinsulinemia induced by the consumption of a high-fat diet. Glucose and insulin tolerance tests indicated that AITC improved both glucose tolerance and insulin sensitivity. In addition, AITC inhibited hepatic gluconeogenesis and ameliorated high fat diet-induced mitochondrial dysfunction. Collectively, these data suggest that the protective effect of AITC on insulin resistance is partly mediated through the modulation of mitochondrial dysfunction.

Although rice has been shown to have beneficial health effects, little is known about the effect of rice on hepatic lipid accumulation as a carbohydrate source. This study investigated the effects and mechanism of action of cooked rice on high-fat diet (HF)-induced fat accumulation. The C57BL/6 mice were divided into three groups and fed a normal diet (NOR), HF, or HF with cooked rice (HF-CR) for 12 weeks. The HF-CR-fed mice had significantly lower body weight gains and abdominal fat mass compared with the HF-fed mice. Consuming cooked rice resulted in significantly lower serum total cholesterol, low-density lipoprotein cholesterol, hepatic lipid content, and lipid droplet number and size. Cooked rice consumption also suppressed the HF-induced increase in expression of lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl CoA desaturase 1 (SCD-1), peroxisome proliferator-activated receptor gamma (PPARγ), and CD36. The expression of cholesterol metabolism-related genes, such as acyl-CoA:cholesterol acyltransferase 1 (ACAT1), were also downregulated in the HF-CR-fed mice. Cooked rice may prevent HF-induced fat accumulation by regulating lipid metabolism-related gene expression, and it may be a useful carbohydrate source for preventing nonalcoholic fatty liver disease.

Objective The aim of this study was to evaluate the effects of rice as a carbohydrate source and its molecular mechanisms on insulin resistance induced by a high-fat diet (HFD). Methods C57 BL/6 J mice were divided into three groups and were fed a low-fat diet (LFD); a HFD (with 18% fat, 0.5% cholesterol, 51.5% w/w cornstarch and sucrose); or a HFD with rice (HFD-CR, with 18% fat, 0.5% cholesterol and 51.5% w/w rice powder) for 12 wk. In the HFD-CR diet, cooked rice powder was substituted for cornstarch and sucrose in the HFD as a carbohydrate source. Results HFD-CR–fed mice had significantly lower body weight, blood glucose, insulin and leptin levels and ameliorated glucose responses with decreased homeostasis model assessment-insulin resistance compared with HFD-fed mice. Hepatic mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were down-regulated in the HFD-CR group. The hypertrophied islet size and the decreased pancreatic mRNA expression of glucose transporter 2 in the HFD group were normalized with cooked rice consumption. Rice promoted glucose uptake by activating AMP-activated protein kinase and downstream glucose transporter 4 in the skeletal muscle. Conclusion Rice consumption as a carbohydrate source might potentiate improvements in glucose uptake via AMP-activated protein kinase activation and glucose transporter 4 expression in the skeletal muscles, thereby improving insulin sensitivity.

The aim of this study was to investigate the effects of isolated protein from white rice on lipid metabolism in a hypercholesterolemic animal model. Male Sprague-Dawley rats were divided into three groups and fed either a normal diet or a high-cholesterol diet (HCD) containing either casein or isolated rice protein for 4 weeks. Compared with rats fed a HCD with casein, the total cholesterol (TC) level in the plasma was significantly reduced in the rats fed rice protein. However, no significant differences were observed in the triglycerides, high-density lipoprotein (HDL), and glucose levels among the experimental groups. Hepatic total lipids and TC levels were significantly decreased by supplementation with rice protein. In addition, rice protein significantly increased the levels of TC and bile acids in the feces. These results suggest that rice protein may improve HCD-induced hypercholesterolemia by enhancing fecal excretion of cholesterol.

Eleutheroside E (EE), a principal component ofEleutherococcus senticosus(ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF-α-induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.

Anthricin (deoxypodophyllotoxin) is a natural product isolated fromAnthriscus sylvestris(L.) Hoffm. (Apiaceae). Here, we investigated the effect of anthricin on autophagy and mammalian target of rapamycin (mTOR) signaling as anticancer actions in breast cancer cells. Many studies have supported the contention that the phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 pathway is considerably deregulated in breast cancer and that autophagy plays important roles in the development of this type of cancer, although the exact underlying mechanisms remain unknown. Our data confirmed that anthricin markedly induced apoptosis in 2 breast cancer cell lines, MCF7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor, progesterone receptor, and Her2/Neu receptor negative). Anthricin treatment decreased the levels of phosphorylated Akt and mTORC1, followed by inhibition of cell growth. Interestingly, blockage of autophagy by a pharmacological inhibitor or genetic deletion of ULK1 and Atg13 accelerated anthricin-induced apoptosis, suggesting that autophagy has cytoprotective effects. Taken together, our results indicate that anthricin is an inhibitor of mTOR and that a combination of an autophagy inhibitor and anthricin may serve as a new promising strategy for the treatment of breast cancer cells.

Transplantation of spermatogonial stem cells (SSCs) in experimental animal models has been used to study germ line stem cell biology and to produce transgenic animals. The species-specific recipient model preparation is important for the characterization of SSCs and the production of offspring. Here, we investigated the effects of surgically induced cryptorchidism in dog as a new recipient model for spermatogonial stem cell transplantation. Artificially unilateral or bilateral cryptorchidism was induced in ten mature male dogs by surgically returning the testis and epididymis to the abdominal cavity. The testes and epididymides were collected every week after the induction of artificial cryptorchidism (surgery) for one month. To determine the effect of surgical cryptorchidism, the seminiferous tubule diameter was measured and immunohistochemistry using PGP9.5 and GATA4 antibodies was analyzed. The diameters of the seminiferous tubules of abdominal testes were significantly reduced compared to those of the scrotal testes. Immunohistochemistry results showed that PGP9.5 positive undifferentiated spermatogonia were significantly reduced after surgical cryptorchidism induction, but there were no significant changes in GATA-4 positive sertoli cells. To evaluate the testis function recovery rate, orchiopexy was performed on two dogs after 30 days of bilateral cryptorchidism. In the orchiopexy group, SCP3 positive spermatocytes were detected, and spermatogenesis was recovered 8 weeks after orchiopexy. In this study, we provided optimum experimental conditions and time for surgical preparation of a recipient canine model for SSC transplantation. Additionally, our data will contribute to recipient preparation by using surgically induced cryptorchidism in non-rodent species.

Curcumin is a well-known component of traditional turmeric (Curcuma longa), which has been reported to prevent obesity and diabetes. However, the effect of curcumin on hepatic lipid metabolism remains unclear. The aim of this study was to examine the effects of curcumin on hepatic steatosis in high-fat/cholesterol diet (HFD)-induced obese mice. Male C57BL/6J mice were fed a normal diet (ND), HFD or HFD with 0.15% curcumin (HFD+C) for 11 weeks. We found that curcumin significantly lowered the body-weight and adipose tissue weight of mice in the HFD+C group compared with the findings for the HFD group (p < 0.05). The levels of total cholesterol, fasting glucose and insulin in serum were decreased, and HFD-induced impairment of insulin sensitivity was improved by curcumin supplementation (p < 0.05). Curcumin protected against the development of hepatic steatosis by reducing hepatic fat accumulation. Moreover, curcumin activated AMP-activated protein kinase (AMPK) and elevated the gene expression of peroxisome proliferator-activated receptor alpha. By contrast, curcumin suppressed the HFD-mediated increases in sterol regulatory element-binding protein-1, acetyl-CoA carboxylase 1, fatty acid synthase and cluster of differentiation 36 expression. Taken together, these findings indicate that curcumin attenuates HFD-induced hepatic steatosis by regulating hepatic lipid metabolism via AMPK activation, suggesting its use as a therapeutic for hepatic steatosis.

Although Alpinia officinarum has been used in traditional medicine for the treatment of several conditions, such as abdominal pain, emesis, diarrhea, impaired renal function, and dysentery, little is known about its function in obesity. In this study, we investigated the antiobesity effect of A. officinarum ethanol extract (AOE) on lipid accumulation in 3T3-L1 cells and obesity in mice fed a high-fat diet (HFD). AOE dose-dependently suppressed lipid accumulation during differentiation of 3T3-L1 preadipocytes by downregulating CCAAT enhancer binding protein α (C/EBPα), sterol regulatory element binding protein-1 (SREBP-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) genes. Galangin, a major component of A. officinarum, had antiadipogenic effects in 3T3-L1 cells. AOE supplementation in mice fed a HFD revealed that AOE significantly decreased HFD-induced increases in body, liver, and white adipose tissue weights and decreased serum insulin and leptin levels. To elucidate the inhibitory mechanism of AOE in obesity, lipid metabolism-related genes were identified. AOE efficiently suppressed protein expressions of C/EBPα, fatty acid synthase, SREBP-1, and PPAR-γ in the liver and adipose tissue. The protein expression patterns, observed by immunoblot, were confirmed by quantitative real-time polymerase chain reaction. Collectively, these results suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes. AOE has potential for use as an antiobesity therapeutic agent that can function by regulating lipid metabolism.

Rice has many health-beneficial components for ameliorating obesity, diabetes, and dyslipidemia. However, the effect of cooked rice as a useful carbohydrate source has not been investigated yet; so we hypothesized that cooked rice may have hypolipidemic effects. In the present study, we investigated the effect of cooked rice on hyperlipidemia and on the expression of hepatic genes involved in lipid metabolism. Golden Syrian hamsters were divided into 2 groups and fed a high-fat (15%, wt/wt)/cholesterol (0.5%, wt/wt) diet supplemented with either corn starch (HFD, 54.5% wt/wt) or cooked rice (HFD-CR, 54.5% wt/wt) as the main carbohydrate source for 8 weeks. In the HFD-CR group, the triglyceride and total cholesterol levels in the serum and liver were decreased, and the total lipid, total cholesterol, and bile acid levels in the feces were increased, compared with the HFD group. In the cooked-rice group, the messenger RNA and protein levels of 3-hydroxy-3-methylglutaryl CoA reductase were significantly downregulated; and the messenger RNA and protein levels of the low-density lipoprotein receptor and cholesterol-7α-hydroxylase were upregulated. Furthermore, the expressions of lipogenic genes such as sterol response element binding protein-1, fatty acid synthase, acetyl CoA carboxylase, and stearoyl CoA desaturase-1 were downregulated, whereas the β-oxidation related genes (carnitine palmitoyl transferase-1, acyl CoA oxidase, and peroxisome proliferator-activated receptor α) were upregulated, in the cooked-rice group. Our results suggest that the hypolipidemic effect of cooked rice is partially mediated by the regulation of hepatic genes involved in lipid metabolism, which results in the suppression of cholesterol and fatty acid synthesis and the enhancement of cholesterol excretion and fatty acid β-oxidation.

Fisetin, a flavonol present in vegetables and fruits, possesses antioxidative and anti-inflammatory properties. In this study, we have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis. To evaluate whether fisetin regulates mTORC1 signaling, we investigated the phosphorylation and kinase activity of the 70-kDa ribosomal protein S6 kinase 1 (S6K1) and mTORC1 in 3T3-L1 preadipocytes. Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time- and concentration-dependent manner. To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells. The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt-dependent manner. Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity. Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of fisetin on mTOR. The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity, suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling. Fisetin supplementation in mice fed a high-fat diet (HFD) significantly attenuated HFD-induced increases in body weight and white adipose tissue. We also observed that fisetin efficiently suppressed the phosphorylation of Akt, S6K1 and mTORC1 in adipose tissue. Collectively, these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice. Therefore, fisetin may be a useful phytochemical agent for attenuating diet-induced obesity.

Black rice is rich in anthocyanins, especially cyanidin-3-glucoside (C3G). This study examined the effects of a C3G-rich extract from black rice on hyperlipidaemia induced by a high fat/cholesterol diet (HFCD) in rats.Male Sprague-Dawley rats were fed either HFCD or HFCD containing 150 mg kg⁻¹ body weight C3G (HFCD+C3G) for 4 weeks. We found that C3G significantly decreased serum levels of total cholesterol, free cholesterol, triglycerides, and free fatty acids in rats fed a HFCD. Similarly, hepatic cholesterol and triglyceride levels and the activities of hepatic lipogenic enzymes (malic enzyme and glucose-6-phosphate dehydrogenase) were significantly reduced by C3G supplementation.These results suggest that C3G can ameliorate HFCD-induced hyperlipidaemia in part by modulating the activities of hepatic lipogenic enzymes.

We investigated the anti-obesity effect of abietic acid in mice fed a high-fat diet with emphasis on changes in adipogenesis in epididymal adipose tissues. Male C57BL/6J mice were divided into four groups and fed a normal diet, a high-fat diet (HFD), or HFD plus oral administration of abietic acid (20 mg/kg of body weight/day [LA] or 40 mg/kg of body weight/day [HA]) for 8 weeks. Compared with the HFD group, mice orally administered 40 mg of abietic acid/kg of body weight/day exhibited significantly decreased body weight and adipose tissue weights. Serum triglyceride concentrations in the HA group were significantly lower than those in the HFD group, as were the levels of serum insulin and leptin. Hematoxylin and eosin staining revealed that epididymal adipose tissue mass was decreased by abietic acid administration. Abietic acid also inhibited the protein expression of sterol regulatory element-binding protein-1c, CCAAT/enhancer-binding protein α, and CD36 in epididymal adipose tissues, which are up-regulated by HFDs. These data demonstrate that abietic acid has an anti-obesity effect in mice mediated by the regulation of adipogenesis.

To understand the molecular mechanisms underlying the influence of quercetin on the physiological effects of hyperlipidemia, we investigated its role in the prevention of high-fat diet (HFD)-induced obesity and found that it regulated hepatic gene expression related to lipid metabolism. Quercetin supplementation in mice significantly reduced the HFD-induced gains in body weight, liver weight, and white adipose tissue weight compared with the mice fed only with HFD. It also significantly reduced HFD-induced increases in serum lipids, including cholesterol, triglyceride, and thiobarbituric acid-reactive substance (TBARS). Consistent with the reduced liver weight and white adipose tissue weight, hepatic lipid accumulation and the size of lipid droplets in the epididymal fat pads were also reduced by quercetin supplementation. To further investigate how quercetin may reduce obesity, we analyzed lipid metabolism-related genes in the liver. Quercetin supplementation altered expression profiles of several lipid metabolism-related genes, including Fnta, Pon1, Pparg, Aldh1b1, Apoa4, Abcg5, Gpam, Acaca, Cd36, Fdft1, and Fasn, relative to those in HFD control mice. The expression patterns of these genes observed by quantitative reverse transcriptase-polymerase chain reaction were confirmed by immunoblot assays. Collectively, our results indicate that quercetin prevents HFD-induced obesity in C57B1/6 mice, and its anti-obesity effects may be related to the regulation of lipogenesis at the level of transcription.

In the previous report, we have demonstrated that ginsenoside Rc, one of major ginsenosides, is a major component for the restoration for normal growth of worms in cholesterol-deprived medium. In the present study, we further investigated the roles of minor ginsenosides, such as ginsenoside Rh1 and Rh2, ginsenoside metabolites such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) and ginsenoside epimers such as 20(R)- and 20(S)-ginsenoside Rg3 in cholesterol-deprived medium. We found that ginsenoside Rh1 almost restored normal growth of worms in cholesterol-deprived medium in F1 generation. However, supplement of ginsenoside Rh2 caused a suppression of worm growths in cholesterol-deprived medium. In addition, CK and PPD also slightly restored normal growth of worms in cholesterol-deprived medium but PPT not. In experiments using ginsenoside epimers, supplement of 20(S)- but not 20(R)-ginsenoside Rg3 in cholesterol-deprived medium also almost restored worm growth. These results indicate that the absence or presence of carbohydrate component at backbone of ginsenoside, the number of carbohydrate attached at carbon-3, and the position of hydroxyl group at carbon-20 of ginsenoside might plays important roles in restoration of worm growth in cholesterol-deprived medium.

MicroRNAs are short, non-coding RNA molecules that regulate gene expression primarily by translational repression or by messenger RNA degradation. MicroRNAs play crucial roles in various biological processes. However, little is known regarding their role in obesity. We investigated differences of microRNA (miRNA) expression in liver tissue from diet-induced obese mice and potential effects of them on gene and protein expression. We used a miRNA microarray and quantitative RT-PCR to determine miRNA expression in murine liver tissue. Gene and protein expression were determined by qRT-PCR and Western blot analysis. Effects of miRNA by knock-down using RNAi or overexpression on putative target genes and/or proteins in a murine hepatic cell line were also investigated. MicroRNA array and qRT-PCR analsysis revealed that > 50 miRNAs were down- or upregulated more than 2-fold in the liver of diet-induced obese mice. While changes in expression of many genes were observed at the mRNA level, some were only altered at the protein level. Overexpression or knock-down of miR-107 in murine hepatic cells revealed that the expression of its putative target, fatty acid synthase, was dramatically decreased or increased, respectively. In conclusion, more than 50 hepatic miRNAs were dysregulated in diet-induced obese mice. Some of them regulate protein expression at translation level and others regulate mRNA expression at transcriptional level. MiR-107 is downregulated while FASN, a putative target of miR-107, was increased in diet-induced obese mice. These findings provide the evidence of the correlation of miRNAs and their targets in diet-induced obese mice.

Curcumin, a polyphenol found in the rhizomes of Curcuma longa , improves obesity-associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component β-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1α, GSK-3β, and Axin, components of the destruction complex targeting β-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells.

In this study, we identified various stilbenoids derived from Vitis coignetiae and investigated the protective effect of the main component, pterostilbene, against the inhibition of gap junctional intercellular communication (GJIC) induced by H(2)O(2) in WB-F344 rat liver epithelial cells. We analyzed seven kinds of stilbenoids, pterostilbene, astringin, piceid, vitisin, rhaponticin, resveratrol, and rhapontigenin, using DAD/UV HPLC. Total stilbenoid content was 127.37+/-19.29 mg/100g dry weight. Pretreatment with 0.5, 1.0, and 5.0 microM pterostilbene for 24h was shown to recover GJIC blocked by 500 microM H(2)O(2). Pretreatment with pterostilbene prevented the inhibition of GJIC via the down-regulation of connexin43 phosphorylation by the inactivation of ERK1/2 and p38 MAP kinase. Our results suggest that pterostilbene may be a functional chemopreventative agent and that dietary exposure of pterostilbene would be helpful for improving health.