The suppression of the differentiation of adipocytes with Mallotus furetianus is regulated through the posttranslational modifications of C/EBPß.

Obesity is a major risk factor for various chronic diseases, especially lifestyle-related diseases. Therefore, finding a protective substance against obesity and elucidating its molecular mechanism is one of the most important problems for improving human health. In this study, we investigated the antiobesity effect of Mallotus furetianus extract (MFE). The aim of the study was to examine the in vivo and in vitro effects of MFE on lipid synthesis. We examined the effect using an in vivo experimental system with obesity model mice and an in vitro experimental system with 3T3-L1 preadipocytes. We found that the treatment of MFE significantly suppressed the increase in body weight and adipose tissue weight and morphological changes in the liver and adipose tissue of the obesity model mice. In the in vitro experimental system, we revealed that MFE treatment suppressed the expression of transcription factors such as C/EBPα, C/EBPß, and PPARγ, which are involved in the early differentiation of 3T3-L1 preadipocytes. As a result, the ability to synthesize triacylglycerol was suppressed. An interesting finding in this study was the clarification that MFE decreases the expression of C/EBPß through post-translation modifications (PTMs), followed by the transcriptional suppression of PPAR𝛾 and C/EBP𝛼.

Kaempferia galanga L. extract and its main component, ethyl p-methoxycinnamate, inhibit the proliferation of Ehrlich ascites tumor cells by suppressing TFAM expression.

Kaempferia galanga L. shows anti-cancer effects; however, the underling mechanism remains unclear. In this study, we explored the underlying mechanism of the anti-cancer effects of Kaempferia galanga L. Kaempferia galanga L. rhizome extracts (KGEs) suppressed Ehrlich ascites tumor cell (EATC) proliferation by inhibiting S-phase progression. The main component of KGE is ethyl p-methoxycinnamate (EMC), which exhibits the same anti-proliferative effect as KGE. Furthermore, EMC induced the downregulation of cyclin D1 and upregulation of p21. EMC also decreased the expression of mitochondrial transcription factor A (TFAM) but did not significantly change mitochondrial DNA copy number and membrane potential. Phosphorylation at Ser62 of c-Myc, a transcription factor of TFAM, was decreased by EMC treatment, which might be due to the suppression of H-ras expression. These results indicate that EMC is the active compound responsible for the anti-cancer effect of KGE and suppresses EATC proliferation by regulating the protein expression of cyclin D1 and p21; TFAM may also regulate the expression of these genes. In addition, we investigated the anticancer effects of KGE and EMC in vivo using EATC bearing mice. The volume of ascites fluid was significantly increased by intraperitoneal administration of EATC. However, the increase in the volume of ascites fluid was suppressed by oral administration of EMC and KGE. This study provides novel insights into the association between the anti-cancer effects of natural compounds and TFAM, indicating that TFAM might be a potential therapeutic target.

Glyoxylic Acid, an α-Keto Acid Metabolite Derived from Glycine, Promotes Myogenesis in C2C12 Cells.

α-Keto acids may help prevent malnutrition in patients with chronic kidney disease (CKD), who consume protein-restricted diets, because they serve as amino acid sources without producing nitrogenous waste compounds. However, the physiological roles of α-keto acids, especially those derived from non-essential amino acids, remain unclear. In this study, we examined the effect of glyoxylic acid (GA), an α-keto acid metabolite derived from glycine, on myogenesis in C2C12 cells. Differentiation and mitochondrial biogenesis were used as myogenesis indicators. Treatment with GA for 6 d resulted in an increase in the expression of differentiation markers (myosin heavy chain II and myogenic regulatory factors), mitochondrial biogenesis, and intracellular amounts of amino acids (glycine, serine, and alanine) and their metabolites (citric acid and succinic acid). In addition, GA treatment suppressed the 2.5-µM dexamethasone (Dex)-induced increase in mRNA levels of ubiquitin ligases (Trim63 and Fbxo32), muscle atrophy markers. These results indicate that GA promotes myogenesis, suppresses Dex-induced muscle atrophy, and is metabolized to amino acids in muscle cells. Although further in vivo experiments are needed, GA may be a beneficial nutrient for ameliorating the loss of muscle mass, strength, and function in patients with CKD on a strict dietary protein restriction.

Phosphodiesterase 4 mRNA Level Suppression is Important for Extract of Black Carrot to Protect Against Hepatic Injury Induced by Ethanol.

Excessive alcohol use often results in alcoholic liver disease (ALD). An early change in the liver due to excessive drinking is hepatic steatosis, which may ultimately progress to hepatitis, liver fibrosis, cirrhosis, and liver cancer. Among these debilitating processes, hepatic steatosis is reversible with the appropriate treatment. Therefore, it is important to find treatments and foods that reverse hepatic steatosis. Black carrot has antioxidant and anti-inflammatory effects. In this study, we examined the effectiveness of black carrot extract (BCE) on hepatic steatosis in in vivo and in vitro ethanol-induced liver injury models. For the in vivo experiments, serum aminotransferase activities enhanced by ethanol- and carbon tetrachloride were significantly suppressed by the BCE diet. Furthermore, morphological changes in the liver hepatic steatosis and fibrosis were observed in the in vivo ethanol-induced liver injury model, however, BCE feeding resulted in the recovery to an almost normal liver morphology. In the in vitro experiments, ethanol treatment induced reactive oxygen species (ROS) levels in hepatocytes at 9 h. Conversely, ROS production was suppressed to control levels and hepatic steatosis was suppressed when hepatocyte culture with ethanol were treated with BCE. Furthermore, we investigated enzyme activities, enzyme protein levels, and messenger RNA levels of alcohol dehydrogenase (ADH), cytochrome p450 2E1 (CYP2E1), and aldehyde dehydrogenase (ALDH) using enzyme assays, western blot, and quantitative reverse transcription-polymerase chain reaction analyses. We found that the activities of ADH, CYP2E1, and ALDH were regulated through the cAMP-PKA pathway at different levels, namely, translational, posttranslational, and transcriptional levels, respectively. The most interesting finding of this study is that BCE increases cAMP levels by suppressing the Pde4b mRNA and PDE4b protein levels in ethanol-treated hepatocytes, suggesting that BCE may prevent ALD.

Black carrot extract protects against hepatic injury through epigenetic modifications.

We studied the epigenetic regulation of how black carrot extract (BCE) protects against ethanol-induced hepatic damage. We have shown that the butanol-extracted fraction of BCE (BCE-BuOH) increased intracellular cyclic adenosine monophosphate (cAMP) levels by suppressing the expression of phosphodiesterase 4b (PDE4b); however, the detailed mechanism remains to be elucidated. We focused on changes in histone modifications involved in the suppression of pde4 expression. The methylation level of histone H3 lysine 9 (H3K9), which regulates gene expression of PDE4b, decreased after treatment with 100 mM ethanol but was significantly increased by treatment with 400 µg/ml BCE-BuOH. In contrast, ethanol induced an increase in H3K9 acetylation. However, treatment with BCE-BuOH inhibited the increase in acetylation through an increase in Sirtuin 1 (Sirt1), a histone deacetylase. Furthermore, BCE-BuOH treatment increased the level of methionine adenosyltransferase (MAT) 2a mRNA and increased intracellular S-adenosylmethionine. The present results indicate that BCE-BuOH is useful for protection against alcohol-induced hepatic injury. PRACTICAL APPLICATIONS: We have reported that black carrot extract (BCE) suppressed liver steatosis and liver fibrosis on a rat alcoholic liver disease model. The results from this study have shown that BCE regulated the alcoholic-induced hepatic injury at the level of epigenetic modifications. These results suggested that BCE is useful for protection against alcoholic-induced hepatic injury.

Ursolic acid improves the indoxyl sulfate-induced impairment of mitochondrial biogenesis in C2C12 cells.

BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) have a high concentration of uremic toxins in their blood and often experience muscle atrophy. Indoxyl sulfate (IS) is a uremic toxin produced by tryptophan metabolism. Although an elevated IS level may induce muscle dysfunction, the effect of IS on physiological concentration has not been elucidated. Additionally, the effects of ursolic acid (UA) on muscle hypertrophy have been reported in healthy models; however, it is unclear whether UA ameliorates muscle dysfunction associated with chronic diseases, such as CKD. Thus, this study aimed to investigate whether UA can improve the IS-induced impairment of mitochondrial biogenesis. MATERIALS/METHODS: C2C12 cells were incubated with or without IS (0.1 mM) and UA (1 or 2 µM) to elucidate the physiological effect of UA on CKD-related mitochondrial dysfunction and its related mechanisms using real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. RESULTS: IS suppressed the expression of differentiation marker genes without decreasing cell viability. IS decreased the mitochondrial DNA copy number and ATP levels by downregulating the genes pertaining to mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Sirt1, and Mef2c), fusion (Mfn1 and Mfn2), oxidative phosphorylation (Cycs and Atp5b), and fatty acid oxidation (Pdk4, Acadm, Cpt1b, and Cd36). Furthermore, IS increased the intracellular mRNA and secretory protein levels of interleukin (IL)-6. Finally, UA ameliorated the IS-induced impairment in C2C12 cells. CONCLUSIONS: Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.

Carob pod polyphenols suppress the differentiation of adipocytes through posttranscriptional regulation of C/EBPß.

Obesity is a major risk factor for various chronic diseases such as diabetes, cardiovascular disease, and cancer; hence, there is an urgent need for an effective strategy to prevent this disorder. Currently, the anti-obesity effects of food ingredients are drawing attention. Therefore, we focused on carob, which has high antioxidant capacity and various physiological effects, and examined its anti-obesity effect. Carob is cultivated in the Mediterranean region, and its roasted powder is used as a substitute for cocoa powder. We investigated the effect of carob pod polyphenols (CPPs) on suppressing increases in adipose tissue weight and adipocyte hypertrophy in high fat diet-induced obesity model mice, and the mechanism by which CPPs inhibit the differentiation of 3T3-L1 preadipocytes into adipocytes in vitro. In an in vivo experimental system, we revealed that CPPs significantly suppressed the increase in adipose tissue weight and adipocyte hypertrophy. Moreover, in an in vitro experimental system, CPPs acted at the early stage of differentiation of 3T3-L1 preadipocytes and suppressed cell proliferation because of differentiation induction. They also suppressed the expression of transcription factors involved in adipocyte differentiation, thereby reducing triacylglycerol synthesis ability and triglycerol (TG) accumulation. Notably, CPPs regulated CCAAT/enhancer binding protein (C/EBP)ß, which is expressed at the early stage of differentiation, at the posttranscriptional level. These results demonstrate that CPPs suppress the differentiation of adipocytes through the posttranscriptional regulation of C/EBPß and may serve as an effective anti-obesity compound.

Lignin-derived low-molecular-weight oxidized lignophenol stimulates AMP-activated protein kinase and suppresses renal inflammation and interstitial fibrosis in high fat diet-fed mice.

Excess weight and obesity increase the risk of developing major risk factors for chronic kidney disease. Lignin comprises 20%-30% of the global plant biomass; however, it is not well utilized because of its resistance to chemical and biological degradation. We investigated whether low-molecular-weight oxidized lignophenol (LOLP), a lignin derivative, could alter inflammation and fibrosis in the kidneys of a high-fat diet (HFD)-fed mice. Male mice were divided into three treatment groups: HFD; HFD +0.3% LOLP; and HFD +0.6% LOLP. The control mice (Cont) were fed a low-fat diet. Macrophage kinetics, the degree of fibrosis, the extent of phosphorylation of AMP-activated protein kinase (AMPK), and mRNA expression of proinflammatory mediators in the kidneys were examined. The number of macrophages, the percentage of fibrotic area, and the mRNA expression of proinflammatory markers, TNF-α and Ccl2, and a marker of fibrosis, TGF-ß, were significantly higher in the kidneys of mice in the HFD group than those in the Cont group. Conversely, treatment with 0.6% LOLP for 8 weeks significantly suppressed the degree of macrophage infiltration, interstitial fibrotic area, and the increased mRNA expression of proinflammatory and fibrosis markers induced by HFD. In conclusion, LOLP suppressed macrophage infiltration and the increase in fibrotic area, and upregulated AMPK phosphorylation in the kidneys of HFD-fed mice; thus, it may ameliorate HFD-induced kidney injury.

Maternal quercetin intake during lactation attenuates renal inflammation and modulates autophagy flux in high-fructose-diet-fed female rat offspring exposed to maternal malnutrition.

Maternal restriction of dietary proteins during pregnancy and lactation is known to induce renal disease in later life. High fructose intake causes metabolic syndrome, which results in an increased risk of chronic kidney disease development. We investigated whether quercetin intake during lactation affects high-fructose-diet-induced inflammation and autophagy flux in the kidneys of high-fructose-diet-fed adult female offspring exposed to maternal normal-protein (NP) or low-protein (LP) diets. Pregnant Wistar rats received diets containing 20% (NP) or 8% (LP) casein, and 0 or 0.2% quercetin containing NP diets (NP/NP or NP/NPQ) in experiment (Expt.) 1 and 0 or 0.2% quercetin containing LP diets (LP/LP or LP/LPQ) in Expt. 2 during lactation. At weaning, pups that received a diet of distilled water (Wa) or 10% fructose solution (Fr) were divided into six groups: NP/NP/Wa, NP/NP/Fr, NP/NPQ/Fr in Expt. 1, and LP/LP/Wa, LP/LP/Fr, LP/LPQ/Fr in Expt. 2. At week 12, macrophage infiltration, mRNA levels of TNF-α and IL-6, and markers of autophagy flux in the kidneys of male offspring were examined. We found that macrophage number and, TNF-α and IL-6 mRNA levels increased in the kidneys of the NP/NP/Fr or LP/LP/Fr, respectively. Conversely, macrophage number and IL-6 levels in the NP/NPQ/Fr or LP/LPQ/Fr decreased. LC3B-II levels were downregulated in the NP/NP/Fr or LP/LP/Fr rats. In contrast, LC3B-II levels were upregulated, while p62 levels were downregulated in the NP/NPQ/Fr and LP/LPQ/Fr rats. In conclusion, maternal quercetin intake during lactation may cause long-term alterations in inflammation and autophagy flux in the kidneys of high-fructose-diet-fed adult female offspring.

The Validity of Estimated Dietary Amino Acid and Protein Values via the Amino Acid Composition Table 2015.

The amino acid composition table (AACT) plays a pivotal role in examining the association between dietary amino acid intake and physical conditions. The updated version, AACT 2015, has been markedly expanded; however, most additions are not based on analytical values. The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) recommend that protein contents be calculated as the sum of amino acid residues (PROTCAA). However, due to the lack of a validated AACT, protein content calculated as reference nitrogen multiplied by a nitrogen to protein conversion factor (PROTRN) is still commonly used. In this study, validity of the estimated dietary amino acid values via the AACT 2015 was examined by comparing differences between the estimated and analytical values, for 14 consecutive days' meals provided in an elder care facility. There were no major differences between the analytical and estimated values over the 14 d; however, noticeable daily differences sometimes emerged. These results indicate that the AACT 2015 may contain accidental errors, but allows the estimation of habitual amino acid intake. In the near future, PROTCAA will become the international standard. It will be necessary to convert PROTRN values to PROTCAA to refer to past reports and data; we have determined a correction factor (0.896) for this conversion.

Maternal green tea polyphenol intake during lactation attenuates kidney injury in high-fat-diet-fed male offspring programmed by maternal protein restriction in rats.

Maternal malnutrition is known to increase the risk of obesity in offspring. We investigated whether green tea extract (GTE) intake during lactation affects obesity-related fibrosis and inflammation in the kidney of high-fat-diet-fed adult offspring of protein-restricted-diet-fed dams during pregnancy and lactation. Pregnant Wistar rats received diets containing 20% (normal-protein, NP) or 8% (low-protein, LP) casein, and they received 0%-, 0.12%- or 0.24%-GTE-containing LP diets (LP/LP, LP/LGT and LP/HGT, respectively) during lactation. At weaning, the pups that received a diet providing 13% (normal-fat, NF) or 45% (high-fat, HF) energy from fat were divided into five groups: NP/NP/NF, LP/LP/NF, LP/LP/HF, LP/LGT/HF and LP/HGT/HF. At week 45, the degree of fibrosis; macrophage infiltration; protein expression levels of TGF-ß; and mRNA levels of TNF-α, DNMT, UHRF1 and histone lysine methyltransferase (G9a) in the kidneys of male offspring were examined. The area of fibrosis and TGF-ßlevels increased in the LP/LP/HF group. Conversely, the fibrotic areas and TGF-ß levels in the LP/HGT/HF group decreased (33% and 31%, respectively) compared with those in the LP/LP/HF group. The number of macrophages and mRNA levels of TNF-α in the LP/HGT/HF group decreased (34% and 29%, respectively) compared with those in the LP/LP/HF group. DNMT1, UHRF1 and G9a mRNA levels in the LP/HGT/HF group decreased compared with those in the LP/LP/HF group. In conclusion, GTE intake during lactation attenuated tubulointerstitial fibrosis and macrophage infiltration by down-regulating epigenetic modulators such as DNMT1, UHRF1 and G9a in the kidney of HF-diet-fed adult offspring programmed by maternal protein restriction.

Total synthesis of pectenotoxin-2.

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

p-terphenyl derivatives from the mushroom Thelephora aurantiotincta suppress the proliferation of human hepatocellular carcinoma cells via iron chelation.

A novel 2',3'-dihydroxy-p-terphenyl derivative, thelephantin O (TO), which has cancer-selective cytotoxicity, was isolated. This study investigated the underlying basis of the cytotoxicity of 2',3'-dihydroxy-p-terphenyl compounds in view of their ability to chelate metal ions. FeCl(2) significantly reduced TO-induced cytotoxicity, whereas several other salts of transition metals and alkaline-earth metals did not. A structure-activity relationship study using newly synthesized p-terphenyl derivatives revealed that o-dihydroxy substitution of the central benzene ring was necessary for both the cytotoxicity and Fe(2+) chelation of the compounds. Real-time PCR array and cell cycle analysis revealed that the TO-induced cytotoxicity was attributed to cell cycle arrest at the G1 phase via well-known cell cycle-mediated genes. The TO-induced changes in the cell cycle and gene expression were completely reversed by the addition of FeCl(2). Thus, it was concluded that Fe(2+) chelation occurs upstream in the pivotal pathway of 2',3'-dihydroxy-p-terphenyl-induced inhibition of cancer cell proliferation.

Total synthesis of thelephantin O, vialinin A/terrestrin A, and terrestrins B-D.

The first total synthesis of natural, unsymmetrical 2',3'-diacyloxy-p-terphenyls, thelephantin O (1) and terrestrins C and D (2 and 3, respectively), was achieved via a practical route which was also applicable to the synthesis of the symmetrical diesters vialinin A/terrestrin A (4) and terrestrin B (5). Compounds 1-5 exhibited cytotoxicity against cancer cells (HepG2 and Caco2) with IC(50) values of 13.6-26.7 µmol/L.

Anticancer activities of thelephantin O and vialinin A isolated from Thelephora aurantiotincta.

Thelephora aurantiotincta is an edible mushroom belonging to the genus Thelephora; it grows in symbiosis with pine trees. Recently, phytochemical investigations have revealed that the genus Thelephora is an abundant source of p-terphenyl derivatives. However, their bioactivity has not yet been well characterized. In screening for natural materials with anticancer activity, a T. aurantiotincta ethanol extract (TAE) was found to decrease cell viability in human hepatocellular carcinoma cells (HepG2). In this study, a new p-terphenyl derivative, thelephantin O, and a known compound, vialinin A, were isolated as the principal bioactive components of TAE. These compounds decreased cell viability in HepG2 and human colonic carcinoma cells (Caco2), but not in noncancerous human hepatocytes. This is the first report of the isolation from T. aurantiotincta of selective cytotoxic agents against cancer cells.

Effect of lignin-derived lignophenols on vascular oxidative stress and inflammation in streptozotocin-induced diabetic rats.

Lignophenols (LP) are the derivatives of native lignin, which is an abundant organic polymer in the plant kingdom. This study investigated whether LP can attenuate vascular oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. The diabetic rats induced by a single intravenous injection of STZ were randomly divided into two groups fed either 0 or 1.0% LP-containing diet. After 5 weeks of treatment, the superoxide (O(2)(-)) production, mRNA expression levels of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase subunits, monocyte chemoattractant protein-1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2), and protein expression level of inducible nitric oxide synthase (iNOS) were examined in the aorta of vehicle-injected control and diabetic rats treated with or without LP. The increased O(2)(-) production and mRNA expression levels of NAD(P)H oxidase subunits Nox4 and p47phox were found to be significantly reduced in the aorta of diabetic rats treated with LP. The mRNA expression of MCP-1 and CCR2, and the protein expression of iNOS were found to be increased in the aorta of untreated diabetic rats, whereas these levels were significantly lower in the LP-treated group. These findings suggest that LP could attenuate vascular oxidative stress and/or inflammation via inhibition of NAD(P)H oxidase. This may lead to an improvement in the vascular impairment of diabetes.

Lignophenols decrease oleate-induced apolipoprotein-B secretion in HepG2 cells.

Lignin is one of the components in the plant cell wall, after cellulose, making up 20-30% of the global plant biomass. Lignophenols (LPs) are derivatives of lignin with high phenolic function and antioxidant properties. However, their medicinal property is not well characterised. Apolipoprotein-B (apo-B) is an essential component in very low-density lipoprotein, and high levels of serum apolipoprotein-B (apo-B) are a major factor for coronary heart disease. In this study, we examined the effect of lignophenols on apo-B secretion in HepG2 cells. HepG2 cells were treated with varying concentrations of LPs and 0.8 mm sodium oleate. LPs decreased oleate-induced apo-B secretion in a dose-dependent manner. LPs also decreased oleate-induced microsomal triglyceride transfer protein (MTTP) mRNA expression and cellular total cholesterol, suggesting that lipid bioavailability and lipidation of lipoprotein are likely involved in the decreased secretion of apo-B. Furthermore, LPs decreased oleate-induced mature sterol regulatory element binding protein 2 (SREBP-2), a transcription factor that activates cholesterol biosynthesis. This is the first study to show that LPs can decrease oleate-induced apo-B secretion in HepG2 cells. The modulations of MTTP mRNA expression, cellular total cholesterol metabolism and mature SREBP-2 expression may be important factors in the regulation of apo-B secretion by LPs.

Anti-obesity effect of Blumea balsamifera extract in 3T3-L1 preadipocytes and adipocytes.

Obesity, the leading metabolic disease in the world, is a serious health problem in industrialized countries. We investigated the anti-obesity effect of Blumea balsamifera extract on adipocyte differentiation of 3T3-L1 preadipocytes and anti-obesity effect of 3T3-L1 adipocytes. We found that treatment with an extract of Blumea balsamifera suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and adipocytes. Furthermore, Blumea balsamifera extract brought significant attenuation of expressions of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT element binding protein (C/EBPs) and leptin, however, induced up-regulation of adiponectin at the protein level in 3T3-L1 preadipocytes and adipocytes. These results suggest that Blumea balsamifera extract may block adipogenesis, at least in part, by decreasing key adipogenic transcription factors in 3T3-L1 preadipocytes and may have antiatherogenic, anti-inflammatory, and antidiabetic effects through up-regulation of adiponectin in 3T3-L1 adipocytes.

Lignin-derived lignophenols attenuate oxidative and inflammatory damage to the kidney in streptozotocin-induced diabetic rats.

This study investigated the effects of lignin-derived lignophenols (LPs) on the oxidative stress and infiltration of macrophages in the kidney of streptozotocin (STZ)-induced diabetic rats. The diabetic rats were divided into four groups with 0%, 0.11%, 0.33% and 1.0% LP diets. The vehicle-injected controls were given a commercial diet. At 5 weeks, superoxide (O(2)(-)) production, macrophage kinetics, the degree of fibrosis in glomeruli and mRNA expression for monocyte chemoattractant protein-1 (MCP-1) were examined. The NADPH-stimulated O(2)(-) levels in the kidney of the diabetic rats treated with 1.0% LP were significantly lower than those in untreated diabetic rats. The number of macrophages, levels of MCP-1 mRNA expression and degree of glomerular fibrosis increased in untreated LP and these levels were significantly lower in 1.0%LP-treated rats. The results suggested that LPs suppress the excess oxidative stress, the infiltration and activation of macrophages and the glomerular expansion in STZ-induced diabetic kidneys.

Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells.

Anticarcinogenic effects attributed to phytochemicals may be based on synergistic, additive, or antagonistic interactions of many compounds. In our previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba tea and believe in the synergic effects of jujuba and tea for better health. We therefore investigated the effects of CHCl(3)-F and green tea extract (GTE), and their underlying mechanisms of action in HepG2 cells. Our results showed that GTE enhanced the effect of CHCl(3)-F on cell viability in HepG2 cells, without cytotoxicity in rat hepatocytes, which was used as a normal cell model. Furthermore, combination of CHCl(3)-F and GTE caused an effect on G1 phase arrest but not on apoptosis. Interestingly, the mechanism of the G1 arrest was associated, not with an increase in p27(Kip1) levels and the hypohosphorylation of Rb, which are pathways used by CHCl(3)-F on G1 arrest in HepG2 cells, but with increases in p53 and p21(Waf1/Cip1) levels, and a decrease in cyclin E levels. Collectively, our findings suggest that combination of CHCl(3)-F and GTE produces an enhanced cell growth inhibition effect, and that the resultant G1 arrest was caused via a different mechanism as that of CHCl(3)-F treatment alone.