Chia Ju Chang

Myricetin Increases Hepatic Peroxisome Proliferator-Activated Receptor α Protein Expression and Decreases Plasma Lipids and Adiposity in Rats

The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of myricetin. Myricetin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3T3-L1 adipocytes. The high-fat diet (HFD)-fed rats were dosed orally with myricetin or fenofibrate, once daily for eight weeks. Myricetin (300 mg kg−1 per day) displayed similar characteristics to fenofibrate (100 mg kg−1 per day) in reducing lowered body weight (BW) gain, visceral fat-pad weights and plasma lipid levels of HFD-fed rats. Myricetin also reduced the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplets accumulation and epididymal adipocyte size in HFD-fed rats. Myricetin and fenofibrate reversed the HFD-induced down-regulation of the hepatic peroxisome proliferator activated receptor (PPAR)α. HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase and cytochrome P450 isoform 4A1 were up-regulated by myricetin and fenofibrate. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD-fed rats were lowered by myricetin and fenofibrate. These results suggest that myricetin suppressed BW gain and body fat accumulation by increasing the fatty acid oxidation, which was likely mediated via up-regulation of PPARα and down-regulation of SREBP expressions in the liver of HFD-fed rats.

The Ethanol Extract of Zingiber zerumbet Attenuates Streptozotocin-Induced Diabetic Nephropathy in Rats

The ethanol extract from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) has been indicated to possess an insulin-like property by ameliorating hyperglycemia in diabetes. We aimed to investigate whether EEZZR exerts an ameliorative effect on renal damage in diabetes induced by streptozotocin (STZ). Diabetic rats were treated orally with EEZZR (200 and 300 mg kg−1 per day) or metformin (100 mg kg−1 per day) for 8 weeks. The plasma glucose, creatinine, and blood urea nitrogen as well as urine protein levels and the ratio of kidney weight to body weight were significantly elevated in diabetic rats. EEZZR displayed similar characteristics to those of metformin in reducing hyperglycemia and renal dysfunction in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following the treatment with EEZZR. In addition, the protein expressions of renal nephrin and podocin in diabetic rats were significantly increased following the treatment with EEZZR. The AMP-activated protein kinase (AMPK) protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. EEZZR treatment significantly rescued the AMPK phosphorylation compared to nontreated diabetic group. This study suggested that the renoprotective effects of EEZZR may be similar, with the action of metformin, to the prevention of AMPK dephosphorylation and upregulate the expressions of renal nephrin and podocin.

Beneficial Effect of Traditional Chinese Medicinal Formula Danggui-Shaoyao-San on Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Diabetic Rats

The present study was undertaken to characterize the effects of Danggui-Shaoyao-San (DSS), a famous traditional Chinese medicine formula consisting of six herbal medicines, on diabetic nephropathy. Streptozotocin-induced diabetic rats were orally administrated DSS (2.8 g kg−1 per day) for 12 consecutive weeks. DSS partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-hour urinary albumin excretion rate, and creatinine clearance as well as the kidney hypertrophy (kidney weight/body weight ratio) and glomerular mesangial matrix expansion were ameliorated after 12 weeks of DSS treatment. The increased expression of nuclear factor-κB as well as transforming growth factor-β 1 and the progressive accumulation of type IV collagen in kidney of diabetic rats were also attenuated by DSS. Not only the elevated levels of advanced glycation end products (AGEs) and N ε-(carboxymethyl)lysine but also the higher levels of lipid peroxidation products in kidney of diabetic rats were ameliorated by DSS. Decreased activity of superoxide diamutase and glutathione peroxidase in kidney of diabetic rats was enhanced by DSS. These data demonstrated that the renoprotective effects of DSS in STZ-diabetic rats not only were attributable to regulate plasma glucose to attenuate AGEs expression in diabetic glomeruli but also likely reflected its antioxidant activity.

Emodin, a Naturally Occurring Anthraquinone Derivative, Ameliorates Dyslipidemia by Activating AMP-Activated Protein Kinase in High-Fat-Diet-Fed Rats

The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of emodin on high-fat diet (HFD)-induced obese rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed HFD for two weeks, Wistar rats were dosed orally with emodin (40 and 80 mg kg−1) or pioglitazone (20 mg kg−1), once daily for eight weeks. Emodin (80 mg kg−1 per day) displayed similar characteristics to pioglitazone (20 mg kg−1 per day) in reducing body weight gain, plasma lipid levels as well as coronary artery risk index and atherogenic index of HFD-fed rats. Emodin also caused dose related reductions in the hepatic triglyceride and cholesterol contents and lowered hepatic lipid droplets accumulation in HFD-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in hepatocytes of HFD-fed rats. Our findings suggest emodin could attenuate lipid accumulation by decreasing lipogenesis and increasing mitochondrial fatty acid β-oxidation mediated by activation of the AMPK signaling pathway.

Regulation of lipid disorders by ethanol extracts from Zingiber zerumbet in high-fat diet-induced rats.

The aim of this study was to investigate the antihyperlipidaemic effects of the ethanol extract of Zingiber zerumbet (L) Smith (EEZZ). After being fed a high-fat diet (HFD) for 2weeks, rats were dosed orally with EEZZ (100, 200 or 300mg/kg) or fenofibrate (100mg/kg) once daily for 8weeks. EEZZ (300mg/kg/day) produced effects similar to fenofibrate in reducing body weight gain, visceral fat-pad weights and plasma lipid levels. EEZZ caused reductions in hepatic triglyceride and cholesterol content, and lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes. HFD-induced reductions in the hepatic proteins of peroxisome proliferator-activated receptor (PPAR) α, acyl-CoA oxidase (ACO) and cytochrome P450 isoform 4A1 (CYP4A1) were reversed by EEZZ. These results suggest that EEZZ reduced the accumulation of visceral fat and improved hyperlipidaemia in HFD-fed rats by increasing fatty acid oxidation, an effect which is likely to be mediated via up-regulation of hepatic PPARα.

Emodin protects against high-fat diet-induced obesity via regulation of AMP-activated protein kinase pathways in white adipose tissue.

Emodin is an active herbal component traditionally used in China for treating a variety of diseases. The aim of this study was to examine the effect of emodin on the reducing lipid accumulation in white adipose tissue of high-fat diet-fed rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed a high-fat diet for two weeks, rats were dosed orally with emodin (20, 40, 80 mg/kg/day) or pioglitazone (20 mg/kg/day), once daily for eight weeks. Changes in body weight, feeding pattern, serum lipids, coronary artery risk index, and atherogenic index were investigated. Subcutaneous white adipose tissues were isolated for pathology histology and Western blot analyses. Changes of triglyceride accumulation in differentiated 3 T3-L1 adipocytes were also investigated. Emodin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3 T3-L1 adipocytes. Emodin (80 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing body weight gain and plasma lipid levels as well as the coronary artery risk and atherogenic indices of high-fat diet-fed rats. Emodin also caused dose related reductions in epididymal white adipose tissue sizes in high-fat diet-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase and its primary downstream targeting enzyme, acetyl-CoA carboxylase, upregulated gene expression of carnitine palmitoyl transferase 1, and downregulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the epididymal white adipose tissue of high-fat diet-fed rats. Our findings suggest that emodin could attenuate lipid accumulation in white adipose tissue through AMP-activated protein kinase activation.

6-Gingerol Inhibits Rosiglitazone-Induced Adipogenesis in 3T3-L1 Adipocytes

We investigated the effects of 6‐gingerol ((S)‐5‐hydroxy‐1‐(4‐hydroxy‐3‐methoxyphenyl)‐3‐decanone) on the inhibition of rosiglitazone (RGZ)‐induced adipogenesis in 3T3‐L1 cells. The morphological changes were photographed based on staining lipid accumulation by Oil‐Red O in RGZ (1 µmol/l)‐treated 3T3‐L1 cells without or with various concentrations of 6‐gingerol on differentiation day 8. Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction. Differentiated cells were lysed to detect mRNA and protein levels of adipocyte‐specific transcription factors by real‐time reverse transcription‐polymerase chain reaction and Western blot analysis, respectively. 6‐gingerol (50 µmol/l) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ‐induced adipocyte differentiation in 3T3‐L1 cells. The triglyceride accumulation induced by RGZ in differentiated 3T3‐L1 cells was also reduced by 6‐gingerol (50 µmol/l). Treatment of differentiated 3T3‐L1 cells with 6‐gingerol (50 µmol/l) antagonized RGZ‐induced gene expression of peroxisome proliferator‐activated receptor (PPAR)γ and CCAAT/enhancer‐binding protein α. Additionally, the increased levels of mRNA and protein in adipocyte‐specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3‐L1 cells were decreased upon treatment with 6‐gingerol. Our data suggests that 6‐gingerol may be beneficial in obesity, by reducing adipogenesis partly through the down‐regulating PPARγ activity. Copyright

Absence of Genotoxic and Mutagenic Effects of Zingiber zerumbet (L.) Smith (Zingiberaceae) Extract

The present study evaluated the potential genotoxicity of the ethanol extracts from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) using a standard battery of tests. Chemical analysis with liquid chromatography-tandem mass spectrometry revealed that EEZZR contained Zerumbone (200.3 ± 0.37 μg/g) and 6-gingerol (102.5 ± 0.28 μg/g). There were no increases in the number of revertant colonies with EEZZR at concentrations of 150–5000 μg per plate, regardless of the metabolic activation system (S-9 mix) used in the histidine-dependent auxotrophic mutants of Salmonella typhimurium (strains TA97, TA98, TA100, TA102, and TA1535) compared to the vehicle control. Furthermore, EEZZR at doses of 150–5000 μg mL−1 did not increase the number of structural aberrations in Chinese hamster lung cells in the presence or absence of S-9 mix. An oral administration of EEZZR to ICR mice, with doses of up to 2000 mg/kg, caused no significant increases in the number of micronucleated polychromatic erythrocytes (MNPCEs) and mean ratio of polychromatic erythrocytes to total erythrocytes. Lastly, RZZEE did not increase the incidence of MNPCEs in bone marrow. Based on these findings, it may be concluded that the use of EEZZR in traditional medicine poses no risk of genotoxicity.

Angelica Acutiloba Root Alleviates Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Diabetic Rats

Angelica acutiloba root, a Japanese species of Dong quai being cultivated in Hualien County in eastern Taiwan, is used primarily for gynecological disorders in women. Increasing evidence indicates that advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic nephropathy. We investigated whether A. acutiloba root is beneficial in the amelioration of AGE-mediated renal injury in a diabetic rat model. Streptozotocin (STZ)-diabetic rats were treated orally with A. acutiloba root extract (AARE) [50, 100, 200 mg/(kg × day)] for 8 wk. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for enzyme immunoassay, pathology histology, immunohistochemistry, and Western blot analyses. Polyphenolic compounds and flavonoids were abundant in AARE. AARE [200 mg/(kg × day)] partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-h urinary albumin excretion rate, creatinine clearance, and glomerular mesangial matrix expansion were ameliorated by AARE treatment. The increased expression of nuclear factor-κB, transforming growth factor-β(1), and the progressive accumulation of fibronectin in kidney of diabetic rats were attenuated by AARE treatment. AARE treatment ameliorated the elevated levels of advanced glycation end products (AGEs) and mitochondrial thiobarbituric acid-reactive substance, as well as the elevated levels of Nε-(carboxymethyl)lysine and receptors for AGEs in kidneys of diabetic rats. The results show that A. acutiloba root has an anti-diabetic property that involves antihyperglycemia accompanied by amelioration of glycation-mediated renal damage.

Cassia tora (Leguminosae) seed extract alleviates high-fat diet-induced nonalcoholic fatty liver.

The aim of this study was to examine the effects of Cassia tora seeds on high-fat diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract (CSEE) (100, 200, or 300mg/kg) once daily for 8weeks. CSEE induced dose-dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation. Furthermore, CSEE treatment improved HFD-induced hepatic histological lesions. CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated the gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the livers of HFD-fed rats. AMPK inhibition by compound C retarded CSEE-induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin. Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK-dependent signaling pathway. Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity-related non-alcoholic fatty liver disease.