Effects of Red Rice Bran Extract on High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

Insulin resistance is a salient player in the pathogenesis of obesity and its related abnormal glucose-insulin homeostasis. Red rice bran extract (RRBE) demonstrates several bioactive phytochemicals with anti-diabetic properties. However, little is known about its molecular mechanisms. Therefore, the present study was designed to investigate the anti-insulin resistant mechanisms of RRBE in a model of high-fat diet (HFD)-induced insulin resistance. In this study, mice were randomly divided into four groups: low-fat diet with distilled water (Group L), HFD with distilled water (Group H), HFD with 0.5 g/kg RRBE, and HFD with 1 g/kg RRBE. Metabolic parameters, histological changes in the pancreas, and gene expression levels were evaluated after treating HFD-fed mice with RRBE for six weeks. Mice from Group H exhib-ited significantly higher blood glucose levels prior to and after an oral glucose tolerance test, fasting serum insulin levels, islet size, pancreatic insulin expression levels, and lower skeletal muscle insulin-degrading enzyme (IDE) expression levels compared to Group L. In contrast, these were all significantly restored in the RRBE-treated groups. Also, RRBE treatment was found to upregulate the expression of insulin receptor substrate (IRS) and glucose transporter (GLUT) genes in the adipose tissues and GLUT genes in the muscles and livers of HFD-fed mice. According to our results, RRBE may ameliorate abnormal glucose-insulin metabolism by modulating the expression of insulin, IDE, IRS, and GLUT genes in the major metabolic target tissues of mice after being fed with HFD.

Perinatal Taurine Supplementation Preserves the Benefits of Dynamic Exercise Training on Cardiovascular and Metabolic Functions and Prevents Organ Damage in Adult Male Exercised Rats.

Taurine supplementation is recommended during perinatal life to provide sufficient taurine for fetuses and newborns. Furthermore, perinatal taurine supplementation affects cardiovascular and metabolic functions in adult life. In adults, taurine supplementation is reported to improve exercise training. The present study explored the effects of perinatal taurine supplementation followed by dynamic exercise training on cardiovascular and metabolic functions in adult male rats. Pregnant Wistar rats were maintained on water containing or lacking 3% taurine from conception to weaning. After weaning, male offspring were fed normal rat chow and water throughout the study. At 4 weeks of age, the taurine-treated and taurine-untreated rats were subjected to either a swimming exercise protocol (10-30 min a day, 5 day a week) for 12 weeks (Ex and TEx) or remained sedentary (C and T). At 16 weeks of age, kidney weight, mean arterial pressure, baroreflex sensitivity, plasma leptin, plasma triglyceride, blood urea nitrogen, plasma creatinine, and SGOT were not significantly different among the four groups. Compared to the control, perinatal taurine supplementation alone did not significantly affect any of the measured cardiovascular and metabolic parameters. Exercise training significantly decreased bodyweight, heart rate, and visceral adipocyte size, irrespective of perinatal taurine supplementation, but increased SGPT and heart weight when compared to the control. However, the effect of exercise on SGPT, but not heart weight, was abolished by perinatal taurine supplementation. These data indicate that perinatal taurine supplementation not only preserves the beneficial effects of dynamic exercise training on cardiovascular and metabolic functions but also prevents exercise-induced organ damage in adult male rats.

Pluchea indica Leaf Extract Alleviates Dyslipidemia and Hepatic Steatosis by Modifying the Expression of Lipid Metabolism-Related Genes in Rats Fed a High Fat-High Fructose Diet.

This study evaluated the effect of Pluchea indica leaf extract (PIE) on dyslipidemia and lipid accumulation in the liver, emphasizing its molecular mechanisms in regulating lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40% lard and 20% fructose) for ten weeks. They were then divided into four groups receiving distilled water, PIE (100 or 300 mg/kg/d), and pioglitazone (10 mg/kg/d) for a further six weeks, during which the HFFD was continued. After the experiment, fasting blood glucose (FBG), oral glucose tolerance (OGT), serum insulin and leptin levels, lipid profiles, and hepatic triglyceride content were measured. Histological examination and expression levels of lipid metabolism-related genes in the liver were measured. HFFD-fed rats indicated a significantly increased FBG, serum leptin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores with impaired OGT and dyslipidemia compared to rats fed a normal diet. PIE significantly reduced FBG, serum leptin, and HOMA-IR scores and improved OGT. Additionally, PIE significantly improved dyslipidemia and decreased serum-free fatty acids and liver triglyceride content. Hepatic histological examination showed a marked reduction lipid accumulation in relation to HFFD controls. Interestingly, PIE significantly downregulated the expression of lipid synthesis-related genes and upregulated the expression of fatty-acid oxidation-related genes. In conclusion, PIE alleviates dyslipidemia and hepatic steatosis in HFFD rats plausibly by increasing insulin resistance and modifying the gene expression associated with lipid metabolism. PIE may be used as preventive nutrition for dyslipidemia and hepatic steatosis.

Raphanus sativus L. var. caudatus Extract Alleviates Impairment of Lipid and Glucose Homeostasis in Liver of High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

The present study investigated the activities of Raphanus sativus L. var. caudatus extract (RS) on abnormal lipid and glucose homeostasis in a high-fat diet (HFD)-induced obesity and insulin resistance in a mouse model. Institute of Cancer Research mice were rendered obese by 16-week HFD feeding. Obese mice were administered with 100 or 200 mg/kg/d RS orally during the last 8 weeks of diet feeding. Then, the biochemical parameters were determined. The gene and protein expressions regulating lipid and glucose homeostasis in the liver were measured. This study revealed that the state of hyperglycemia, hyperleptinemia, hyperinsulinemia, and hyperlipidemia was reduced after 8 weeks of RS treatment (100 or 200 mg/kg). Administration of RS also improved insulin sensitivity and increased serum adiponectin. The liver total cholesterol and triglyceride concentrations were decreased by both doses of RS. Notably, a decrease in the expression of liver-specific genes, including sterol regulatory element-binding protein 1c, fatty acid synthase, and acetyl-CoA carboxylase, was found in the RS-treated groups. Moreover, administration of RS showed a significant increase in the expression of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) proteins. These findings indicated that RS improved abnormal lipid and glucose homeostasis in the liver of obesity-associated insulin resistance mouse model, possibly through the stimulation of the AMPK/Sirt1 pathway.

Mentha cordifolia Leaf Extract Improves Hepatic Glucose and Lipid Metabolism in Obese Mice Fed with High-Fat Diet.

Mentha cordifolia (MC) is a popular herb used to flavor food in Thailand that exhibits several biological effects. The present study aimed to determine the role of MC in regulating glucose and lipid metabolism in mice fed a high-fat diet (HFD). ICR obese mice were fed an HFD (45 kcal% lard fat) for 12 weeks, with MC (100 and 200 mg/kg/d) treatment from Week 7. After treatment with MC for 6 weeks, mice showed significantly lower rates of hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increased amounts of serum adiponectin. Furthermore, in mice treated with MC, serum interleukin-6 and tumor necrosis factor alpha were significantly inhibited and liver histology results showed decreased lipid accumulation and liver triglyceride content vs. untreated mice. In addition, MC treatment was associated with smaller fat cells and lower gene expression of liver sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, and fatty acid synthase. However, MC treatment was associated with higher carnitine palmitoyltransferase 1a gene expression and significantly higher rates of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in liver, but lower levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. These results indicate MC regulates glucose and lipid metabolism in a HFD-induced obese mouse model, possibly via activation of AMPK signaling pathway.

Effect of Thunbergia laurifolia water extracts on hepatic insulin resistance in high-fat diet-induced obese mice

Objective: To examine the effect of water extract of Thunbergia laurifolia on hepatic insulin resistance in high-fat diet-induced obese mice. Methods: High-fat diet with 45 kcal％ lard fat was used for obesity induction in ICR mice. The mice were fed with high-fat diet for 16 weeks, and during the last 8 weeks, they were treated with 200 mg/kg/day of water extracts from Thunbergia laurifolia leaf, stem and flower. Serum biochemistry, liver histology, and protein expression were examined after the treatment. Results: Extracts from all of the three parts of Thunbergia laurifolia significantly alleviated hyperglycemia, hyperlipidemia, hyperinsulinemia, and hyperleptinemia. The stem and flower extracts improved glucose tolerance. All of the extracts significantly reduced serum TNFα and monocyte chemoattractant protein-1 levels. Liver weight, triglyceride levels, and lipid accumulation were also decreased. Moreover, hepatic glucose-6-phosphatase level was significantly decreased, while the levels of PPARα, phosphorylated AMPK, and phosphorylated Akt were significantly increased with treatment of Thunbergia laurifolia extracts. Conclusions: Thunbergia laurifolia extracts can ameliorate hepatic insulin resistance in high-fat diet-induced obese mice by improving glucose and lipid homeostasis, which may be associated with stimulating phosphorylation of AMPK and Akt pathways.

The Effect of Rice Bran Extract on Arterial Blood Pressure, Hepatic Steatosis, and Inflammation in Mice Fed with a High-Fat Diet.

BACKGROUND: Inflammation and hypertension are primary mechanisms involving in obesity-associated adverse effects of a high-fat diet. The aim of this study was to evaluate the effects of rice bran extract (RBE) on arterial blood pressure, hepatic steatosis, inflammation, and oxidative stress in high-fat diet (HFD)-induced obese mice. METHODS: Male ICR mice were divided into four groups, including a normal-diet control group, a high-fat diet (HFD) (60% kcal from fat) group, an HFD group treated with RBE (220 mg/kg/day), and an HFD group treated with 1100 mg/kg/day for eight weeks. Besides body weight and arterial blood pressure, we determined liver values of total cholesterol, triglyceride, as well as percent body fat, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), matrix metalloprotease-9 (MMP-9), cyclooxygenase-2 (COX-2), and mRNA endothelial nitric oxide synthase (eNOS). RESULTS: The HFD group had increased body weight, increased systolic and diastolic blood pressure, liver total cholesterol, triglyceride, NF-κB, COX-2 and MMP-9 protein levels, and decreased mRNA eNOS in the aorta. Mice of the HFD group receiving RBE had reduced diastolic blood pressure, as well as significantly decreased liver and serum TNF-α and MDA levels in the liver, and reduced NF-κB levels in both the liver and heart. CONCLUSIONS: These results demonstrate that RBE decreases diastolic blood pressure, the liver lipid droplet accumulation, liver and myocardial NF-κB, myocardial COX-2 and MMP-9 protein levels, and oxidative stress. Moreover, RBE may improve endothelial function and may alleviate adverse health effects associated with obesity including obesity-associated hypertension.

Corrigendum to "The Effect of Rice Bran Extract on Arterial Blood Pressure, Hepatic Steatosis, and Inflammation in Mice Fed with a High-Fat Diet".

[This corrects the article DOI: 10.1155/2020/8374287.].

Renoprotective effect of umbelliferone in high-fat diet/streptozotocin-induced type 2 diabetic rats

Objective: To evaluate the renoprotective effect of umbelliferone in high-fat diet/streptozotocin-induced type 2 diabetic rats. Methods: We established a streptozotocin-induced type 2 diabetic model in male Wistar rats. The rats were fed with high-fat diet (45 kcal％ lard fat) and injected with 35 mg/kg streptozotocin. Diabetic rats were treated with umbelliferone for 8 weeks. At the end of the experimental period, the serum and kidney were used for measuring biochemical parameters, protein expression and histological analysis. Results: After 8-week treatment, umbelliferone decreased fasting plasma glucose, concentrations of malondialdehyde and monocyte chemoattractant protein-1 in the plasma and tissues. It also significantly reduced serum creatinine, blood urea nitrogen, serum advanced glycation end products, as well as kidney weight in type 2 diabetic rats (P<0.05). Moreover, umbelliferone reduced the 24-h urine albumin, but increased 24-h urine creatinine excretion (P<0.05). In renal protein expression, umbelliferone decreased the levels of transforming growth factor-β1 and fibronectin while increasing the levels of superoxide dismutase and catalase (P<0.05). Renal histological examination revealed an enlarged glomerular size in diabetic rats, which was smaller in umbelliferone-treated diabetic rats. Conclusions: Umbelliferone alleviates renal dysfunction in diabetes via decreasing hyperglycemia, oxidative stress, inflammation and glycation.

Effects of Brassica oleracea extract on impaired glucose and lipid homeostasis in high-fat diet-induced obese mice

Objective: To examine the effect of Brassica oleracea extract (BO) on impaired glucose and lipid homeostasis in high-fat diet (HFD)-induced obese mice. Methods: Obesity of ICR mice was induced by feeding a HFD (45 kcal％ lard fat) for 16 weeks. During the last 8 weeks of study period, obese mice were additionally administered with BO (100 and 200 mg/kg/day). The metabolic parameters were determined. The gene expressions of hepatic lipogenesis were also studied. Results: After 8 weeks of treatment, BO (100 and 200 mg/kg) significantly reduced hyperglycemia and improved insulin sensitivity (P < 0.05). The serum lipid (total cholesterol, triglyceride, and non-esterified fatty acid) and hepatic triglyceride and non-esterified fatty acid were decreased (P < 0.05). The levels of insulin and leptin in serum were also decreased (P < 0.05). Moreover, the expressions of hepatic lipogenic genes including sterol regulatory element-binding protein 1c, fatty acid synthase, and acetyl-CoA carboxylase were decreased by BO treatment (P < 0.05). Conclusions: These results suggest that BO is a new therapeutic agent for improving the homeostasis of glucose and lipid in HFD-induced obese mice probably by suppression of lipogenic genes in liver tissue.

Vernonia cinerea water extract improves insulin resistance in high-fat diet-induced obese mice.

Vernonia cinerea (V cinerea) is a plant distributed in grassy areas in Southeast Asia and has several pharmacological effects, including antidiabetic activity. However, the information available regarding the effect of V cinerea on insulin resistance in high-fat diet (HFD)-induced obese mice is not yet determined. We hypothesized that V cinerea water extract (VC) improves insulin sensitivity in HFD-induced obese mice by modulating both phosphatidylinositol-3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) pathways in liver, skeletal muscle, and adipose tissue. Obesity was induced in mice from the Institute for Cancer Research by feeding an HFD 188.28 kJ (45 kcal % lard fat) for 12 weeks. During the last 6 weeks of the HFD, obese mice were treated with VC (250 and 500 mg/kg). We found that VC at both doses significantly reduced the hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia. Obese mice treated with VC could increase serum adiponectin but reduce the proinflammatory cytokines, tumor necrosis factor-α, and monocyte chemoattractant protein-1. The extracts decreased triglyceride storage in liver and skeletal muscle of obese mice. The average size of fat cells was smaller in VC-treated groups than that of the HFD group. The protein expressions of PI3K and AMPK pathways in liver, skeletal muscle, and adipose tissue were upregulated (increased phosphorylation of PI3K, protein kinase B, AMPK, and acetyl-CoA carboxylase) by VC treatment. Furthermore, the glucose transporter 4 was increased in muscle and adipose tissue in obese mice treated with VC. These data indicate that VC treatment stimulates phosphorylation of PI3K and AMPK pathways in liver, muscle, and adipose tissue. Stimulating these pathways may improve impaired glucose and lipid homeostasis in an HFD-induced obesity mouse model. Based on these findings, it appears that VC has potential as a functional food or therapeutic agent in management of insulin resistance related diseases, such as type 2 diabetes mellitus.

Effect of lemongrass water extract supplementation on atherogenic index and antioxidant status in rats.

Cymbopogon citratus (DC) Stapf., commonly known as lemongrass, possesses strong antioxidant and cardiotonic properties. Lemongrass water extract contains several polyphenolic compounds including gallic acid, isoquercetin, quercetin, rutin, catechin and tannic acid. Rutin, isoquercetin catechin and quercetin are the flavonoids most abundantly found in the extract. The extract significantly decreased total cholesterol, low-density lipoprotein and atherogenic index in rats after treatment (p < 0.05). Expression of genes and protein of sterol regulatory element binding protein-1c (SREBP1c) and HMG-CoA reductase (HMGR) was also lowered significantly in treated groups (p < 0.05). Moreover, serum antioxidant capacity increased in treated rats in comparison with untreated ones (p < 0.05) and was associated with decreased serum lipid peroxidation.

Anti-insulin resistant effect of ferulic acid on high fat diet-induced obese mice

To evaluate the insulin sensitivity action of ferulic acid (FA) in skeletal muscle and hypothalamus of high-fat diet (HFD)-induced obese mice.Methods: Obese mouse model was induced by HFD (45 kcal％ lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations.Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas (P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain (P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased (P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice.Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediatedvia modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.

Simvastatin potentiates doxorubicin activity against MCF-7 breast cancer cells.

Simvastatin is a low density lipoprotein-lowering drug that is widely used to prevent and treat cardiovascular disease by inhibiting the mevalonate pathway. Simvastatin also exhibits inhibitory effects on a number of types of cancer. In the present study, the effects of simvastatin on the activity of doxorubicin in the breast cancer MCF-7 cell line, and the mechanisms by which this interaction occurs were investigated. The effect of simvastatin and doxorubicin treatment, alone and in combination, on the growth of MCF-7 cells was evaluated by a sulforhodamine B and colony formation assay. To delineate the mechanisms of cell death, the following parameters were measured: Reactive oxygen species (ROS) production using the fluorescence probe dihydroethidium; caspase 3 activity by the fluorometry method; gene expression by quantitative polymerase chain reaction; and apoptotic- and proliferative-related protein levels by western blotting. MCF-7 cell proliferation was significantly suppressed by 24-48 h treatment with simvastatin alone. Doses of 10-50 µM simvastatin also enhanced the cytotoxicity of doxorubicin against MCF-7 cells in a dose-dependent manner, and decreased the colony-forming ability of MCF-7 cells. Simvastatin alone or in combination with doxorubicin significantly increased ROS levels. Combination treatment significantly decreased expression of the cell cycle regulatory protein Ras-related C3 botulinum toxin substrate 1 and numerous downstream proteins including cyclin-dependent kinase (Cdk) 2, Cdk4 and Cdk6. Additionally, simvastatin in combination with doxorubicin significantly induced expression of the cyclin-dependent kinase inhibitor p21, increased cytochrome c and caspase 3 expression and reduced cyclin D1 expression. In conclusion, simvastatin acts synergistically with the anticancer drug doxorubicin against MCF-7 cells, possibly through a downregulation of the cell cycle or induction of apoptosis. Although additional studies are required, simvastatin and doxorubicin combination may be a reasonable regimen for the treatment of breast cancer.

Bacopa monnieri (Brahmi) improved novel object recognition task and increased cerebral vesicular glutamate transporter type 3 in sub-chronic phencyclidine rat model of schizophrenia.

Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be a new treatment and prevention for cognitive deficits in schizophrenia by acting on cerebral VGLUT3 density. We aimed to study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups for cognitive enhancement effect study: Group 1, Control; Group 2, PCP administration; Group 3, PCP+Brahmi. A neuroprotective-effect study was also carried out. Rats were again assigned to three groups: Group 1, Control; Group 2, PCP administration; Group 3, Brahmi+PCP. Discrimination ratio (DR) representing cognitive ability was obtained from a novel object recognition task. VGLUT3 immunodensity was measured in the prefrontal cortex, striatum and cornu ammonis fields 1-3 (CA1-3) using immunohistochemistry. We found reduced DR in the PCP group, which occurred alongside VGLUT3 reduction in all brain areas. PCP+Brahmi showed higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex and striatum. Brahmi+PCP group showed a higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex, striatum and CA1-3. We concluded that reduced cerebral VGLUT3 was involved in cognitive deficit in PCP-administrated rats. Receiving Brahmi after PCP restored cognitive deficit by increasing VGLUT3 in the prefrontal cortex and striatum. Receiving Brahmi before PCP prevented cognitive impairment by elevating VGLUT3 in prefrontal cortex, striatum and CA1-3. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia.

Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice

Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities (AU)

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Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice.

Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities.

Ferulic acid improves lipid and glucose homeostasis in high-fat diet-induced obese mice.

Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high-fat diet (HFD)-induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level. Moreover, serum lipid level, and liver cholesterol and triglyceride accumulations were also reduced. The histological examination showed clear evidence of a decrease in the lipid droplets in liver tissues and smaller size of fat cells in the adipose tissue in the obese mice treated with FA. Interestingly, FA reduced the expression of hepatic lipogenic genes such as sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). It could also up-regulate hepatic carnitine palmitoyltransferase 1a (CPT1a) gene and peroxisome proliferator-activated receptor alpha (PPARα) proteins. The FA treatment was also found to suppress the protein expressions of hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxylase (PEPCK) and glucose-6-phosphatase (G6Pase). In conclusion, the findings of this study demonstrate that FA improves the glucose and lipid homeostasis in HFD-induced obese mice probably via modulating the expression of lipogenic and gluconeogenic genes in liver tissues.

Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

Objective: To investigate the effect of Rhinacanthus nasutus (R. nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice. Methods: Obesity was induced in the male ICR mice by feeding them a high-fat diet (60 kcal% fat) for 12 weeks. After the first six weeks of the diet, the obese mice were administered with the water extract of R. nasutus leaves at 250 and 500 mg/kg per day for the next six weeks. Subsequently, the blood glucose, lipid profiles, insulin, leptin, and adiponectin levels were measured. The liver and adipose tissues were excised for his-topathological examination and protein expression study. Results: After six weeks of the treatment, R. nasutus extract (at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level, improve the insulin sensitivity, decrease the serum leptin, and increase the serum adiponectin levels. The obese mice treated with R. nasutus were found to have a reduction in the increased lipid concen-trations in their serum and liver tissues. Moreover, treatment with R. nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues. Interestingly, the administration with R. nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha, fat cell adiponectin, and glucose transporter 4 proteins. Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

Pandanus amaryllifolius leaf extract increases insulin sensitivity in high-fat diet-induced obese mice

Objective: To examine the effect of Pandanus amaryllifolius (P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice. Methods: Obesity was induced in mice fed with high-fat diet (45%fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the 5th week of treatment, oral glucose tolerance test was conducted. After six weeks of treat-ment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination. Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues. Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.