Jarinyaporn Naowaboot

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.

Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High-Fat Diet/Streptozotocin-Induced Type 2 Diabetic Rats

Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright

Umbelliferone increases the expression of adipocyte-specific genes in 3T3-L1 adipocyte.

Umbelliferone (UMB), a natural product of coumarin family, has been shown to reduce blood glucose and to improve lipid profiles in streptozotocin (STZ)‐induced diabetic rats. Our objective was to examine the effect of UMB on adipogenesis by investigating its stimulatory effect on lipid accumulation and mRNA expression of adipogenic transcription factors and adipocyte‐specific genes in 3 T3‐L1 preadipocyte culture. An Oil Red O staining was used to monitor lipid accumulation, and we found that UMB treatment at concentration range of 10–100 μM significantly increased lipid accumulation of differentiating 3 T3‐L1 cells. At the molecular level of adipogenesis, we examined the mRNA expression of adipogenic transcription factors, peroxisome proliferator‐activated receptor γ, CCAAT/enhancer‐binding protein α, and sterol regulatory element‐binding protein 1c. Those transcription factors were increased by UMB at 10–100 μM. Interestingly, UMB also stimulated the mRNA expression of adipocyte‐specific genes, adipocyte fatty acid‐binding protein, lipoprotein lipase, fatty acid synthase, fatty acid translocase, and adiponectin. Our findings indicate that the stimulatory effect of UMB on adipocyte differentiation likely occurs through up‐regulation of adipogenic transcription factors and downstream adipocyte‐specific gene expression. Copyright

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.

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

Abstract 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.

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.

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.