Nil-Surin Rice Bran Hydrolysates Improve Lipid Metabolism and Hepatic Steatosis by Regulating Secretion of Adipokines and Expression of Lipid-Metabolism Genes.

Overconsumption of a high caloric diet is associated with metabolic disorders and a heightened risk of diabetes mellitus (DM), hepatic steatosis, and cardiovascular complications. The use of functional food has received much attention as a strategy in the prevention and treatment of metabolic disorders. This present study investigated whether Nil-Surin rice bran hydrolysates (NRH) could prevent or ameliorate the progression of metabolic disorders in rats in which insulin resistance (IR) was induced by a high fat-high fructose diet (HFFD). After 10 weeks of the HFFD, the rats showed elevated fasting blood glucose (FBG), impaired glucose tolerance, dysregulation of adipokine secretion, distorted lipid metabolism such as dyslipidemia, and increased intrahepatic fat accumulation. The IR was significantly attenuated by a daily dose of NRH (100 or 300 mg/kg/day). Doses of NRH rectified adipokine dysregulation by increasing serum adiponectin and improving hyperleptinemia. Interestingly, NRH decreased intrahepatic fat accumulation and improved dyslipidemia as shown by decreased levels of hepatic triglyceride (TG) and serum TG, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. In addition, a modulation of expression of lipid metabolism genes was observed: NRH prevented upregulation of the lipogenesis genes Srebf1 and Fasn. In addition, NRH enhanced the expression of fatty-acid oxidation genes, as evidenced by an increase of Ppara and Cpt1a when compared with the HFFD control group. The activities of NRH in the modulation of lipid metabolism and rectifying the dysregulation of adipokines may result in a decreased risk of DM and hepatic steatosis. Therefore, NRH may be beneficial in ameliorating metabolic disorders in the HFFD model.

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.

Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.

INTRODUCTION: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. METHODS: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RESULTS: RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-ß, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. CONCLUSION: RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

Cytotoxic flavonoids from the fruits of Derris indica.

Chemical investigation of the ethyl acetate extract from the fruits of Derris indica has led to the isolation of a new furanoflavonoid derivative, 4'-hydroxypinnatin (1), and five known compounds. Pinnatin (2) showed strong cytotoxicity against cholangiocarcinoma (KKU-100) and human hepatoma (HepG2) cell lines with IC50 values of 6.0 ± 2.7 and 9.0 ± 4.1 µg/ml, respectively, and showed maximal cell killing effect of about 88-90%. Flavone 5 exhibited the most cytotoxicity against KKU-100 but it showed moderate efficacy (Emax = 50.7%).

Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet.

A high carbohydrate-high fat (HCHF) diet causes insulin resistance (IR) and metabolic syndrome (MS). Rice bran has been demonstrated to have anti-dyslipidemic and anti-atherogenic properties in an obese mouse model. In the present study, we investigated the beneficial effects of rice bran protein hydrolysates (RBP) in HCHF-induced MS rats. After 12 weeks on this diet, the HCHF-fed group was divided into four subgroups, which were orally administered RBP 100 or 500 mg/kg, pioglitazone 10 mg/kg, or tap water for a further 6 weeks. Compared with normal diet control group, the MS rats had elevated levels of blood glucose, lipid, insulin, and HOMA-IR. Treatment with RBP significantly alleviated all those changes and restored insulin sensitivity. Additionally, RBP treatment increased adiponectin and suppressed leptin levels. Expression of Ppar-γ mRNA in adipose tissues was significantly increased whereas expression of lipogenic genes Srebf1 and Fasn was significantly decreased. Levels of mRNA of proinflammatory cytokines, Il-6, Tnf-α, Nos-2 and Mcp-1 were significantly decreased. In conclusion, the present findings support the consumption of RBP as a functional food to improve insulin resistance and to prevent the development of metabolic syndrome.

Rice bran protein hydrolysates prevented interleukin-6- and high glucose-induced insulin resistance in HepG2 cells.

Rice bran, which is a byproduct of rice milling process, contains various nutrients and biologically active compounds. Rice bran protein hydrolysates have various pharmacological activities such as antidiabetic and antidyslipidemic effects. However, there are limited studies about the mechanisms of rice bran protein hydrolysates (RBP) on insulin resistance and lipid metabolism. RBP used in this study were prepared from Thai Jasmine rice. When HepG2 cells were treated with IL-6, the IRS-1 expression and Akt phosphorylation were suppressed. This effect of IL-6 was prevented by RBP in association with inhibition of STAT3 phosphorylation and SOCS3 expression. RBP could increase the phospho-AMPK levels and inhibit IL-6- or high glucose-induced suppression of AMPK and Akt activation. High glucose-induced dysregulation of the expression of lipogenic genes, including SREBP-1c, FASN and CPT-1, was normalized by RBP treatment. Moreover, impaired glucose utilization in insulin resistant HepG2 cells was significantly alleviated by concurrent treatment with RBP. Our results suggested that RBP suppresses inflammatory cytokine signaling and activates AMPK, and thereby these effects may underlie the insulin sensitizing effect.