Polyphenol-rich ethyl acetate fraction isolated from Molineria latifolia ameliorates insulin resistance in experimental diabetic rats via IRS1/AKT activation.

This study aimed to evaluate the effect of ethyl acetate fraction (EAF) isolated from Molineria latifolia rhizome as dietary interventions for type 2 diabetes mellitus (T2DM) and its underlying molecular mechanisms in vivo. Experimental rats were induced by high fat diet feeding coupled with combined exposure to streptozotocin and nicotinamide. Treatment with EAF improved glucose tolerance and lipid profiles, but the insulin secretion was unaltered. Gene expression analyses on insulin/adipocytokine signalling-related genes demonstrated tissue-specific transcriptional responses. In skeletal muscle and liver tissues, Socs1, Tnf and Mapk8 showed consistent transcript regulation. Furthermore, hepatic translational analyses revealed sensitization on proximal insulin signalling, with reduced expression of IRS1 serine phosphorylation, increased IRS1 tyrosine phosphorylation and increased phospho-AKT (Ser473). The present findings suggested that EAF exerted its effect by modulating insulin signalling, potentially via IRS1/AKT activation. The pharmacological attributes of EAF may implicate its potential therapeutic applications for diabetes management.

In utero Exposure to Germinated Brown Rice and Its GABA Extract Attenuates High-Fat-Diet-Induced Insulin Resistance in Rat Offspring.

BACKGROUND: Numerous studies have reported on the influence of diet on insulin resistance. Our study provides insight into the effect of germinated brown rice (GBR) and γ-aminobutyric acid (GABA) on early environment-driven programming and susceptibility to insulin resistance in rat offspring. METHODS: Male rat offspring from female Sprague-Dawley rats fed with a high-fat diet (HFD) alone, HFD + GBR, or HFD + GABA extract throughout pregnancy and lactation were weaned 4 weeks after delivery and followed up for 8 weeks. A biochemical analysis and an assessment of the hepatic expression of insulin signaling genes were performed. RESULTS: The results showed that intrauterine exposure to HFD caused metabolic perturbations in rat offspring which gravitated towards insulin resistance even though the rat offspring did not consume an HFD. GBR and GABA attenuated the HFD-induced changes by underlying regulation of the insulin signaling genes. CONCLUSIONS: The results suggest that intake of GBR and GABA during pregnancy and lactation can influence the programming of genes in rat offspring, thereby enhancing insulin sensitivity.

In utero exposure to germinated brown rice and its oryzanol-rich extract attenuated high fat diet-induced insulin resistance in F1 generation of rats.

BACKGROUND: The development of insulin resistance is multifactorial, with maternal pre- and postnatal nutrition having significant influences. In this regard, high fat diet (HFD) feeding in pregnancy has been shown to increase risks of metabolic diseases. Thus, we investigated the effects of supplementation of HFD with germinated brown rice (GBR) and GBR-derived gamma oryzanol-rich extract (OE) on insulin resistance and its epigenetic implications in pregnant rats and their offsprings. METHODS: Pregnant female Sprague dawley rats were fed with HFD alone, HFD + GBR or HFD + OE (100 or 200 mg/kg/day) throughout pregnancy and lactation. Their offsprings were weaned at 4 weeks post-delivery and were followed up until 8 weeks. Serum levels of adipokines were measured in dams and their offsprings, and global DNA methylation and histone acetylation patterns were estimated from the liver. RESULTS: The dams and offsprings of the GBR and OE groups had lower weight gain, glycemic response, 8-Iso prostaglandin, retinol binding protein 4 and fasting insulin, and elevated adiponectin levels compared with the HFD group. Fasting leptin levels were lower only in the GBR groups. Hepatic global DNA methylation was lower in the GBR groups while hepatic H4 acetylation was lower in both GBR and OE dams. In the offsprings, DNA methylation and H4 acetylation were only lower in the OE group. However, dams and offsprings of the GBR and OE groups had higher hepatic H3 acetylation. CONCLUSIONS: GBR and OE can be used as functional ingredients for the amelioration of HFD-induced epigeneticallymediated insulin resistance.

Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring.

BACKGROUND: Evidence suggests perinatal environments influence the risk of developing insulin resistance. OBJECTIVE: The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR) and GBR-derived gamma (γ) aminobutyric acid (GABA) extract on epigenetically mediated high fat diet-induced insulin resistance. DESIGN: Pregnant Sprague Dawley rats were fed high-fat diet (HFD), HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4) were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. RESULTS: Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. CONCLUSIONS: These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis.

Anticancer properties and phenolic contents of sequentially prepared extracts from different parts of selected medicinal plants indigenous to Malaysia.

Different parts of four edible medicinal plants (Casearia capitellata, Baccaurea motleyana, Phyllanthus pulcher and Strobilanthus crispus), indigenous to Malaysia, were extracted in different solvents, sequentially. The obtained 28 extracts were evaluated for their in vitro anticancer properties, using the MTS assay, on four human cancer cell lines: colon (HT-29), breast (MCF-7), prostate (DU-145) and lung (H460) cancers. The best anticancer activity was observed for the ethyl acetate (EA) extract of Casearia capitellata leaves on MCF-7 cell lines with IC50 2.0 µg/mL and its methanolic (MeOH) extract showed an outstanding activity against lung cancer cell lines. Dichloromethane (DCM) extract of Phyllanthus pulcher aerial parts showed the highest anticancer activity against DU-145 cell lines, while significant activity was exhibited by DCM extract of Phyllanthus pulcher roots on colon cancer cell lines with IC50 value of 8.1 µg/mL. Total phenolic content (TPC) ranged over 1-40 mg gallic acid equivalents (GAE)/g. For all the samples, highest yields of phenolics were obtained for MeOH extracts. Among all the extracts analyzed, the MeOH extracts of Strobilanthus crispus leaves exhibited the highest TPC than other samples (p < 0.05). This study shows that the nature of phenol determines its anticaner activity and not the number of phenols present.