Studies on the Bioactive Natural Antioxidants From Oilseeds

Antioxidants are substances that when present at low concentrations compared to that of an oxidisable substrate significantly delays or inhibits oxidation of that substrate in food products or in living systems. Antioxidants are either endogenous to the body or derived from the diet. Several types of synthetic antioxidants like BHT, BHA, TBHQ etc. are also used in the food industry. However, findings and subsequent publicity has fostered significant consumer resistance to the use of synthetic food additives as antioxidants, colourants etc. and therefore food industry is in search of potential natural antioxidants from edible sources.The major dietary sources of antioxidant phytochemicals are cereals, legumes, fruits, vegetables, oilseeds, beverages, spices and herbs. In the present study, we have focused on rice bran and its byproducts. Rice is one of the oldest of food crops and has been a staple food in India from very ancient times. It is also the staple food for about 60% of the world's population. Rice bran is a byproduct of the rice milling industry and is a potential commercial source of a healthy edible oil viz. rice bran oil and a variety of bio-active phytochemicals.Defatted rice bran (DRB), a byproduct of rice bran oil extraction, is also a good source of insoluble dietary fiber, protein, phytic acid, inosito I, vitamin B and a variety of other phytochemicals. Though the antioxidant potential of DRB has been demonstrated, it still remained a relatively unexplored source material, which demanded further investigation especially with regard to its detailed phytochemical profile leading to practical application. The focus of the present investigation therefore has been on DRB primarily to establish its phytochemical status and feasibility of using it as a source of bio-active phytochemicals and natural antioxidants leading to value addition of DRB otherwise used as cattle feed. To gain a better understanding of the value of rice bran as a source of phytochemicals, five popular rice varieties of the region viz. PTB 50, PTB 39, PTB 38, JA Y A, and MO 10 and a wild variety (oryza nivara) that is mainly used for medicinal applications in traditional ayurvedic system were characterized along with commercial samples of rice bran. The present study also explains the feasibility of a process for the extraction, enrichment, and isolation of antioxidant compounds from DRB. The antioxidant potential of the extracts were evaluated both in bulk oils and in food relevant model emulsions, using standard in vitro models. Radical scavenging effects, indicative of possible biological effects, were also evaluated.

Adrenergic and muscarinic receptor subtypes functional regulation during diabetogenesis: Effect of curcumin and vitamin D3 pre-treatment

In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.