## 2 Associations of Whole Grain-Specific Polyphenols with Cardiovascular and Metabolic Diseases
### Ferulic Acid (FA) and \(\gamma\)-Oryzanol (OZ)  
Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a derivative of hydroxycinnamic acid, a type of phenolic acid [31]. \(\gamma\)-oryzanol is a ferulic acid mixture in which triterpenors are bound to esterified ferulic acid [43]. Both compounds are representative bioactive substances of whole-grain rice bran [31; 32]. FA and OZ are effective in improving cardiovascular and metabolic diseases. The beneficial effects of FA and OZ on cardiovascular disease have been confirmed in animal models fed a HFD or high-fat, high-fructose diet (HFHF). In this model, FA and OZ decreased body weight, body fat, and blood lipid (TC, triglyceride [TG], low-density lipoprotein cholesterol [LDL-C], free fatty acid [FFA]) levels and increased high-densitylipoprotein cholesterol (HDL-C). It also inhibited the accumulation of TC and TG in the liver and aorta and improved markers of oxidative stress [glutathione peroxidase (GSH-Px), catalase (CAT), glutathione reductase (GR), paraoxonase (PON1), total antioxidant capacity (TAC), malondialdehydedehyde (MDA), lipid peroxide, vitamin E) and inflammation [tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)), interleukin -6 (IL-6), C-reactive protein (CRP)] [15; 18; 44; 45; 46; 47; 48]. In particular, OZ increased the fecal excretion of TC and inhibited lipid accumulation [46; 47]. In HepG2 cells, FA and OZ suppressed lipid accumulation by inhibiting the expression of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and diacylglycerol \(O\)-acyltransferase 1 (DGAT1) [18; 48]. Furthermore, the effects of FA and OZ on diabetes have been examined in various animal models. FA and OZ alleviate glucose intolerance and insulin resistance by decreasing glucose, glucose area under the curve (AUC), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) in animal models fed a HFHF diet or a high-carbohydrate, high-fat diet (HCHF) [15; 18; 48]. Blood glucose level and glucose intolerance were improved in _db/db_ mice and in a streptozotocin-induced diabetes rat model [45; 49]. These effects are presumed to be induced by FA and OZ, which activate glucokinase activity and increase hepatic glycogen synthesis by elevating AMP-activated protein kinase (AMPK) and Akt phosphorylation in the liver [45; 48]. FA has also been reported to regulate blood pressure. In HUVECs, FA treatment increased NO and cGMP levels by upregulating Aktl and eNOS expression and decreasing superoxide levels [38]. In spontaneously hypertensive rats (SHRs), FA inhibits the activity of an angiotensin-converting enzyme (ACE), which is responsible for the conversion of the inactive form of angiotensin I to the active vasoconstrictor angiotensin II [50]. In addition, FA improved NO bioavailability by reducing oxidative stress and the production of thromboxane B\({}_{2}\) (TXB\({}_{2}\)) [15; 51]. As a result, it was confirmed that FA has an antihypertensive effect by suppressing vasoconstriction via regulation of renin-angiotensin system (RAS) and endothelial function. In addition, FA and OZ reduce the thickness of arterial blood vessel walls in animal models; therefore, they are expected to prevent cardiovascular diseases and to have hypolipidemic, hypoglycemic, and blood pressure-lowering effects [15] (Table 1). \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline