Anti-Atherogenic, Anti-Inflammatory, and Anti-Hypertensive Effects of Peanuts Determined with In Vivo and In Vitro Models

Peanuts contain several cardiovascular beneficial nutrients and have been reported to reduce risk of cardiovascular diseases (CVD). Hypertension, hypercholesteremia, and atherosclerosis are leading causes of CVD. The first stage of atherosclerotic disease is accumulation of cholesteryl esters (CE) in arterial tissues. Hamsters are often utilized for CVD studies. A 24 wk study was conducted to characterize normal metabolism and age effects to include average concentrations of plasma, aortic cholesterols, and hepatic gene expression in male golden Syrian hamsters that consumed a standard breeding diet (STD). Plasma atherogenic index (AI) and CE did not change indicating no development of atherosclerosis with increased age. Consumption of STD diet did not have an apparent effect on hepatic genes encoding for inflammation and energy metabolism related to CVD.;A second study was conducted to evaluate effects of whole peanuts (WP) and peanut flour (PF) in high fat high cholesterol (HFHC) diets on development of atherosclerosis compared to a HFHC control (CON) diet. Results confirmed total plasma cholesterol (TPC) lowering properties of peanut component enriched diets and indicated cholesterol lowering effects independent of fatty acid content. Peanut component diets significantly reduced atherosclerosis as determined by arterial CE. Hepatic biochemical compounds indicated reduced oxidative stress, inflammation, and insulin resistance in hamsters that consumed peanut component diets compared to CON. Hepatic gene analysis indicated hamsters consuming peanut components had lower inflammatory mediator (ET-1) and more efficient sterol metabolism (CYP7A1 and ABCB11) compared to CON group. When consumed with HFHC diet, WP and PF protected against development of atherosclerosis by reducing inflammation, improving lipoprotein distribution, increasing fatty acid beta-oxidation, and upregulating excretion of cholesterol to bile.;A third study was performed to determine influence of WP and PF on reversion of atherosclerosis in hamsters after disease was induced by diet. Hamsters that consumed WP diet had significant reversion of TPC and no change in high density lipoprotein (HDL) cholesterol compared to diseased hamsters at 0 wk. Aortic total cholesterol (TC) and CE were significantly reversed after 6 wk of WP consumption and aortic TC was also significantly lower in the PF diet group. These data indicate significant reduction in early stage atherosclerotic development with consumption of peanuts. At 24 wk, hamsters that consumed the CON diet had increased TPC and non-HDL cholesterols as well as decreased HDL cholesterol compared to 0 wk. Hamsters that consumed WP or PF diet did not have a change of AI at wk 24 which indicates peanut components prevented the further development of atherosclerosis. These data, along with HDL cholesterol, suggest that WP and PF diet groups had a more efficient reverse cholesterol transport system, greater antioxidant status, and higher bile acid metabolism than the CON diet group.;PF is a valuable ingredient for product formulation and protein fortification. Bioactive peptides have been reported to act as antioxidants and reduce hypertension and atherosclerosis. Angiotensin I converting enzyme (ACE) regulates hypertension. Another blood pressure regulator is nitric oxide (NO), which also can act as an inflammatory signaling molecule and pro-oxidant in local tissues. PF was separated by pH and molecular weight (MW) and a portion of each fraction underwent enzymatic hydrolysis. Hydrolyzed MW fractions had the greatest ACE inhibition. The smallest MW digested peptide fraction had lowest inhibitory concentration and thus greatest potency. Peanut fractions significantly reduced local NO production in RAW 264.7 cells. These data suggest that peanut protein and peptide fractions protect against atherosclerosis because of anti-hypertensive and anti-inflammatory properties.