Effects of Nutraceuticals and Botanicals on Macrophage Cholesterol Efflux: Implications for Atherosclerosis

To date, the literature on high-density lipoprotein (HDL) levels as an inverse risk factor for atherosclerosis has mainly been observational, and it is likely that the metabolism and function of HDL is a more significant determinant of cardiovascular disease. As an example, as cholesterol is effluxed out of macrophages and carried to the liver via HDL for excretion, reduced cholesterol efflux can result in increased cholesterol accumulation. In terms of atherosclerosis risk, increasing cholesterol efflux is theoretically a strategy that can be considered as the groundwork of cardiovascular disease treatment and prevention. However, until now, there has not been a pharmaceutical agent that has effectively increased reverse cholesterol transport (RCT) at all steps of the process. Here is a review of the research on natural compounds present in edible foods and their observed in vitro and in vivo (and even ex vivo) effects on the first step of RCT: macrophage cholesterol efflux. The findings here are preliminary and contradictory, making it hard to translate the evidence on most of these naturally occurring agents into clinical applications

γ-Tocopherol Accelerated Sodium Excretion in a Dose-Dependent Manner in Rats with a High Sodium Intake

We have previously reported that γ-tocopherol (γ-Toc) displays a natriuretic potency in rats fed a NaCl diet and administered 20 mg γ-Toc. In this study, we investigated whether γ-Toc has natriuretic potency at a dose lower or higher than 20 mg in rats given a NaCl diet. Male rats were fed a control diet or a NaCl diet and administered either placebo or 10, 20 or 40 mg of γ-Toc. The rat urine was collected for 24 hours (divided into 6 hour periods) and the 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) level, the sodium excretion content, and the urine volume were determined. The 24-hour γ-CEHC and sodium levels in the urine of the NaCl groups given 20 mg or 40 mg γ-Toc were significantly higher than those in the placebo group. The peak levels of urine sodium and γ-CEHC in the NaCl group given 40 mg γ-Toc appeared at 0–6 h, which was a more rapid increase than that seen in the group given 20 mg γ-Toc. The 24-hour urine volumes of the NaCl groups given 10 and 20 mg γ-Toc were significantly higher than the urine volume of the placebo group. Our findings suggested that γ-Toc increased sodium excretion in a dose-dependent manner in rats fed a NaCl diet. Moreover, a high dose of γ-Toc may accelerate its metabolism and cause an increase in the rate of sodium excretion

Suppressive Effect of Shiitake Extract on Plasma Ethanol Elevation

Alcohol is usually consumed with meals, but chronic consumption is a leading cause of alcoholic liver diseases. We investigated if shiitake extracts with a high lentinic acid content (Shiitake-H) and without lentinic acid (Shiitake-N) could suppress the elevation in plasma ethanol concentrations by accelerating ethanol metabolism and preventing ethanol absorption from the gut. Shiitake-H and Shiitake-N suppressed the elevation in concentrations of ethanol and acetaldehyde in plasma, and promoted the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver. However, these effects of Shiitake-H were more prominent than those of Shiitake-N. Furthermore, Shitake-H promoted ADH and ALDH activities in the stomach. We also examined the change in plasma ethanol concentration by injecting Shiitake-H or Shiitake-N into the ligated loop of the stomach or jejunum together with an ethanol solution. Shiitake-H suppressed the absorption of ethanol from the stomach and jejunum. In conclusion, Shiitake-H accelerates ethanol metabolism in the stomach and liver and inhibits ethanol absorption in the stomach and jejunum indicating that lentinic acid is a functional component in shiitake

Sulfuric Odor Precursor S-Allyl-l-Cysteine Sulfoxide in Garlic Induces Detoxifying Enzymes and Prevents Hepatic Injury

S-Allyl-l-cysteine sulfoxide (ACSO) is a precursor of garlic-odor compounds like diallyl disulfide (DADS) and diallyl trisulfide (DATS) known as bioactive components. ACSO has suitable properties as a food material because it is water-soluble, odorless, tasteless and rich in bulbs of fresh garlic. The present study was conducted to examine the preventive effect of ACSO on hepatic injury induced by CCl4 in rats. ACSO, its analogs and garlic-odor compounds were each orally administered via gavage for five consecutive days before inducing hepatic injury. Then, biomarkers for hepatic injury and antioxidative state were measured. Furthermore, we evaluated the absorption and metabolism of ACSO in the small intestine of rats and NF-E2-related factor 2 (Nrf2) nuclear translocation by ACSO using HepG2 cells. As a result, ACSO, DADS and DATS significantly suppressed the increases in biomarkers for hepatic injury such as the activities of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH), and decreases in antioxidative potency such as glutathione (GSH) level and the activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx). We also found ACSO was absorbed into the portal vein from the small intestine but partially metabolized to DADS probably in the small intestine. In in vitro study, ACSO induced Nrf2 nuclear translocation in HepG2 cells, which is recognized as an initial trigger to induce antioxidative and detoxifying enzymes. Taken together, orally administered ACSO probably reached the liver and induced antioxidative and detoxifying enzymes by Nrf2 nuclear translocation, resulting in prevention of hepatic injury. DADS produced by the metabolism of ACSO in the small intestine might also have contributed to the prevention of hepatic injury. These results suggest potential use of ACSO in functional foods that prevent hepatic injury and other diseases caused by reactive oxygen species (ROS)

γ-Tocopherol Enhances Sodium Excretion as a Natriuretic Hormone Precursor

Endogenous natriuretic factors are believed to be responsible for extracellular fluid homeostasis in mammals. A new endogenous natriuretic factor, Loma Linda University-alpha (LLU-α) has recently been proven to be a 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), which is a metabolite of γ-tocopherol (γ-Toc). The purpose of this study was to investigate whether γ-Toc could accelerate sodium excretion into rat urine as a natriuretic hormone precursor. Male SD strain rats were divided into two groups ; one was a control diet group, while the other was a high NaCl group (50 g/kg diet). Next, the two groups were each subdivided into two groups consisting of a placebo group and a γ-Toc group. After the oral administration of one experimental dose of 20 mg γ-Toc or placebo, rat urine was collected at 6 h intervals for 24 h, and then the urine volume, sodium and potassium and γ-CEHC content were determined. γ-Toc increased in the urine volume of the high-NaCl intake group. The sodium excretion in the high-NaCl group given γ-Toc was 8.29±2.20 g, while in the control group given γ-Toc it was 6.24±1.49 g fr om 12-18 h. In contrast, the potassium excretion in the rat urine did not change in any of the groups. Our findings suggested that γ-Toc accelerates the degree of sodium excretion in rats with a high sodium intake

<i>S</i>-Allyl-L-cysteine sulfoxide, a garlic odor precursor, suppresses elevation in blood ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from gut

<p>Alcoholic beverages are enjoyed together with meals worldwide, but their excessive intake is associated with an increased risk of various diseases. We investigated whether <i>S</i>-allyl-L-cysteine sulfoxide (ACSO), a sulfuric odor precursor of garlic, suppresses elevation in plasma ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from the gut in rats. ACSO and garlic extract with a high ACSO content (Garlic-H) suppressed elevation in concentrations of ethanol and acetaldehyde in plasma and promoted the activities of alcohol dehydrogenase and aldehyde dehydrogenase. However, ACSO and Garlic-H did not affect plasma acetate so much. Furthermore, we examined the change in plasma ethanol concentration by injecting ACSO or Garlic-H into the ligated stomach or jejunum together with ethanol solution. ACSO and Garlic-H suppressed the absorption of ethanol from the stomach and jejunum<b>,</b> but suppression in the jejunum was less than in the stomach. In conclusion, ACSO inhibits ethanol absorption and accelerates ethanol metabolism.</p> <p>A garlic odor precursor suppresses blood ethanol elevation.</p