Analysis of astragaloside IV metabolism to cycloastragenol in human gut microorganism, bifidobacteria, and lactic acid bacteria.

This study investigated different gut bacteria in an anaerobic environment to identify specific candidates that could transform astragaloside IV (AIV) to cycloastragenol (CA). Two representative gut microbes, lactic acid bacteria (LAB) and bifidobacteria, could metabolize AIV to CA. Multiple screenings showed two metabolic pathways to metabolize AIV in two groups of bacteria. LAB metabolized AIV initiated by removing the C-6 glucose, whereas bifidobacteria indicated the initial removal of C-3 xylose. The final products differed between the two groups as bifidobacteria showed the production of CA, whereas LAB demonstrated preferential production of 20R, 24S-epoxy-6α, -16ß, -25-trihydroxy-9, -19-cycloartan-3-one (CA-2H).

A Review of Red Yeast Rice, a Traditional Fermented Food in Japan and East Asia: Its Characteristic Ingredients and Application in the Maintenance and Improvement of Health in Lipid Metabolism and the Circulatory System.

Red yeast rice has been used to produce alcoholic beverages and various fermented foods in China and Korea since ancient times; it has also been used to produce tofuyo (Okinawan-style fermented tofu) in Japan since the 18th century. Recently, monacolin K (lovastatin) which has cholesterol-lowering effects, was found in some strains of Monascus fungi. Since statins have been used world-wide as a cholesterol-lowering agent, processed foods containing natural statins are drawing attention as materials for primary prevention of life-style related diseases. In recent years, large-scale commercial production of red yeast rice using traditional solid-state fermentation has become possible, and various useful materials, including a variety of monascus pigments (polyketides) that spread as natural pigments, in addition to statins, are produced in the fermentation process. Red yeast rice has a lot of potential as a medicinal food. In this paper, we describe the history of red yeast rice as food, especially in Japan and East Asia, its production methods, use, and the ingredients with pharmacological activity. We then review evidence of the beneficial effects of red yeast rice in improving lipid metabolism and the circulatory system and its safety as a functional food.

Pharmacokinetic Study of Compound K in Japanese Subjects After Ingestion of Panax ginseng Fermented by Lactobacillus paracasei A221 Reveals Significant Increase of Absorption into Blood.

Compound K (CK) is a metabolite of a saponin in Panax ginseng, formed from ginsenoside, a triterpenoid glycoside, by human intestinal bacteria. Lactobacillus paracasei A221 isolated from fermented food can hydrolyze (deglycosylate) the main ginsenoside, ginsenoside Rb1, and generate CK. However, the pharmacokinetics of L. paracasei A221 fermented ginseng (FG) and nonfermented ginseng (NFG) have not been investigated so far. The aim of this study was to investigate the pharmacokinetics of CK after oral administration of single doses of FG and NFG in healthy Japanese adults. An open-label, randomized, single-dose, two-period, crossover study was conducted in 12 Japanese healthy volunteers (five men and seven women, aged 40-60 years). All subjects were equally allocated into two groups and administered tablets containing FG or NFG. Until 24 h after the administration, blood samples were sequentially collected, plasma concentrations of CK were measured, and the pharmacokinetic parameters were calculated. We also expected restoration of decreased testosterone level as one of the beneficial effects of FG and measured plasma total testosterone concentrations in male volunteers. The means of Tmax, Cmax, and area under the concentration-time curve (AUC) were significantly different between the two groups. In the FG group, AUC0-12h (ng h/mL) and AUC0-24h (ng h/mL) were, respectively, 58.3- and 17.5-fold higher than those in the NFG group. Moreover, mean testosterone concentration in the FG group significantly increased 24 h after administration. These results showed that the main ginsenoside metabolite of ginseng, CK, produced by L. paracasei A221 has potential utility in health maintenance in healthy middle-aged and old Japanese adults.

Preparation of (13)C-labeled ceramide by acetic acid bacteria and its incorporation in mice.

We prepared 2-hydroxypalmitoyl-sphinganine (dihydroceramide) labeled with a stable isotope by culturing acetic acid bacteria with (13)C-labeled acetic acid. The GC/MS spectrum of the trimethylsilyl derivative of (13)C-labeled dihydroceramide gave molecular ions with an increased mass of 12-17 Da over that of nonlabeled dihydroceramide. The fragment ions derived from both sphinganine base and 2-hydroxypalmitate were confirmed to be labeled with the stable isotope in the spectrum. Therefore, (13)C-labeled dihydroceramide can be an extremely useful tool for analyzing sphingolipid metabolism. The purified [(13)C]dihydroceramide was administered orally to mice for 12 days, and the total sphingoid base fractions in various tissues were analyzed by GC/MS. The spectrum patterns specific to (13)C-labeled sphingoids were detected in the tissues tested. Sphinganine pools in skin epidermis, liver, skeletal muscle, and synapse membrane in brain were replaced by [(13)C]sphinganine at about 4.5, 4.0, 1.0, and 0.3%, respectively. Moreover, about 1.0% of the sphingosine pool in the liver was replaced by [(13)C]sphingosine, implying that exogenous dihydroceramide can be converted to sphingosine. These results clearly indicate that ingested dihydroceramide can be incorporated into various tissues, including brain, and metabolized to other sphingolipids.

Effect of continuous ingestion of acetic Acid bacteria on memory retention and the synaptic function in aged rats.

We administered Acetobacter malorum NCI1683 (S24), containing a high concentration of dihydroceramide (7.2 mg/g of dry cell weight), consecutively to aged rats (male Crlj:Wistar rats, 22 months old). The ingestion of Acetobacter malorum for 89 d significantly extended the memory retention in passive avoidance tests, increased the release of acetylcholine with depolarization of brain synaptosomes and decreased the causative agents of neurodegenerative diseases in the cerebral cortices.

Acetic acid bacterial lipids improve cognitive function in dementia model rats.

Acetic acid bacteria, fermentative microorganisms of traditional foods, have unique alkali-stable lipids (ASL), such as dihydroceramide which is a precursor of sphingolipids. Sphingolipids are important components of the brain tissue. We examined the effect of oral administration of ASL in a rat model of dementia (7-week-old, male) with a basal forebrain lesion. In a water maze test, the dementia model rats demonstrated poor spatial orientation. The administration of ASL (165 or 1650 mg/kg of body weight per day, for 14 days) produced a significant improvement in learning ability in the dementia model rats. In vitro experiments showed ASL had the ability to promote neurite outgrowth in pheochromocytoma (PC12) cells. Among the ASL components, dihydroceramide has the most potent effect on the differentiation of PC12 cells. It is highly possible that oral administration of dihydroceramide-containing ASL reverses the decline in cognitive function in dementia.

Salicylic acid carboxyl methyltransferase induced in hairy root cultures of Atropa belladonna after treatment with exogeneously added salicylic acid.

In Atropa belladonna hairy roots, exogeneously added salicylic acid (SA) is converted to methyl salicylate (MSA) through the reaction, which might be catalysed by S-adenosyl-L-methionine: salicylic acid carboxyl methyltransferase (SAMT). Here we cloned a cDNA for A. belladonna SAMT (AbSAMT1), which consisted of 357 aa residues. It was expressed in E. coli, and the recombinant AbSAMT1 showed SAMT activity. When A. belladonna hairy roots were exposed to a high concentration of SA, AbSAMT1 mRNA begins to be expressed 12 h after the exposure, and steady expression continued over 144 h.