Coffee consumption in aged mice increases energy production and decreases hepatic mTOR levels.

OBJECTIVE: Coffee, one of the world's most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. The aim of this study was to investigate the locomotor activity, energy metabolism, and lipid metabolism of aged (20-mo-old) mice given coffee. METHODS: Aged C57 BL/6 NCr mice were divided into three groups: controls that were not given coffee (n = 9), a group that received 0.1% caffeinated coffee (n = 9), and a group that received 0.1% decaffeinated coffee (n = 9). This regimen continued for 17 wk until mice reached the age of 24 mo. RESULTS: Regular and decaffeinated coffee consumption decreased plasma-free fatty acid levels, increased hepatic adenosine triphosphate content, and decreased total mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) protein content in the liver. However, no differences were found in the protein or activity levels of Akt, adenosine monophosphate-activated protein kinase (AMPK), p70 S6 kinase, or sterol regulatory element-binding protein 1, proteins that are upstream or downstream of the mTOR complex 1 (mTORC1)-related pathways. Regular coffee consumption increased food and water intake, locomotor activity, the volume of carbon dioxide production, and the respiration exchange ratio. CONCLUSION: Regular and decaffeinated coffee consumption decreased hepatic total mTOR and p-mTOR levels independently of Akt and AMPK pathways in aged mice. Because decreased mTORC1 activity is known to have antiaging effects, coffee consumption during old age may retard aging. Moreover, coffee consumption by the aged population had a positive effect on behavioral energy and lipid metabolism.

Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.

Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 µM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 µM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3ß4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 µM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 µM and 10-100 µM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

Ascorbic acid deficiency affects genes for oxidation-reduction and lipid metabolism in livers from SMP30/GNL knockout mice.

BACKGROUND: We sought to elucidate the effect of an ascorbic acid (AA) deficiency on gene expression, because the water soluble antioxidant AA is an important bioactive substance in vivo. METHODS: We performed microarray analyses of the transcriptome in the liver from senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which are unable to synthesize AA in vivo. RESULTS: Our microarray analysis revealed that the AA deficiency increased gene expression related to the oxidation-reduction process, i.e., the nuclear factor, erythroid derived 2, like 2 (Nrf2) gene, which is a reactive oxygen species-sensitive transcriptional factor. Moreover, this AA deficiency increased the expression of genes for lipid metabolism including the cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1), which is a late-limiting enzyme of the primary bile acid biosynthesis pathway. Although an AA deficiency increased the Cyp7a1 protein level, bile acid levels in the liver and gallbladder decreased. Since Cyp7a1 has a heme iron at the active site, AA must function as a reductant of the iron required for the continuous activation of Cyp7a1. CONCLUSIONS: This experimental evidence strongly supports a role for AA in the physiologic oxidation-reduction process and lipid metabolism including bile acid biosynthesis. GENERAL SIGNIFICANCE: Although many effects of AA supplementation have been reported, no microarray analysis of AA deficiency in vivo is available. Results from using this unique model of AA deficiency, the SMP30/GNL-KO mouse, now provide new information about formerly unknown AA functions that will implement further study of AA in vivo.

Ascorbic acid prevents protein oxidation in livers of senescence marker protein-30/gluconolactonase knockout mice.

AIM: Senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice are incapable of synthesizing L-ascorbic acid (AA) in vivo. As AA is known to be a water-soluble anti-oxidant, we assessed protein oxidation levels in livers from SMP30/GNL KO mice maintained in an AA-insufficient condition. METHODS: Livers were collected from male SMP30/GNL KO mice at the ages of 3, 6 and 12 months, and wild-type (WT) mice at the ages of 3, 6, 12 and 24 months. To assess protein oxidation, we measured the content of protein carbonyl, which is a major protein oxidation marker. AA levels were measured by 2,4-dinitrophenylhydrazine method using high-performance liquid chromatography. RESULTS: Livers of SMP30/GNL KO mice had just ∼5% as much AA as those of WT mice from 3 to 12 months-of-age. Protein carbonyl levels in livers from SMP30/GNL KO mice were a significant 1.8- to 2.3-fold higher than those from age-atched WT mice. To establish that the AA-insufficiency caused this difference, we added AA to some drinking water, and examined the effect on AA and protein carbonyl levels in livers from SMP30/GNL KO and WT mice. Livers from SMP30/GNL KO mice given extra AA had a significantly higher content than those from their deprived counterparts. Furthermore, protein carbonyl levels in livers from AA-supplemented SMP30/GNL KO mice were significantly lower than those from the SMP30/GNL KO mice without AA supplementation. However, added AA did not affect the protein carbonyl levels in WT mice. CONCLUSIONS: These results strongly suggest that AA plays an important role in preventing protein oxidation in vivo, thus enhancing overall health.

Mulberry leaf extract prevents amyloid beta-peptide fibril formation and neurotoxicity.

Mulberry leaf has been reported to possess medicinal properties, including hypoglycemic, hypotensive and diuretic effects. Little is known, however, about its medicinal properties for central nervous system disorders, including Alzheimer's disease. Accumulating evidence suggests that amyloid beta-peptide (1-42) plays an important role in the etiology of Alzheimer's disease. Here we show that mulberry leaf extract inhibits the amyloid beta-peptide (1-42) fibril formation by both the thioflavin T fluorescence assay and atomic force microscopy. Furthermore, mulberry leaf extract protected hippocampal neurons against amyloid beta-peptide (1-42)-induced cell death in a concentration-dependent manner. These results suggest that mulberry leaf extract provides a viable treatment for Alzheimer's disease through the inhibition of amyloid beta-peptide (1-42) fibril formation and attenuation of amyloid beta-peptide (1-42)-induced neurotoxicity.