Risk of cardiovascular disease is suppressed by dietary supplementation with protamine and chitooligosaccharide in Sprague-Dawley rats.

Protamine from salmon spermaries is a novel dietary protein. Chitooligosaccharide (COS) is an oligosaccharide derived from chitin or chitosan, a long-chain polymer, by chemical or enzymatic hydrolysis. These two compounds are known to enhance lipid metabolism by interrupting the digestion and absorption of fat in the body. Cardiovascular disease (CVD) refers to any type of specific disease that affects the heart and circulatory system. Dyslipidemia, a condition involving high levels of low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, is generally known to be a primary cause of CVD development. The risk of CVD is usually associated with the atherogenic index (AI) and cardiac risk factor (CRF). The CVD risk is also closely associated with serum levels of total cholesterol (T-CHO), LDL cholesterol and HDL cholesterol. In the present study, we evaluated alterations in serum lipid contents following the administration of protamine, COS and mixtures of these two compounds to male Sprague-Dawley (SD) rats, and their ability to reduce CVD risk. Based on the results of a serum lipid assay, protamine, COS and their mixtures were found to significantly reduce AI, CRF and CVD risk by decreasing serum levels of TG, T-CHO and LDL cholesterol and increasing serum HDL cholesterol levels. By contrast, TG and T-CHO concentrations in feces were markedly increased. Accumulation of lipids in the liver tissues of the SD rats fed high-fat diets was also inhibited by the intake of protamine and COS. Our findings suggest that protamine, COS and combinations of the two compounds may be used as a dietary therapy for preventing CVD due to their suppressive effects on hyperlipidemia and hypercholesterolemia.

Improvement of high-fat diet-induced obesity by a mixture of red grape extract, soy isoflavone and L-carnitine: implications in cardiovascular and non-alcoholic fatty liver diseases.

In the present study, we examined the effect of a mixture of dietary components, including red grape extract, soy isoflavone and L-carnitine (RISC), on obesity. RISC substantially inhibited high-fat diet (HFD)-induced increase in body weight in a dose-dependent manner in C57BL/6 mice. The amount of subcutaneous and mesenteric fat was also significantly decreased by RISC treatment in HFD-fed C57BL/6 mice, whereas epididymal fat was not affected. Moreover, HFD-induced plasma leptin levels were down-regulated by RISC treatment. In these mice, RISC treatment significantly increased the plasma level of high density lipoprotein cholesterol without affecting the level of low density lipoprotein cholesterol and triglycerides. In addition, HFD-induced increase in liver weight and lipid accumulation in liver was significantly suppressed by RISC treatment in C57BL/6mice. Plasma level of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase was also inhibited by RISC treatment. These results demonstrate that RISC suppresses HFD-induced obesity and suggest that RISC supplementation might be a promising adjuvant therapy for the treatment of obesity and its complications, such as cardiovascular and non-alcoholic fatty liver diseases.

A combination of grape extract, green tea extract and L-carnitine improves high-fat diet-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease in mice.

To develop a therapeutic agent for obesity-related metabolic disorders, a mixture of dietary components was prepared, including grape extract, green tea extract and l-carnitine (RGTC), and its effects on obesity, hyperlipidemia and non-alcoholic fatty liver disease examined. The RGTC dramatically inhibited the high-fat diet (HFD)-induced increase in body weight and fat in C57BL/6 mice, whereas food consumption was not affected by RGTC treatment. The RGTC also concentration-dependently suppressed the HFD-induced increase in plasma lipids, such as low-density lipoprotein cholesterol and triglycerides. In addition, increases in liver weight and liver steatosis were returned to normal by RGTC treatment in HFD-fed C57BL/6 mice. The plasma levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were also significantly down-regulated by RGTC treatment. These results suggest that RGTC suppressed HFD-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease, suggesting that RGTC supplementation might be a promising adjuvant therapy for the treatment of these metabolic disorders.

A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study.

A combination of green tea extract and l-theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies. In this randomized, double-blind, placebo-controlled study, the effect of LGNC-07 on memory and attention in subjects with mild cognitive impairment (MCI) was investigated. Ninety-one MCI subjects whose Mini Mental State Examination-K (MMSE-K) scores were between 21 and 26 and who were in either stage 2 or 3 on the Global Deterioration Scale were enrolled in this study. The treatment group (13 men, 32 women; 57.58 ± 9.45 years) took 1,680 mg of LGNC-07, and the placebo group (12 men, 34 women; 56.28 ± 9.92 years) received an equivalent amount of maltodextrin and lactose for 16 weeks. Neuropsychological tests (Rey-Kim memory test and Stroop color-word test) and electroencephalography were conducted to evaluate the effect of LGNC-07 on memory and attention. Further analyses were stratified by baseline severity to evaluate treatment response on the degree of impairment (MMSE-K 21-23 and 24-26). LGNC-07 led to improvements in memory by marginally increasing delayed recognition in the Rey-Kim memory test (P = .0572). Stratified analyses showed that LGNC-07 improved memory and selective attention by significantly increasing the Rey-Kim memory quotient and word reading in the subjects with MMSE-K scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Electroencephalograms were recorded in 24 randomly selected subjects hourly for 3 hours in eye-open, eye-closed, and reading states after a single dose of LGNC-07 (LGNC-07, n = 12; placebo, n = 12). Brain theta waves, an indicator of cognitive alertness, were increased significantly in the temporal, frontal, parietal, and occipital areas after 3 hours in the eye-open and reading states. Therefore, this study suggests that LGNC-07 has potential as an intervention for cognitive improvement.

Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals.

Neuroligin-1 is a potent trigger for the de novo formation of synaptic connections, and it has recently been suggested that it is required for the maturation of functionally competent excitatory synapses. Despite evidence for the role of neuroligin-1 in specifying excitatory synapses, the underlying molecular mechanisms and physiological consequences that neuroligin-1 may have at mature synapses of normal adult animals remain unknown. By silencing endogenous neuroligin-1 acutely in the amygdala of live behaving animals, we have found that neuroligin-1 is required for the storage of associative fear memory. Subsequent cellular physiological studies showed that suppression of neuroligin-1 reduces NMDA receptor-mediated currents and prevents the expression of long-term potentiation without affecting basal synaptic connectivity at the thalamo-amygdala pathway. These results indicate that persistent expression of neuroligin-1 is required for the maintenance of NMDAR-mediated synaptic transmission, which enables normal development of synaptic plasticity and long-term memory in the amygdala of adult animals.

Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation.

BACKGROUND: Naturally occurring antioxidants were used to regulate the skin damage caused by ultraviolet (UV) radiation because several antioxidants have demonstrated that they can inhibit wrinkle formation through prevention of matrix metalloproteinases (MMPs) and/or increase of collagen synthesis. OBJECTIVE: We examined the effect of oral administration of the antioxidant mixture of vitamin C, vitamin E, pycnogenol, and evening primrose oil on UVB-induced wrinkle formation. In addition, we investigated the possible molecular mechanism of photoprotection against UVB through inhibition of collagen-degrading MMP activity or through enhancement of procollagen synthesis in mouse dorsal skin. METHODS: Female SKH-1 hairless mice were orally administrated the antioxidant mixture (test group) or vehicle (control group) for 10 weeks with UVB irradiation three times a week. The intensity of irradiation was gradually increased from 30 to 180 mJ/cm2. Microtopographic and histological assessment of the dorsal skins was carried out at the end of 10 weeks to evaluate wrinkle formation. Western blot analysis and EMSA were also carried out to investigate the changes in the balance of collagen synthesis and collagen degradation. RESULTS: Our antioxidant mixture significantly reduced UVB-induced wrinkle formation, accompanied by significant reduction of epidermal thickness, and UVB-induced hyperplasia, acanthosis, and hyperkeratosis. This antioxidant mixture significantly prevented the UVB-induced expressions of MMPs, mitogen-activated protein (MAP) kinase, and activation of activator protein (AP)-1 transcriptional factor in addition to enhanced type I procollagen and transforming growth factor-beta2 (TGF-beta2) expression. CONCLUSION: Oral administration of the antioxidant mixture significantly inhibited wrinkle formation caused by chronic UVB irradiation through significant inhibition of UVB-induced MMP activity accompanied by enhancement of collagen synthesis.

Inhibitory effect of procyanidin oligomer from elm cortex on the matrix metalloproteinases and proteases of periodontopathogens.

OBJECTIVES: The purpose of this study was to evaluate a partially purified extract (elm extract) from the Ulmi cortex (Ulmi macrocarpa Hance) and its active ingredient, a mix of procyanidin oligomers (3 to 12 flavan-3-ol monomers, an average molecular weight of 1,518 with an average polymerization degree of 5.3) for a possible inhibitory effect against proteases. BACKGROUND: Host-derived matrix metalloproteinases (MMPs) and bacterial proteases play important roles in the gingival tissue destruction that is a characteristic of periodontitis. The inhibitors of these proteases may be developed into therapeutic agents against periodontitis. METHODS: The inhibitory effects were assessed by gelatin zymography. The MMPs tested were originated from the gingival crevicular fluid (GCF) of adult periodontitis patients and from the conditioned media of cultured periodontal ligament (PDL) cells, which provided the proMMP-2 and activated MMP-2 when treated with a periodontopathogen, Treponema lecithinolyticum. Bacterial enzymes tested were secreted forms from two major periodontopathogens, Porphyromonas gingivalis and Treponema denticola. In addition, the inhibitory effects on trypsin-like enzymes from these two periodontopathogens were assayed by the n-benzoyl-DL-arginine-naphthylamide (BANA) test. RESULTS: The elm extract and the procyanidin oligomer (100-1,000 microg/ml) exhibited potent inhibitory effects on the MMPs in GCF (chiefly MMP-8 and MMP-9), the pro and active forms of MMP-2, and secreted and trypsin-like enzymes from T. denticola and P. gingivalis. CONCLUSIONS: These results suggest that elm cortex should be considered as a potential agent against periodontal diseases, due to its inhibitory action on MMPs and the proteases of periodontopathogens.

Anti-allergic action of buckwheat (Fagopyrum esculentum Moench) grain extract.

The anti-allergic action of buckwheat grain extract (BGE) was investigated using rodent experimental models. The oral, intraperitoneal and intradermal administration of BGE significantly inhibited the compound 48/80-induced vascular permeability documented by Evans blue extravasation. In addition, BGE showed potent inhibitory effect on passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, BGE revealed to possess inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells (RPMC). Moreover, BGE inhibited the IL-4 and TNF-alpha mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Taken together, these results suggest that anti-allergic action of BGE may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.