The Beneficial Effects of Regular Intake of Lactobacillus paragasseri OLL2716 on Gastric Discomfort in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

We investigated the effects of Lactobacillus paragasseri OLL2716 on gastrointestinal symptoms in healthy adults with gastric complaints. In this randomized, double-blind, placebo-controlled trial, 174 healthy Japanese adults were randomly assigned to an OLL2716 or placebo group, and each group consumed 85 g of yogurt containing L. paragasseri OLL2716 or placebo yogurt daily for 12 weeks. The primary endpoint was the change in gastric symptoms from baseline as per the participants' questionnaires at 6 and 12 weeks. The secondary endpoints were changes from baseline in the short-form Nepean Dyspepsia Index (SF-NDI), the Gastrointestinal Symptom Rating Scale (GSRS), and the Council on Nutrition Appetite Questionnaire-Japanese (CNAQ-J) scores at 6 and 12 weeks. The primary endpoint data showed that the changes in "epigastric pain" at 6 and 12 weeks were significantly decreased in the OLL2716 group compared with those in the placebo group. Additionally, the changes in "epigastric pain syndrome-like symptoms" were significantly decreased in the OLL2716 group compared with those in the placebo group at 6 weeks. The SF-NDI items that improved at 6 weeks were "irritable, tense, or frustrated", "enjoyment of eating or drinking", and "tension", which are sub-scales related to mental stress. The items "Over-all" in the GSRS and "feeling hungry" in the CNAQ-J significantly improved in the OLL2716 group compared with the placebo group at 12 weeks. The results suggest that regular intake of L. paragasseri OLL2716 may improve both gastric discomfort and mental stress in healthy adults with gastric complaints, such as postprandial fullness or early satiety.

Lactobacillus gasseri PA-3 reduces serum uric acid levels in patients with marginal hyperuricemia.

Several studies have reported that Lactobacillus gasseri PA-3 reduces the level of serum uric acid (SUA) in patients with hyperuricemia. However, it remains unknown how PA-3 affects uric acid metabolism. In the present study, we examined effects of PA-3-containing yoghurt on uric acid metabolism in patients with marginal hyperuricemia. Sixteen patients with SUA > 357 µmol/L (marginal hyperuricemia) were enrolled. PA-3-containing yoghurt was administered for 8 weeks. Uric acid metabolism was evaluated just before and 8 weeks after the administration and at 4 weeks after the administration ended (post-administration). SUA levels after the administration were significantly lower than that before the administration and remained low at post-administration. Urinary uric acid concentration (Uur) after the administration were significantly lower than that before the administration. However, post-administration Uur levels were comparable to those before the administration. Therefore, PA-3-containing yoghurt significantly reduced the levels of SUA and Uur in patients with marginal hyperuricemia.

Lactobacillus gasseri PA-3 Uses the Purines IMP, Inosine and Hypoxanthine and Reduces their Absorption in Rats.

Excessive intake of purine-rich foods elevates serum levels of uric acid. Animal and fish meats contain high amounts of inosine and its related purines, and the reduction of taking those purines is crucial for the improvement of serum uric acid levels. We previously showed that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine and its related purines and that oral treatment with PA-3 reduced adenosine absorption in rats. This study investigated whether PA-3 also incorporates IMP (inosine 5'-monophosphate), inosine, and hypoxanthine, and whether it reduces their absorption in rats. PA-3 was incubated in vitro with radioisotope (RI)-labeled IMP, inosine, and hypoxanthine, and the incorporation of these compounds by PA-3 was evaluated. In addition, rats were orally administered PA-3 along with RI-labeled inosine 5'-monophosphate, inosine, or hypoxanthine, and the ability of PA-3 to attenuate the absorption of these purines was determined. PA-3 incorporated all three purines and displayed greater proliferation in the presence than in the absence of these purines. Oral administration of PA-3 to rats reduced the absorption of IMP, inosine, and hypoxanthine. These results indicate that PA-3 reduces the absorption of purines contained in foods and it is expected that PA-3 contributes attenuation of the excessive intake of dietary purines.

Amide-type adduct of dopamine - plausible cause of Parkinson diseases.

Dopamine is the endogenous neurotransmitter produced by nigral neurons. Dopamine loss can trigger not only prominent secondary morphological changes, but also changes in the density and sensitivity of dopamine receptors; therefore, it is a sign of PD development. The reasons for dopamine loss are attributed to dopamine's molecular instability due to it is a member of catecholamine family, whose catechol structure contributes to high oxidative stress through enzymatic and non-enzymatic oxidation. Oxidative stress in the brain easily leads to the lipid peroxidation reaction due to a high concentration of polyunsaturated fatty acids (PUFA), such as docosahexaenoic acid (DHA, C22:6/ω-3) and arachidonic acid (AA, C18:4/ω-6). Recent studies have shown that lipid hydroperoxides, the primary peroxidative products, could non-specifically react with primary amino groups to form N-acyl-type (amide-linkage) adducts. Therefore, based on the NH2-teminals in dopamine's structure, the aims of this chapter are to describes the possibility that reactive LOOH species derived from DHA/AA lipid peroxidation may modify dopamine to form amide-linkage dopamine adducts, which might be related to etiology of Parkinson's diseases.

Effect of sesame lignans on TNF-alpha-induced expression of adhesion molecules in endothelial cells.

The expression of cell adhesion molecules (CAMs) has been implicated as one of the most important causes of the development of inflammatory diseases such as atherosclerosis, and, it is speculated that the prevention of it is an effective approach to the control of atherosclerosis. In the present study, we investigated the effect of sesame lignans on the expression of CAMs in human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha). Based on cell-ELISA analysis, we found that sesaminol-6-catechol downregulated the TNF-alpha-induced expression of CAMs in a dose-dependent manner. Moreover, these inhibitory effects were caused to be drastically exerted by downregulating the CAM proteins in TNF-alpha-activated HUVECs at transcriptional level. This suggests, that sesaminol-6-catehcol suppresses the expression of CAMs, and may be an active component of sesame lignans.

Assessing the neuroprotective effect of antioxidant food factors by application of lipid-derived dopamine modification adducts.

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification and drugs. However, the biomarker by which the effect of the agent on neurodegeneration is determined is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter, and its deficiency is a characterized feature in Parkinson's disease (PD); thus, HED provides a new insight into the understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Assessing the neuroprotective effect of antioxidative food factors by application of lipid-derived dopamine modification adducts.

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification, and drugs. However, the biomarker by which to determine the effect of the agent on neurodegeneration is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter and its deficiency is a characterized feature in Parkinson's disease (PD), thereby HED represents a new addition to understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system using for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Formation of dopamine adducts derived from brain polyunsaturated fatty acids: mechanism for Parkinson disease.

Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson disease. In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (C22:6/omega-3) and arachidonic acid (C18:4/omega-6), which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells, whereas the other adducts were only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the docosahexaenoic acid- and arachidonic acid-derived dopamine adducts in vitro and in vivo, and HED, the arachidonic acid-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson disease.