Promotive effect of Shoyu polysaccharides from soy sauce on iron absorption in animals and humans.

Soy sauce (Shoyu) is a traditional fermented seasoning of Japan and is available throughout the world. We investigated the effect of Shoyu polysaccharides (SPS) prepared from soy sauce on iron absorption in vitro and in vivo. First, by measuring the iron-binding capacity of SPS, it was found that SPS stabilized the solubility of ferrous iron at neutral pH's by forming a complex, Fe-SPS. Second, in experiments with animals, it was found that SPS enhanced the absorption and/or pooling of iron in organs when anemic rats were fed iron-supplemented diets. Third, in a 4-week randomized, double-blind, placebo-controlled parallel group study, healthy women were treated with 600 mg of SPS (n = 22) or placebo (n = 23) each day. After the 4 weeks, serum levels of iron, hematocrit, and hemoglobin were significantly higher (P < 0.05) in the SPS-treated than in the placebo-treated group. In conclusion, SPS of soy sauce enhanced iron absorption, and soy sauce is a potentially promising seasoning for the treatment of anemia through food.

In vitro and in vivo anti-allergic activity of soy sauce.

Soy sauce (Shoyu) is a traditional fermented seasoning of Japan and available throughout the world. Polysaccharides were obtained from dialysate of Shoyu, and these Shoyu polysaccharides (SPS) were examined for anti-allergic activity in vitro and in vivo. The SPS originated from partially-degraded polysaccharides of soybeans by mold enzymatic hydrolyses, and Shoyu contained about 1% (w/v) SPS. First, the inhibitory effects of SPS on hyaluronidase, which is known to be related to inflammation and allergic responses, were as potent as those of an anti-allergic medicine, disodium cromoglycate. Second, SPS significantly inhibited the release of histamine from rat basophilic leukemia (RBL-2H3) cells, which had been induced by the antigen. Third, orally administered SPS had a significant suppressive effect on passive cutaneous anaphylaxis induced in the ears of mice. These results suggest that SPS may have anti-allergic activities, and soy sauce is a potentially promising seasoning for the treatment of allergic diseases through food.

Quality of life improvement with soy sauce ingredients, Shoyu polysaccharides, in perennial allergic rhinitis: a double-blind placebo-controlled clinical study.

Soy sauce (Shoyu) is a traditional fermented seasoning of East Asian countries and available throughout the world. We obtained polysaccharides from raw soy sauce, and showed the anti-allergic activities of these Shoyu polysaccharides (SPS) in vitro and in vivo. The present study determined whether oral supplementation of SPS is an effective intervention for patients with perennial allergic rhinitis. In a 4-week randomized, double-blind, placebo-controlled parallel group study, patients with mild perennial allergic rhinitis were treated with 600 mg of SPS (n=11) or placebo (n=10) each day. After 4 weeks of treatment with SPS, a reduction in symptom scores for runny nose, sore throat, and itchy eyes were significantly changed from the baseline within the group (p<0.05), but no change in these scores was observed over 4 weeks of treatment in the placebo group. However, differences in the symptom scores during the study period were not significantly different between the groups. The total symptom score, calculated from the sum of individual scores, showed a significant difference between the 2 groups after 4 weeks of treatment (p<0.05). The efficacy of global symptoms score, which was defined as the adjusted mean change from baseline during 4 weeks of treatment, also showed a significant improvement in the SPS group (p<0.05). An overall evaluation of the medication's effectiveness after 4 weeks treatment showed significant differences between the SPS- and placebo-treated groups (p<0.05). In conclusion, SPS of soy sauce improved the quality of life for patients with perennial allergic rhinitis, and soy sauce would be useful in an anti-allergic therapy utilizing everyday foods.

Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPARgamma-independent mechanism.

We have previously reported that troglitazone inhibits proinflammatory cytokine production in chronic pancreatitis. In the present study, we show that troglitazone prevents the progression of chronic pancreatitis by inhibiting the proliferation of pancreatic stellate cells (PSCs) via a PPARgamma-independent mechanism. WBN/Kob rats with spontaneous chronic pancreatitis were fed troglitazone-containing rat chow for 3 or 6 months. Pancreatic fibrosis and expression of alpha-SMA were markedly attenuated by troglitazone. Rat PSCs expressed a higher level of PPARgamma1 mRNA than of PPARgamma2 mRNA. PSCs were transiently cotransfected with a dominant negative mutant PPARgamma1 and a PPAR-driven reporter gene. Troglitazone increased reporter activity and the mutant receptor abrogated wild-type receptor activity in a dose-dependent manner. Troglitazone inhibited cell proliferation by blocking cell-cycle progression beyond the G1 phase. These effects were observed in mutant receptor-transfected cells as well as cells transfected with the control vector. The effect of troglitazone on alpha1(I) procollagen mRNA and MCP-1 mRNA was unaffected by inhibition of endogenous PPARgamma1 receptor activity. These results suggest that troglitazone may serve as novel therapeutic agent for the treatment of chronic pancreatitis. The antifibrotic effect of troglitazone appears to be mediated, in part, via a PPARgamma-independent mechanism.

Protein-bound 4-hydroxy-2-hexenal as a marker of oxidized n-3 polyunsaturated fatty acids.

In the present study, to investigate the contribution of n-3 PUFAs in the oxidative modification of protein in vivo, we characterize the covalent binding of 4-hydroxy-2-hexenal (HHE), a potent cytotoxic aldehyde originating from the peroxidation of n-3 PUFAs, to protein and describe the production of this aldehyde in oxidatively modified LDL and in human atherosclerotic lesions. Upon incubation with BSA, HHE was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a potential marker of oxidatively modified proteins under oxidative stress. To detect the protein-bound HHE in vivo, we raised monoclonal antibody HHE53 (MAb HHE53) directed to the HHE-modified protein and identified the Michael addition-type HHE-histidine adduct as the major epitope. This antibody reacted with copper-oxidized LDL, suggesting that HHE was produced during the oxidative modification of LDL. In addition, we demonstrated that the materials immunoreactive to MAb HHE53 indeed constituted the atherosclerotic lesions, in which intense positivity was associated primarily with macrophage-derived foam cells. The results of this study suggest that the reaction between oxidized n-3 PUFAs and protein might represent a process common to the formation of degenerative proteins during aging and its related diseases.

Oxidative stress in the human fetal brain: an immunohistochemical study.

Because accumulation of oxidative modification products seems to relate to aging and has not been fully studied in fetal brains, an immunohistochemical examination was performed on nine brains ranging from 22-40 weeks of gestation. These brains did not demonstrate lesions except hypoxic-ischemic changes. Advanced glycation end products and 4-hydroxynonenal are generally reported to be negative in neurons of normal young brains, but, in the present study, distinct positive immunoreaction was observed in neurons of fetal brains. Positive immunoreaction appeared earlier in the medulla oblongata than in the cerebrum, and 4-hydroxynonenal began to accumulate earlier than advanced glycation end products. As for glial cells, advanced glycation end products and 4-hydroxynonenal were positive in reactive astrocytes in mid- to late gestation. Because hypoxic-ischemic changes were observed in most of the patients, it is possible that oxidative stress caused by hypoxic-ischemic may be involved in the accumulation of these products in the fetal brain. 8-Hydroxy-2'-deoxyguanosine was negative even in patients demonstrating positive reaction for advanced glycation end products and 4-hydroxynonenal. In the fetal brain, DNA might be strongly protected from oxidative damage. 4-Hydroxynonenal is generally positive in the cytoplasm but was positive in the nucleus of immature neurons and glial cells in the present study, suggesting a unique metabolism of the fetal brain.