Dried and Fermented Powders of Edible Algae (Neopyropia yezoensis) Attenuate Hepatic Steatosis in Obese Mice.

Edible algae Neopyropia yezoensis is used as "Nori", its dried sheet product, in Japanese cuisine. Its lipid components reportedly improve hepatic steatosis in obese db/db mice. In this study, we prepared "Nori powder (NP)" and "fermented Nori powder (FNP)" to utilize the functional lipids contained in "Nori" and examined their nutraceutical effects in vivo. Male db/db mice were fed a basal AIN-76 diet, a 10% NP-supplemented diet, or a 10% FNP-supplemented diet for 4 weeks. We detected eicosapentaenoic acid (EPA) present in both NP and FNP in the serum and liver of db/db mice in a dose-dependent manner. The NP diet reduced hepatic triglyceride accumulation (by 58%) in db/db mice by modulating gene expression, which resulted in the inhibition of lipogenic enzyme activity. Additionally, NP intake significantly suppressed the expression of inflammatory genes in the liver and hepatic injury marker levels in the sera (by 26%) of db/db mice. The FNP diet also led to a marked reduction in hepatic triglyceride accumulation (by 50%) and hepatic injury (by 28%) in db/db mice, and the mechanism of these alleviative actions was similar to that of the NP diet. Although the EPA content of FNP was one-third that of NP, metabolomic analysis revealed that bioactive betaine analogs, such as stachydrine, betaine, and carnitine, were detected only in FNP. In conclusion, we suggest that (1) mechanical processing of "Nori" makes its lipid components readily absorbable by the body to exert their lipid-lowering effects, and (2) fermentation of "Nori" produces anti-inflammatory molecules and lipid-lowering molecules, which together with the lipid components, can exert hepatic steatosis-alleviating effects.

Genomic Epidemiology and Evolution of Scallion Mosaic Potyvirus From Asymptomatic Wild Japanese Garlic.

Scallion mosaic virus (ScaMV) belongs to the turnip mosaic virus phylogenetic group of potyvirus and is known to infect domestic scallion plants (Allium chinense) in China and wild Japanese garlic (Allium macrostemon Bunge) in Japan. Wild Japanese garlic plants showing asymptomatic leaves were collected from different sites in Japan during 2012-2015. We found that 73 wild Japanese garlic plants out of 277 collected plants were infected with ScaMV, identified by partial genomic nucleotide sequences of the amplified RT-PCR products using potyvirus-specific primer pairs. Sixty-three ScaMV isolates were then chosen, and those full genomic sequences were determined. We carried out evolutionary analyses of the complete polyprotein-coding sequences and four non-recombinogenic regions of partial genomic sequences. We found that 80% of ScaMV samples have recombination-like genome structure and identified 12 recombination-type patterns in the genomes of the Japanese ScaMV isolates. Furthermore, we found two non-recombinant-type patterns in the Japanese population. Because the wild plants and weeds may often serve as reservoirs of viruses, it is important to study providing the exploratory investigation before emergence in the domestic plants. This is possibly the first epidemiological and evolutionary study of a virus from asymptomatic wild plants.

Anti-stress effects of rosemary (Rosmarinus officinalis L.) leaf extract on intestinal goblet cells and immobility of forced-swimming test in BALB/c mice.

We investigated the anti-stress effect of rosemary (Rosmarinus officinalis L.) leaf extract (RLE) on restraint-stressed mice and found that RLE alleviated decreases in the number of intestinal goblet cells and amount of hepatic triglycerides. It also decreased the immobility time in the forced-swimming test and activation of microglia in the brain, suggesting that RLE has beneficial effects on stress-induced dysfunctions.

Soy Protein Isolate Suppresses Lipodystrophy-induced Hepatic Lipid Accumulation in Model Mice.

Lipodystrophies are acquired and genetic disorders characterized by the complete or partial absence of body fat with a line of metabolic disorders, including hepatic steatosis. Because soy protein isolate (SPI) has been reported to reduce cholesterol and triglyceride levels in animals and humans, we explored the effect of SPI on the pathophysiology of hepatic lipid accumutaion in a diet-induced lipodystrophy model mice. Four weeks of the lipodystrophy model diet induced hepatic lipid accumulation concomitant with marked deficiencies of adipose tissue and serum adipocytokines in mice. However, supplementing the lipodystrophy model diet with SPI could alleviate the hepatic lipid acculation without affecting the lipoatrophic effect of the diet. Enhanced lipogenesis is the principal mechanism of hepatic steatosis in this model, but SPI supplementation significantly attenuated the increase in enzyme activity and/or mRNA expression. Additionally, SPI supplementation upregulated the hepatic mRNA expression of an enzyme involved in cholesterol catabolism. In conclusion, our results indicate the possibility of dietary SPI to attenuate lipodystorophy-induced hepatic steatosis through the direct reduction of hepatic lipogenesis without affecting adipocytokine production.

Carnosic acid protects starvation-induced SH-SY5Y cell death through Erk1/2 and Akt pathways, autophagy, and FoxO3a.

Carnosic acid (CA) is recognized as a unique neuroprotective compound in the herb rosemary, since it induces expression of antioxidant enzymes including heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), and glutathione S-transferase (GST) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a nuclear transcription factor. In this study, we examined the cytoprotective effects of CA against starvation. We found that CA protected starvation-induced SH-SY5Y cell death by activating Akt and extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, CA induced moderate autophagy and dephosphorylation of a transcriptional factor, the forkhead box protein O3a (FoxO3a). These effects of CA play an important role in cytoprotection.

Cecal succinate elevated by some dietary polyphenols may inhibit colon cancer cell proliferation and angiogenesis.

This study demonstrated that 0.5% dietary rutin, ellagic acid, or curcumin markedly increased cecal succinate levels in rats fed a high-fat diet, whereas catechin, caffeic acid, and quercetin did not. Other organic acids were modestly or hardly affected by polyphenols. To clarify the effects of succinate levels increased by polyphenols, this study examined the effects of succinate on the growth and proliferation of colon cancer cells and angiogenesis. The growth and proliferation of HT29 human colon cancer cells and angiogenesis in an ex vivo model were significantly inhibited by succinate at a dose close to that in the cecum of rats fed polyphenols. Furthermore, succinate inhibited the migration of human umbilical vein endothelial cells. These findings suggest that the consumption of some polyphenols affects the health and diseases of the large intestine by elevating succinate.

Antiangiogenic effect of carnosic acid and carnosol, neuroprotective compounds in rosemary leaves.

Carnosic acid, a diterpene in rosemary, is considered to be beneficial in the prevention of chronic neurodegenerative diseases. Recently, it has been found that drugs with antiangiogenic activity lower the risk of neurodegenerative diseases. Thus it is of interest whether carnosic acid has antiangiogenic activity. In this study, carnosic acid suppressed microvessel outgrowth on ex vivo angiogenesis assay using a rat aortic ring at higher than 10 µM. The antiangiogenic effect of carnosic acid was found in angiogenesis models using human umbilical vein endothelial cells with regard to tube formation on reconstituted basement membrane, chemotaxis and proliferation. Although the carnosol in rosemary also suppressed angiogenesis, its effect was not more potent than that of carnosic acid in the ex vivo model. These results suggest that carnosic acid and rosemary extract can be useful in the prevention of disorders due to angiogenesis, and that their antiangiogenic effect can contribute to a neuroprotective effect.

Consumption of vitamin B6 reduces colonic damage and protein expression of HSP70 and HO-1, the anti-tumor targets, in rats exposed to 1,2-dimethylhydrazine.

Mounting evidence indicates that vitamin B6 is a protective factor for colon cancer. Elevations in colonic damage, cell proliferation and heat shock proteins (HSPs, molecular chaperones) have been suggested to be associated with colon carcinogenesis. This study was performed to examine the effect of dietary levels of vitamin B6 (1, 7 or 35 mg pyridoxine HCl/kg diet) for 22 weeks on colon damage, epithelial cell proliferation and expression of HSPs in rats exposed to 1,2-dimethylhydrazine (DMH). Supplemental vitamin B6 with a low vitamin B6 diet (1 mg pyridoxine HCl/kg diet) significantly reduced fecal activity of intestinal alkaline phosphatase (an index of intestinal damage) and the colonic epithelium PCNA labeling index (a marker of cell proliferation). Analysis using ELISA indicated that supplemental vitamin B6 significantly lowered protein levels of colonic HSP70 and heme oxygenase-1, HSP32 (HO-1). However, real-time RT-PCR analysis revealed that the mRNA levels of these HSPs were not decreased by supplemental vitamin B6, suggesting that the lowering effect of vitamin B6 on the colon protein expression of the HSPs is mediated by mechanisms not involving altered gene expression. This study provided evidence that dietary supplemental vitamin B6 suppresses colon damage, epithelial cell proliferation and protein expression of HSP70 and HO-1, the targets for anti-tumor agents, in rats exposed to DMH.

Synthesis and biological evaluation of vitamin K derivatives as angiogenesis inhibitor.

Ten vitamin K(3) derivatives were synthesized and screened for anti-angiogenic activity. Results indicated that amine derivatives (1a-d) exerted a stronger inhibition effect on angiogenesis compared to alkyl derivatives (2a-d). In addition to being the most potent inhibitor, 1b also suppressed human umbilical vein endothelial cell tube formation and proliferation. These results suggest that vitamin K(3) amine derivatives with shorter alkyl chains, such as 1b, could be useful for developing anti-angiogenic agents.

1,4-Naphthoquinone is a potent inhibitor of human cancer cell growth and angiogenesis.

Angiogenesis inhibitors are beneficial for the prevention and treatment of angiogenesis-dependent diseases including cancer. Vitamin K2 and K3, which are naphthoquinone derivatives, inhibit angiogenesis. We examined the anti-cancer and anti-angiogenic effects of naphthoquinones and its structurally related compounds. Among these 13 compounds, 1,4-naphthoquinone strongly inhibited both human colon cancer cell (HCT116) growth and angiogenesis. To clarify the anti-angiogenic mechanism, the effects of 1,4-naphthoquinone on human umbilical vein endothelial cell (HUVEC) tube formation, proliferation and chemotaxis were examined. Consequently, 1,4-naphthoquinone inhibited HUVEC functions. These results suggest that 1,4-naphthoquinone may be useful to cancer therapy.

Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis.

Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase gamma, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.

Dietary lectin lowers serum cholesterol and raises fecal neutral sterols in cholesterol-fed rats.

This study examined the influence of a low level of dietary lectin (0.34%), at a dose that did not affect body weight or food intake, on the concentration of serum cholesterol and fecal excretion of neutral sterols in rats fed a diet containing 0.50% cholesterol and 0.13% sodium cholate for 12 d. In experiment 1, rats fed a diet with 0.34% lectin, concanavalin A, had significantly lower concentrations of serum total cholesterol and hepatic cholesterol, a higher ratio of HDL-cholesterol to total cholesterol, enhanced excretion of fecal neutral sterols and reduced apparent cholesterol absorption or digestibility as compared with rats fed a diet without lectin. Fecal excretion of acidic sterols was unaffected by dietary lectin. In contrast, dietary 0.34% lectin had no significant effect on concentrations of serum total protein or glucose. In experiment 2, we examined whether the cholesterol-lowering activity of the lectin was responsibility for its carbohydrate-binding activity. The effect of dietary lectin on concentrations of serum and hepatic cholesterol and excretion of fecal neutral sterols was prevented by simultaneous administration of methyl-alpha-D-mannopyranoside with specific affinity for the carbohydrate-binding sites of the lectin. These results suggest that dietary lectins might reduce concentrations of serum and hepatic cholesterol by a mechanism involving higher excretion of neutral sterols and that these alterations might be associated with the carbohydrate-binding activity of lectin.

Oxalic acid is available as a natural antioxidant in some systems.

Oxalic acid is found in a wide variety of plants. This study showed that oxalic acid suppressed in vitro lipid peroxidation in a concentration-dependent manner. Furthermore, oxalic acid reduced the rate of ascorbic acid oxidation in the presence of hydrogen peroxide and Cu(2+). These results suggest that oxalic acid is available as a natural antioxidant.