Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials.

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): -0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: -0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.

A putative role for histone deacetylase in the differentiation of human erythroid cells.

Histone acetylation controls the expression of specific genes in eukaryotic cells. We investigated the role of histone deacetylases (HDACs) in the differentiation of human erythroid cells, using pharmacological approaches. When CD36+ erythroid precursor cells, generated from CD34+ cells with stem cell factor, flt-3 ligand, thrombopoietin, interleukin-3, interleukin-6, and erythropoietin, were cultured with an HDAC inhibitor FK228 (depsipeptide) at a specified dose in the presence of erythropoietin, their differentiation was inhibited, as determined by the expression of CD45 and glycophorin A. Addition of the same dose of FK228 to cultures did not affect the growth of CD36+ cells. Regardless of the presence or absence of FK228, cultured CD36+ cells displayed similar proliferation kinetics. Analysis of acetylated histones revealed that FK228 upregulated the acetylation status of histones H3 and H4 in CD36+ cells. The inhibition of CD36+ cell differentiation was restored by removal of FK228 from the culture, indicating that the modification of CD36+ cell differentiation by FK228 is reversible. Furthermore, interference with histone deacetylation by FK228 inhibited the generation of CD36+ erythroid cells from CD34+ hematopoietic progenitor cells. Our results indicate the possible involvement of HDACs in human erythropoiesis, especially the regulation of erythroid cell differentiation.

Suppressive effect of antibiotic siomycin on antibody production.

The antibiotic thiazole compound siomycin, which we have found from the culture broth of Actinomycetes (strain No.806097) in search of antibody production inhibitor, showed the in vitro immunosuppressive property against B-cells stimulated with T-cell independent antigen DNP-LPS (dinitrophenyl-lipopolysaccharide) while it also showed inhibitory effect against T-cell proliferation. Its inhibitory mechanism was considered to be different from that of FK506, the representative of T-cell immunosuppressant. Moreover, siomycin showed inhibitory effect in both T-cell dependent and independent murine antibody production models and decreased the severity in murine collagen arthritis model. Therefore, siomycin is a unique immunosuppressant which has potential for the treatment of some antibody-mediated diseases.

Nilvadipine attenuates mesangial expansion and glomerular hypertrophy in diabetic db/db mice, a model for type 2 diabetes.

BACKGROUND: The renoprotection achieved by angiotensin II blockade in the treatment of diabetic nephropathy is well established in both the clinical and the experimental settings. In contrast, the therapeutic efficacy of calcium channel blockers (CCBs) in the treatment of diabetic nephropathy still remains controversial. METHODS: In the present study, we compared the effects of an angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine CCB, nilvadipine, on nephropathy in the db/db mouse, a rodent model of type 2 diabetes. Male db/db mice were divided into the following three groups at the age of 11 weeks, when treatment was started: vehicle, enalapril (10 mg/kg per day), and nilvadipine (10 mg/kg per day). Blood pressure, urine, and blood chemistry were monitored at the age of 17 and 27 weeks, and kidney samples were obtained at 29 weeks. Morphological changes were analyzed on periodic acid-Schiff-stained sections. Lipid peroxidation in kidney homogenates was measured. RESULTS: Blood pressure remained normal and was similar in the three groups until 27 weeks. Blood glucose exceeded 300 mg/dl throughout the study in all groups. Reduction of microalbuminuria at 27 weeks, compared to the vehicle group, was 37% and 52% in the enalapril- and nilvadipine-treated groups, respectively. Increased lipid peroxidation was suppressed by 15% and 83% in the enalapril- and nilvadipine-treated groups, respectively. Glomerular hypertrophy, assessed by cross-sectional glomerular area, was significantly suppressed in the nilvadipine group, but not in the enalapril group, compared to the vehicle group. CONCLUSIONS: Nilvadipine shows a stronger renoprotective effect than enalapril in the db/db mouse, independent of the blood-pressure-lowering effect. An antioxidative effect, indicated by the reduction in lipid peroxidation, may partly contribute to the renoprotection conferred by nilvadipine.

FR901512, a novel HMG-CoA reductase inhibitor produced by an agonomycetous fungus no. 14919. II. Biological profiles.

FR901512, a new specific inhibitor of HMG-CoA reductase, was isolated from the culture of an agonomycetous fungus No. 14919. FR901512 inhibited cholesterol synthesis from [14C] acetate in Hep G2 cells with an IC50 of 1.0 nM. An increase of cell surface LDL receptors observed on the FR901512 treated human hepatoma cell line Hep G2 cells. Single oral administration of FR901512 strongly inhibited sterol synthesis in rats. Daily oral administration of FR901512 to beagle dogs decreased plasma cholesterol levels.

FR171456, a novel cholesterol synthesis inhibitor produced by Sporormiella minima No. 15604. I. Taxonomy, fermentation, isolation, physico-chemical properties.

FR171456 and FR173945, novel and potent cholesterol synthesis inhibitors, have been isolated from the fermentation broth of a fungal strain No. 15604. This strain was identified Sporormiella minima from its mycological characteristics. FR171456 and FR173945 strongly inhibited cholesterol synthesis in human hepatoma cell line Hep G2. These compounds also have in vitro antifungal activity against Candida albicans and Aspergillus fumigatus.

FR171456, a novel cholesterol synthesis inhibitor produced by Sporormiella minima No. 15604. II. Biological activities.

Novel cholesterol synthesis inhibitors FR171456 and FR173945 were isolated from the culture broth of Sporormiella minima No. 15604. FR171456 strongly inhibited the cholesterol synthesis and up-regulated the LDL-receptor expression in human hepatoma cell line Hep G2. Single oral administration of FR171456 inhibited in vivo hepatic sterol synthesis in rats. And FR171456 shows a significant serum cholesterol-lowering effect in a cholesterol fed rabbit model.

FR901512, a novel HMG-CoA reductase inhibitor produced by an agonomycetous fungus No. 14919. II. Taxonomy of the producing organism, fermentation, isolation and physico-chemical properties.

Novel compounds FR901512 and FR901516 were isolated from the fermentation broth of agonomycete strain No. 14919. FR901512 and FR901516 possess unique tetralin ring in their structure. These compounds were potent inhibitors of the cholesterol synthesis in human hepatoma cell line Hep G2. FR901512 shows strong 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity with an IC50 value of 0.95 nM.

FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities of FR252921, FR252922 and FR256523.

Novel immunosuppressive agents, FR252921, FR252922 and FR256523 were isolated from the cultured broth of a bacterial strain No. 408813. The strain was identified Pseudomonas fluorescens from morphological and physiological characteristics. FR252921, FR252922 and FR256523, novel compounds containing macrolactone ring, showed immunosuppressive activity against murine splenocyte proliferation stimulated with lipopolysaccharide (LPS) or anti-CD3 mAb in vitro.

FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action.

A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibited splenic proliferation stimulated with LPS, insensitive to calcinuerin inhibitor. In this study, FR252921 was found to inhibit IL-2 and IL-12 production as well as proliferaion of splenocyte. Analysis of transcription activity revealed that FR252921 inhibited activating protein-1 (AP-1). Exposures of antigen presenting cells (APC) to FR252921 attenuated proliferation supplemented by naïve T cells. Further, FR252921 strongly suppressed splenic dendritic cell proliferation stimulated with LPS and anti-CD40 mAb, while it did not inhibit purified T cell activation, including CD154 expression and IL-2 production. These results suggest that APC is dominant target cell population.

FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 III. In vivo activities.

A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibit activating protein-1 (AP-1) transcription activity and act dominantly against antigen presenting cells comparing to T cell. Possibility of FR252921 as concomitant drug of FK506, T-cell specific inhibitor was evaluated. FR252921 showed synergy with FK506 in immunosuppressive activity both in splenic proliferation and in murine skin transplantation.