Oral administration of spa-derived green alga improves insulin resistance in overweight subjects: Mechanistic insights from fructose-fed rats.

Advanced glycation end products (AGEs) and their receptor (RAGE) system evoke inflammatory reactions and insulin resistance in adipocytes. Spa-derived green alga Mucidosphaerium sp. (MS) had anti-inflammatory properties in vitro. We examined here whether and how MS could ameliorate insulin resistance in fructose-rich diet-fed rats, and conducted a randomized, double blind, placebo-controlled trial to investigate the effects of MS on insulin resistance in overweight subjects. Oral administration of MS for 8 weeks significantly decreased random blood glucose, and fasting insulin, oxidative stress levels, and improved homeostasis model assessment of insulin resistance (HOMA-IR) values in fructose-fed rats, which were associated with the reduction of AGEs, RAGE, 8-hydroxy-2'-deoxy-guanosine, NADPH oxidase activity, macrophage and lymphocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, and adipocyte size in the adipose tissues as well as restoration of adiponectin levels. MS decreased the AGE-induced NADPH oxidase activity, ROS generation, MCP-1 and RAGE gene expression, and lipid accumulation in differentiated adipocytes, while it restored the decrease in adiponectin mRNA levels. An anti-oxidant, N-acetylcysteine mimicked the effects of MS on ROS generation, RAGE gene expression, and lipid accumulation. Oral intake of MS for 12 weeks significantly decreased systolic and diastolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, HDL-cholesterol and creatinine in overweight subjects. Baseline-adjusted diastolic blood pressure, fasting plasma glucose, fasting insulin, and HOMA-IR values were significantly lower in MS treatment group than in placebo. Our present findings suggest that MS may improve insulin resistance by blocking the AGE-RAGE-oxidative stress axis in the adipose tissues.

Assistance of human serum albumin to photo-sensitized inactivation of Saccharomyces cerevisiae with axially pyridinio-bonded P-porphyrins.

As singlet-oxygen ((1)O2) sensitizer, water-soluble P-porphyrins (1) were prepared by the modification of axial ligands of tetraphenylporphyrinatophosphorus by N-alkyl-pyridinium group to give bis[3-(1-alkyl-4-pyridinio)propoxo]tetraphenylporphyrinatophosphorus(V) (alkyl=hexyl (1a) and butyl (1b)) and bis[5-(3-alkyl-1-pyridinio)-3-oxapentyloxo] tetraphenylporphyrinatophosphorus(V) (alkyl=hexyl (1c), butyl (1d), and ethyl (1e)). The quantum yields (ΦΔ) for the formation of (1)O2 were extremely high (e.g. ΦΔ=0.88 (1a) and 0.87 (1c)). The 1 could bind human serum albumin (HSA) with high binding constants to produce a complex of HSA with 1 (1/HSA). Here, inactivation of Saccharomyces cerevisiae (yeast) was examined using the complex of HSA (400nM) with 1 (20-50nM) under visible-light irradiation. The bactericidal activity of 1 was evaluated by half-life (T1/2 in min) which was time required to be reduced to one-half initial concentration of yeasts. Under irradiation in the presence of HSA, minimum concentrations ([P]) of 1 were adjusted as T1/2 became the values among 0-120min. The [P] values were determined to be 20nM for 1a, 30nM for 1b, and 50nM for 1c-1e. The 1/HSA sterilized yeast with 12-36min of T1/2 when the concentration of 1 was set to [P]. In the photo-activation in the absence of HSA at the concentration of [P] of 1, however, the T1/2 values of 1a, 1b, 1d, and 1e were >120min and T1/2 of 1c was 44min. Thus, the complexation of 1 with HSA apparently enhanced the bactericidal activity of 1. This is the first finding on the assistance of HSA to the photo-inactivation of yeast cell by porphyrins.