ABSTRACT
Guaiac resin, extracted from the heartwood of Guaiacum officinale L. or G. sanctum L., is speculated to have anti-inflammatory effects. Lignans were purified from guaiac resin (also known as gum guaiacum) by monitoring the nitric oxide (NO) production in rat hepatocytes treated with an inflammatory cytokine interleukin-1ß (IL-1ß). Six lignans were purified from guaiac resin and identified as: dehydroguaiaretic acid (1), (+)-trans-1,2-dihydrodehydroguaiaretic acid (2), furoguaiaoxidin (3), meso-dihydroguaiaretic acid (4), furoguaiacin (i.e., α-guaiaconic acid) (5), and nectandrin B (6). To our knowledge, this is the first time that 1 has been isolated from guaiac resin as a non-derivative. Compounds 2 and 6 were first found in guaiac resin. Compound 3 was first isolated from a natural source as a non-derivative. Furthermore, 1-6 significantly suppressed NO production in IL-1ß-treated hepatocytes. Because anti-inflammatory compounds suppress NO production, this system is often used to measure the anti-inflammatory effects of Kampo drugs and herbal constituents. The NO-suppressing activity of the six lignans isolated in this study indicates that guaiac resin has anti-inflammatory effects and that these lignans may be responsible for the anti-inflammatory effects of guaiac resin.
Subject(s)
Guaiac/chemistry , Hepatocytes/drug effects , Interleukin-1beta/metabolism , Lignans/therapeutic use , Nitric Oxide/metabolism , Resins, Plant/chemistry , Animals , Lignans/pharmacology , Male , Nitric Oxide/biosynthesis , RatsABSTRACT
Although phosphatidylinositol (PI) is an important component in all plants and animals, there is no toxicity report when purified PI is orally administrated to animals. As a safety evaluation of PI, acute, subchronic and genotoxicity studies were conducted with purified PI from soy lecithin (Asahi Kasei PI). Up to 2,000 mg/kg of Asahi Kasei PI was administrated once orally to male and female rats. There were no deaths or any clinical sign in any group throughout the observation period. Then, Asahi Kasei PI was repeatedly administered orally to male and female rats at daily doses of 100, 300 and 1,000 mg/kg for 13 weeks. Neither death nor any toxicological signs during the administration period and no changes related to the test substance administered were observed in any group with regard to body weight, food consumption, ophthalmoscopy, hematology, blood biochemistry, necropsy, organ weights or histopathology. Based on these results, the no-observed-adverse effect level (NOAEL) of Asahi Kasei PI was considered to be 1,000 mg/kg/day for male and female rats. Genotoxicity evaluation of Asahi Kasei PI was also carried out by the bacterial reverse mutation test (Ames test) and in vitro chromosome aberration test in compliance with the Japanese guidelines on genotoxicity testing of pharmaceuticals, the OECD guidelines for testing chemicals and guidelines for designation of food additives and for revision of standards for use of food additives. The results indicate neither increases of revertant colonies nor chromosome aberration, suggesting that Asahi Kasei PI has high safety in genotoxicity.
Subject(s)
Glycine max/chemistry , Lecithins/chemistry , Mutagens/toxicity , Phosphatidylinositols/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Cells, Cultured , Chromosome Aberrations , Clinical Chemistry Tests , Cricetinae , Cricetulus , Eating/drug effects , Female , Hematologic Tests , Male , Mutagens/classification , No-Observed-Adverse-Effect Level , Phosphatidylinositols/classification , Plant Extracts/toxicity , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Salmonella typhimurium/geneticsABSTRACT
Recent studies have shown that dietary phospholipids, especially phosphatidylcholine and phosphatidylserine, have various beneficial biological effects. However, there are not enough data concerning the physiological function of dietary phosphatidylinositol (PI). The metabolic syndrome, a cluster of metabolic abnormalities such as dyslipidemia, diabetes mellitus, and hypertension, is widespread and increasingly prevalent diseases in industrialized countries. In the present study, we evaluated that the effect of dietary PI on cholesterol metabolism in metabolic syndrome model Zucker (fa/fa) rats. For 4 weeks, rats were fed semisynthetic diets containing either 7% soybean oil or 5% soybean oil plus 2% PI. Dietary PI prevented the mild hypercholesterolemia and hepatic cholesterol accumulation in Zucker (fa/fa) rats. These effects were attributable to an increased fecal bile acid excretion and to the tendencies of decreased ACAT1 mRNA level and increased CYP7A1 mRNA level in the liver. Additionally, dietary PI markedly increased microsomal PI content in the liver of Zucker (fa/fa) rats. Our study suggests that dietary PI normalizes cholesterol metabolism through the enhancement of fecal bile acid excretion in the metabolic syndrome model rats.
