Gene expression profiling of sesaminol triglucoside and its tetrahydrofuranoid metabolites in primary rat hepatocytes.

Sesaminol triglucoside is a major lignin in sesame meal and has a methylenedioxyphenyl group and multiple functions in vivo. As a tetrahydrofurofuran type lignan, sesaminol triglucoside is metabolized to mammalian lignans. This investigation studies the effect of sesaminol triglucoside and its tetrahydrofuranoid metabolites (sesaminol, 2-episesaminol, hydroxymethyl sesaminol-tetrahydrofuran, enterolactone, and enterodiol) on gene expression in primary rat hepatocytes using a DNA microarray. Sesame lignans significantly affected the expression of xenobiotic-induced transcripts of cytochrome P450, solute carrier (SLC), and ATP-binding cassette (ABC) transporters. Changes in gene expression were generally greater in response to metabolites with methylenedioxyphenyl moieties (sesaminol triglucoside, sesaminol, and 2-episesaminol) than to the tetrahydrofuranoid metabolites (hydroxymethyl sesaminol-tetrahydrofuran, enterolactone, and enterodiol). Tetrahydrofuran lignans, such as sesaminol triglucoside, sesamin, hydroxymethyl sesaminol-tetrahydrofuran, and sesaminol changed the expression of ABC transporters.

Tissue distribution and elimination of estrogenic and anti-inflammatory catechol metabolites from sesaminol triglucoside in rats.

Sesaminol triglucoside (STG) is the main sesame (Sesamum indicum L.) lignan. Like many other plant lignans, STG can be converted to the mammalian lignans by intestinal microbiota. The objectives of the present study were to investigate the distribution of STG metabolite in rats, and the effects of STG and its metabolite on in vitro inflammation and estrogenic activities. STG was metabolized via intestinal microflora to a biologically active catechol moiety which would then be absorbed into the body in rats. After oral administration of STG to Sprague-Dawley rats, the concentrations of major STG metabolites in rectum, cecum, colon, and small intestines are higher than those in liver, lung, kidney, and heart. Its concentration in brain is low but detectable. The present study demonstrates that STG may be metabolized to form the catechol metabolites first by intestinal microflora and then incorporated via intestine absorption into the cardiovascular system and transported to other tissues. Results showed that the catechol metabolites were found to be able to penetrate the tail end of intestines (large intestine) and go through urinary excretion. STG metabolites significantly reduced the production of IL-6 and TNF-alpha in RAW264.7 murine macrophages stimulated with lipopolysaccharide. The estrogenic activities of STG metabolites were also established by ligand-dependent transcriptional activation through estrogen receptors. This study clearly shows that STG has anti-inflammatory and estrogenic activities via metabolism of intestinal microflora.

Differential tissue distribution of sesaminol triglucoside and its metabolites in rats fed with lignan glycosides from sesame meal with or without nano/submicrosizing.

Lignan glycosides are important functional compounds in sesame meal. In the present study, we investigated whether the tissue distribution of nano/submicrosized lignan glycosides from sesame meal (N-LGSM) differs from lignan glycosides from sesame meal (LGSM). LGSM was nano/submicrosized with 0.3 mm zirconia beads as the milling media. The average particle size of the 4% LGSM aqueous suspension reduced rapidly from approximately 2 microm to 200 nm after media milling at an agitation speed of 3600 rpm for 30 min. We examined the tissue distribution of sesaminol triglucoside (ST), the main component in LGSM, in Sprague-Dawley (SD) rats. The concentrations of ST were determined in various tissues and plasma within a 24 h period after oral administration of N-LGSM and LGSM (800 mg/kg of body weight). The results showed that higher concentrations of ST and its metabolites (sesaminol, sesaminol sulfate, and sesaminol glucuronide) were found in N-LGSM compared to those in LGSM in most tissues, especially liver and small intestine. Sesaminol glucuronide was the main metabolite in rats. After 3 h of oral administration, around 70% higher concentration of sesaminol glucuronide was found in N-LGSM compared to that in LGSM. This study clearly showed that LGSM is more bioavailable after nano/submicrosizing.

Elimination and metabolism of sesamol, a bioactive compound in sesame oil, in rats.

Sesamol, generally regarded as a main antioxidative component in sesame oil, is generated from sesamolin upon roasting of sesame seed or during bleaching process of sesame oil. This investigation studied the bioavailability and excretion of sesamol in Sprague-Dawley rats. After oral administration of sesamol (p.o. 100 mg/kg) to SD rats, the changes in concentration of sesamol were determined in various excreta within 24 h period. Our results showed that sesamol conjugated metabolites were rapidly eliminated from urine and feces in 0-4 h. The majority of intact sesamol glucuronide was excreted in the urine. It is suggested that sesamol conjugated metabolites are primarily eliminated from the plasma via the kidney by active tubular secretion. LC-MS/MS analyses of rat excreta showed that sesamol can be converted to 2-methoxybenzene-1,4-diol and benzene-1,2,4-triol in vivo by rat.