Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat.

Tangeretin, 4',5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 µg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects.

Hyperimmune colostrum alleviates rheumatoid arthritis in a collagen-induced arthritis murine model.

Our aging population and the accompanying decline in immune function is a growing concern that may be addressed by finding natural methods to enhance the immunocompetence of our elderly. Bovine milk and colostrum from cows that have been immunized have been shown to provide additional immunoglobulins and other bioactive molecules that enhance immune function. The purpose of this study was to investigate the ability of hyperimmune bovine colostrum to alleviate the symptoms of rheumatoid arthritis in a murine model. The collagen-induced arthritis DBA/1J murine model was used for this study. Mice were fed colostrum from immunized cows at either 5 or 10 mg/mouse per day or controls for 49 d. The data showed that the colostrum-fed groups had significantly lower total swelling scores and significantly lower collagen-specific antibody (IgG2a), inflammation-associated antibody (total IgG), and the inflammatory cytokines tumor necrosis factor α, IL-2, IL-6, and IFN-γ. The results strongly suggest that colostrum from immunized cows may have anti-inflammatory activity in a mouse model of rheumatoid arthritis.

Protective effect of Nelumbo nucifera extracts on beta amyloid protein induced apoptosis in PC12 cells, in vitro model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. ß-Amyloid (Aß) has been proposed to play a role in the pathogenesis of AD. Deposits of insoluble Aß are found in the brains of patients with AD and are one of the pathological hallmarks of the disease, but the underlying signaling pathways are poorly understood. In order to develop antidementia agents with potential therapeutic value, we examined the inhibitory effect of the Nelumbo nucifera seed embryo extracts on to the aggregated amyloid ß peptide (agg Aß1-40)-induced damage of differentiated PC-12 cells (dPC-12), a well-known cell model for AD. In the present study, seed embryos of N. nucifera were extracted with 70% methanol in water and then separated into hexane, ethyl acetate, n-butanol, and water layers. Among them, only the n-butanol layer showed strong activity and was therefore subjected to separation on Sephadex LH-20 chromatography. Two fractions showing potent activity were found to significantly inhibit Aß1-40 toxicity on dPC-12 cells in increasing order of concentration (10-50 µg/mL). Further purification and characterization of these active fractions identified them to be flavonoids such as rutin, orientin, isoorientin, isoquercetrin, and hyperoside. 2,2-Diphenyl-1-picrylhydrazyl hydrate scavenging activity of the extracts was also carried out to ascertain the possible mechanism of the activity.

Proteomic changes associated with metabolic syndrome in a fructose-fed rat model.

Metabolic syndrome (MetS), characterized by a constellation of disorders such as hyperglycemia, insulin resistance, and hypertension, is becoming a major global public health problem. Fructose consumption has increased dramatically over the past several decades and with it the incidence of MetS. However, its molecular mechanisms remain to be explored. In this study, we used male Sprague-Dawley (SD) rats to study the pathological mechanism of fructose induced MetS. The SD rats were fed a 60% high-fructose diet for 16 weeks to induce MetS. The induction of MetS was confirmed by blood biochemistry examination. Proteomics were used to investigate the differential hepatic protein expression patterns between the normal group and the MetS group. Proteomic results revealed that fructose-induced MetS induced changes in glucose and fatty acid metabolic pathways. In addition, oxidative stress and endoplasmic reticulum stress-related proteins were modulated by high-fructose feeding. In summary, our results identify many new targets for future investigation. Further characterization of these proteins and their involvement in the link between insulin resistance and metabolic dyslipidemia may bring new insights into MetS.

Food Safety Program in Asian Countries.

By using the ILSI network in Asia, we are holding a session focused on food safety programs in several Asian areas. In view of the external environment, it is expected to impact the global food system in the near future, including the rapid increase in food demand and in public health services due to population growth, as well as the threats to biosecurity and food safety due to the rapid globalization of the food trade. Facilitating effective information sharing holds promise for the activation of the food industry. At this session, Prof. Hwang shares the current situation of Food Safety and Sanitation Regulations in Taiwan. Dr. Liu provides a talk on the role of risk assessment in food regulatory control focused on aluminum-containing food additives in China. After the JECFA evaluation of aluminum-containing food additives in 2011, each country has carried out risk assessment based on dietary intake surveys. Ms. Chan reports on the activities of a working group on Food Standards Harmonization in ASEAN. She also explains that the ILSI Southeast Asia Region has actively supported the various ASEAN Working Groups in utilizing science to harmonize food standards. Prof. Park provides current research activities in Korea focused on the effect of climate change on food safety. Climate change is generally seen as having a negative impact on food security, particularly in developing countries. We use these four presentations as a springboard to vigorous discussion on issues related to Food Safety in Asia.

Biotransformation of ginsenoside Rd in the ginseng extraction residue by fermentation with lingzhi (Ganoderma lucidum).

Ginseng and lingzhi (Ganoderma lucidum) both are valuable traditional Chinese medicines and have been extensively utilised in functional foods and traditional medicines in many Asian countries. However, massive quantity of ginseng residue is produced after extraction of ginseng which still contains a lot of bioactive compounds such as ginsenosides. The goal of this study was to reuse the American ginseng extraction residue as the fermentation medium of G. lucidum to produce bioactive ginsenoside enriched biotransformation products. The changes of ginsenosides in the fermentation products were analysed during fermentation. Our results showed that after 30 days of fermentation, ginsenoside Rg1, Rd, and compound K (CK) significantly increased, especially Rd, while other ginsenosides (Re, Rb1 and Rc) decreased during fermentation. Ginsenoside Rd is the major ginsenoside in the final fermentation product. Furthermore, the biotransformation of ginsenosides was the major reaction in this fermentation process.

Identification of sinensetin metabolites in rat urine by an isotope-labeling method and ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry.

Sinensetin (SIN), one of the major polymethoxyflavones (PMFs) contained mainly in the citrus peels, has been reported to possess various bioactivities, including antifungal, antimutagenic, anticancer, and anti-inflammatory activities. Although the biotransformation of SIN in fungi and insects has been reported, the information about the metabolism of SIN in mammals is still unclear. In this study, formation of SIN metabolites in rats was investigated. Four isotope-labeled SINs ([4'-D3]SIN, [3'-D3]SIN, [5-D3]SIN, and [6-D3]SIN) were synthesized and administered to rat. The urine samples were collected and main metabolites were monitored by ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. The administered compound and four SIN metabolites were detected in rat urine. These metabolites were identified as 4'-hydroxy-5,6,7,3'-tetramethoxyflavone, 5-hydroxy-6,7,3',4'-tetramethoxyflavone, 6-hydroxy-5,7,3',4'-tetramethoxyflavone, and 7-hydroxy-5,6,3',4'-tetramethoxyflavone sulfate.

Tissue distribution and cytochrome P450 inhibition of sesaminol and its tetrahydrofuranoid metabolites.

Sesame lignans such as sesamin, sesaminol, and sesamolin are major constituents of sesame oil, and all have a methylenedioxyphenyl group and multiple functions in vivo. It was previously reported that sesaminol, a tetrahydrofurofuran type lignin, was metabolized to mammalian lignans. The present study examined the tissue distribution of sesaminol in Sprague-Dawley (SD) rats. Changes in the concentration of sesaminol and its metabolites (sesaminol glucuronide/sulfate, hydroxymethylsesaminol-tetrahydrofuran, enterolactone, and enterodiol) were determined in tissues within a 24 h period after tube feeding (po 220 mg/kg) to SD rats. The concentrations of enterodiol and enterolactone were significantly higher than those of sesaminol and its tetrahydrofuranoid metabolites in the organs (liver, heart, brain, and kidney). This study demonstrates that sesaminol has potent inhibition of cytochrome P450 (CYPs), compared to tetrahydrofuranoid metabolites. The IC(50) values of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 for sesaminol were determined as 3.57, 3.93, 0.69, 1.33, and 0.86 µM, respectively. In addition, hydroxymethylsesaminol-tetrahydrofuran and enterodiol were weak inhibitors of CYP2C9 and CYP1A2, respectively.

Neuroprotective effects of longan ( Dimocarpus longan Lour.) flower water extract on MPP+-induced neurotoxicity in rat brain.

In this study, the neuroprotective effect of Dimocarpus longan Lour. flower water extract (LFWE) was investigated. First, an in vitro study showed that LFWE concentration-dependently inhibited lipid peroxidation of brain homogenates incubated at 37 °C. The antioxidative activity of LFWE was more potent than that of glutathione or Trolox. Furthermore, an ex vivo study found that the basal lipid peroxidation (0 °C) and lipid peroxidation incubated at 37 °C were lower in the brain homogenates of LFWE-treated (500 mg/day) rats, indicating that the brain of LFWE-treated rats was more resistant to oxidative stress. Moreover, a Parkinsonian animal model was employed to demonstrate that oral administration of LFWE (125-500 mg/kg/day) dose-dependently attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in the nigrostriatal dopaminergic system of rat brain. In conclusion, this study suggests that LFWE is antioxidative, anti-inflammatory, and anti-apoptotic. Furthermore, oral administration of LFWE appears to be useful in preventing and/or treating central nervous system neurodegenerative diseases, including Parkinsonism.

Identification of 5,7,3',4'-tetramethoxyflavone metabolites in rat urine by the isotope-labeling method and ultrahigh-performance liquid chromatography-electrospray ionization-mass spectrometry.

5,7,3',4'-Tetramethoxyflavone (TMF), one of the major polymethoxyflavones (PMFs) isolated from Kaempferia parviflor , has been reported possessing various bioactivities, including antifungal, antimalarial, antimycobacterial, and anti-inflammatory activities. Although several studies on the TMF have been reported, the information about the metabolism of TMF and the structures of TMF metabolites is still not yet clear. In this study, an isotope-labeling method was developed for the identification of TMF metabolites. Three isotope-labeled TMFs (5,7,3',4'-tetramethoxy[3'-D(3)]flavone, 5,7,3',4'-tetramethoxy[4'-D(3)]flavone, and 5,7,3',4'-tetramethoxy[5,4'-D(6)]flavone) were synthesized and administered to rats. The urine samples were collected, and the main metabolites were monitored by ultrahigh-performance liquid chromatography-electrospray ionization-mass spectrometry. Five TMF metabolites were unambiguously identified as 3'-hydroxy-5,7,4'-trimethoxyflavone, 7-hydroxy-5,3',4'-trimethoxyflavone sulfate, 7-hydroxy-5,3',4'-trimethoxyflavone, 4'-hydroxy-5,7,3'-trimethoxyflavone, and 5-hydroxy-7,3',4'-trimethoxyflavone.

Transformation of proanthocyanidin A2 to its isomers under different physiological pH conditions and common cell culture medium.

Proanthocyanidins constitute an important class of polyphenols ubiquitously found in plants. They have been extensively studied for their antioxidant capacity and bioactivity in vitro and in animal models. However, their stability under different pH conditions and in cell culture medium has not been well documented. In the present study, it was observed that proanthocyanidin A2 (PA2) was relatively more stable in acidic condition than in weak alkaline condition. PA2 was also quite unstable in basal-Dulbecco's Modified Eagle medium (b-DMEM medium) at 37 °C. The addition of PA2 to the cell culture medium accelerated its epimerization with a half-life of <15 min, and ethylenediaminetetraacetic acid (EDTA) could not stop the reaction. The results also demonstrated that the major isomers transformed in the weak alkaline condition or cell culture medium at 37 °C were identified as epicatechin-(4ß→8; 2ß→O→7)-ent-catechin (proanthocyanidin A4) and epicatechin-(4ß→6; 2ß→O→7)-ent-catechin. The rates of transformation were dependent on the pH or the components of the medium. Therefore, the results obtained for PA2 in the cell culture bioassays, which were usually carried out for 24 h, might not represent the true activity of the original PA2. The stability and transformation of PA2 should be considered when the bioactivity of PA2 is evaluated in a given cell culture system.

Intestinal distribution and excretion of sesaminol and its tetrahydrofuranoid metabolites in rats.

Sesame seeds (Sesamum indicum L.) are unique because of potent and various physiological activities imparted by their bioactive lignans. This investigation studied the intestinal distribution and excretion of sesaminol in Sprague-Dawley (SD) rats. To investigate the distribution of sesaminol (per oral 220 mg/kg), the changes in concentration of sesaminol and its metabolites were determined in the intestines and plasma within the 24 h period after tube feeding of sesaminol to SD rats. Results show that the epimerization of sesaminol appeared to be catalyzed by acid in the simulated gastric fluids. The major sesaminol epimer was characterized as 2-episesaminol using 2D-NMR. These findings indicate that sesame sesaminol and its epimer are poorly absorbed prior to reaching the rectum and that substantial amounts pass from the small to the large intestine, where they are metabolized by the colonic microflora to tetrahydrofuranoid metabolites. Sesaminol in plasma was largely present as phase II conjugates, and the seven metabolites were detected as the 2-episesaminol, sesaminol-6-catechol, methylated sesaminol-catechol, R,R-hydroxymethylsesaminol-tetrahydrofuran, S,R-hydroxymethylsesaminol-tetrahydrofuran, enterolactone, and enterodiol. Excretions of sesaminol in urine and feces within the 24 h period were equivalent to 0.02 and 9.33% of the amount ingested, respectively.

Blazeispirol A from Agaricus blazei fermentation product induces cell death in human hepatoma Hep 3B cells through caspase-dependent and caspase-independent pathways.

Currently, liver cancer is a leading cause of cancer-related death in the world. Hepatocellular carcinoma is the most common type of liver cancer. Previously, it was reported that blazeispirol A (BA) is the most active antihepatoma compound in an ethanolic extract of Agaricus blazei fermentation product. The aim of this study was to understand the antihepatoma mechanism of BA in human liver cancer Hep 3B cells. The results showed that BA inhibited the growth of Hep 3B cells and increased the percentage of cells in sub-G1 phase in a concentration- and time-dependent manner. In addition, BA treatment resulted in DNA fragmentation, caspase-9 and caspase-3 activations, poly(ADP-ribose)polymerase (PARP) degradation, down-regulation of Bcl-2 and Bcl-xL expressions, up-regulation of Bax expression, and disruption of the mitochondrial membrane potential (MMP) in Hep 3B cells. Furthermore, z-VAD-fmk, a caspase inhibitor, did not enhance the viability of BA-treated Hep 3B cells, and BA induced the release of HtrA2/Omi and apoptosis-inducing factor (AIF) from mitochondria into the cytosol. These findings suggested that BA with novel chemopreventive and chemotherapeutic potentials causes both caspase-dependent and caspase-independent cell death in Hep 3B cells.

Inhibitory activity of natural occurring antioxidants on Thiyl radical-induced trans-arachidonic acid formation.

trans-Fatty acids in humans not only may be obtained exogenously from food intake but also could be generated endogenously in tissues. The endogenous generation of trans-fatty acids, especially in the cell membranes induced by radical stress, is an inevitable source for the living species. Thiyl radicals generated from thiols act as the catalyst for the cis-trans isomerization of fatty acids. Arachidonic acid (5c,8c,11c,14c-20:4) with only two of the four double bonds deriving from linoleic acid in the diet can be used to differentiate the exogenous or endogenous formation of double bonds. The aim of this study is to evaluate the effective compounds in preventing thiyl radical-induced trans-arachidonic acid formation during UV irradiation in vitro. The trans-arachidonic acids were found to be 75% after 30 min UV irradiation of all-cis-arachidonic acid. Myricetin, luteolin, and quercetin had the highest thiyl radical scavenging activities, whereas sesamol, gallic acid, and vitamins A, C, and E had the lowest. The structures of flavonoids with higher thiyl radical scavenging activities were a 3',4'-o-dihydroxyl group in the B ring and a 2,3-double bond combined with a 4-keto group in the C ring. These effective compounds found in the present work may be used as lead compounds for the potential inhibitors in the formation of trans-fatty acids in vivo.

Effect of fermentation time on antioxidative activities of Ganoderma lucidum broth using leguminous plants as part of the liquid fermentation medium.

Oxidative damage plays an important role in the pathology of human diseases. Ganoderma lucidum, a medicinal fungus, has been used for thousands of years in traditional Oriental medicine. It is reported to have antioxidant functions such as inhibition of lipid peroxidation. The objective of the present study was to investigate the effect of fermentation time on the antioxidative activities of G. lucidum broth filtrate using leguminous plants as part of the liquid fermentation medium. Inhibition of Cu(2+)-induced oxidation of human low-density lipoprotein (LDL), DPPH radical-scavenging activity, total phenolic compounds, isoflavones and protocatechuic acid were measured to evaluate the antioxidant activity of G. lucidum fermentation broth filtrate. Our results showed that black soybean and Astragalus membranaceus improved the antioxidant activity of the G. lucidum fermentation broth filtrate. Protocatechuic acid was identified by LC-MS as the antioxidant compounds whose relative potency of inhibiting LDL oxidation to Trolox is 1.55. Protocatechuic acid showed positive correlation with the antioxidant activity of the fermentation broth filtrate while isoflavones did not contribute to antioxidant activity.

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.

Tissue distribution and elimination of sesaminol triglucoside and its metabolites in rat.

Sesame exhibits many beneficial physiological effects, which are mostly related to its lignan compounds, such as sesaminol glucosides. This investigation studies the distribution and elimination of sesaminol triglucoside from sesame in Sprague Dawley (SD) rats. In order to investigate the distribution of sesaminol triglucoside (p.o. 500 mg/kg) in SD rats, the changes in concentration of sesaminol triglucoside and its metabolites were determined in tissues and plasma within 24 h period after tube-feeding to SD rats. Results showed that sesaminol triglucoside may be deglycosylated to form sesaminol first by intestinal microflora and then incorporated via lymphatic absorption into the cardiovascular system, transported to other tissues. The concentrations of sesaminol triglucoside and its metabolites in rectum, caecum, colon, and small intestines are higher than those in liver, lung, kidney, and heart. Its concentration in brain is low but detectable. Glucuronidation and sulfation was the main metabolic pathway for sesaminol in urine, and fecal elimination was a major route of elimination. From LC/MS/MS analysis of rat organs, sesaminol triglucoside can be converted to mammalian lignans, enterodiol (END), and enterolactone (ENL), by rat intestinal microflora. In the plasma, concentrations of END and ENL were 5.9 +/- 0.2 and 5.5 +/- 0.2 micromol/mL, respectively.

Biotransformation of sesaminol triglucoside to mammalian lignans by intestinal microbiota.

Plant lignans occur widely in foods, with flaxseed recognized as their richest source. Some plant lignans can be converted by intestinal microbiota to the mammalian lignans, enterodiol and enterolactone, which may have protective effects against hormone-related diseases such as breast cancer. This study determined whether plant lignans in sesame seed, particularly sesaminol triglucoside (STG), could be metabolized to mammalian lignans. STG is a furofuran lignan with methylenedioxyphenyls. The transformation of furofuran lignans to mammalian lignans by intestinal microbiota involves the hydrolysis of glucoside, demethylenation of a methylene group, oxidation of dibenzylbutanediol to dibenzylbutyrolactone, and reductive cleavage of furofuran rings. STG has methylenedioxyphenyl moieties in their structures that may require additional oxidative demethylenation of the methylenedioxyphenyl ring for conversion to mammalian lignans. However, STG is metabolized, via intestinal microbiota, to a catechol moiety. The major STG metabolite was characterized as 4-[((3R,4R)-5-(6-hydroxybenzo[d][1,3]dioxol-5-yl)-4-(hydroxymethyl)tetrahydrofuran-3-yl)methyl]benzene-1,2-diol using NMR and mass spectrometry, and STG could be converted to enterolactone and enterodiol by rat intestinal microflora.

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.