Turmeric is the powdered dry rhizome of the plant Curcuma longa and has been widely used as a coloring agent, as a spice and has been utilized in the treatment of inflammatory conditions and other diseases.1) Curcumin is a yellow pigment and is the major anti-oxidant and anti-inflammatory constituent of turmeric. It is present in curry and mustard, and it is used extensively in Asian countries and in traditional medicines. Curcumin and/or turmeric have both been shown to possess cancer chemopreventive activity in addition to anti-inflammatory activity, and these compounds have thus generated considerable attention as alternative medicines in recent years.2-4) The low incidence of colon cancer in Asian countries could be related to low meat intake, but may also be due to the regular use of turmeric in the diet of these regions. As the colon is exposed to turmeric and curcumin, it is a likely target for the anticarcinogenic activity of these compounds. Moreover, since these agents are often administered in combination with conventional therapeutic drugs, it is very important to further explore the potential benefits of herb-drug interactions. Previously we have investigated such herb-drug interactions at the level of conjugation. 5,6) We have also recently established an assay system for conjugation reactions of 1-naphthol using a human adenocarcinoma cell line, Caco-2.7) In our current study, to elucidate the possible interaction of both turmeric and curcumin with the conjugation pathways in cells, which in many cases are involved in the activation of procarcinogens, we measured their effects on the conjugation activity of 1-naphthol in Caco-2 cells. MATERIALS AND METHODS MaterialsPowdered turmeric was obtained from Wako, Ltd. and curcumin was purchased from Sigma. Water-soluble and DMSO-soluble turmeric solutions were prepared by stirring turmeric powder (10 g) in either 100 ml distilled water or DMSO for 3 h at room temperature. Each solution was then filtered.Cell Culture Human adenocarcinoma Caco-2 cells were grown in 12-well plates in 1 ml minimal essential medium (MEM) supplemented with 10% fetal bovine serum and additional non-essential amino acids. The cells were seeded at 5ϫ10 5 cells/ml and cultured for up to 3 weeks with medium changes every 4-5 d.Analyses of 1-Naphthyl Sulfates and Glucuronide 1-Naphthol (200 mM) was added to the culture medium and the cells were further incubated at 37°C. Aliquots of 50 ml of medium were removed at various times, and 30 ml of each of these samples was then filtered and injected into a HPLC apparatus, equipped with an ODS column (Chromolith Performance RP-18e, 100ϫ4.6 mm, Merck). The mobile phase consisted of 2 mM tetrabutylammonium hydrogen sulfate in water and acetonitrile (65 : 35). The flow rate was 1.0 ml/min with a column temperature of 40°C and elution was monitored at 285 nm. The retention times for 1-naphthol, 1-naphthyl sulfate and 1-naphthyl glucuronide were determined to be 19.0 min, 17.6 min and 4.6 min, respectively. The effects of curcumin or turmeric o...

Several fruit juices have been reported to cause food-drug interactions, mainly affecting cytochrome P450 activity; however, little is known about the effects of fruit juices on conjugation reactions. Among several fruit juices tested (apple, peach, orange, pineapple, grapefruit, and pomegranate), pomegranate juice potently inhibited the sulfoconjugation of 1-naphthol in Caco-2 cells. This inhibition was both dose- and culture time-dependent, with a 50% inhibitory concentration (IC(50)) value calculated at 2.7% (vol/vol). In contrast, no obvious inhibition of glucuronidation of 1-naphthol in Caco-2 cells was observed by any of the juices examined. Punicalagin, the most abundant antioxidant polyphenol in pomegranate juice, was also found to strongly inhibit sulfoconjugation in Caco-2 cells with an IC(50) of 45 microM, which is consistent with that of pomegranate juice. These data suggest that punicalagin is mainly responsible for the inhibition of sulfoconjugation by pomegranate juice. We additionally demonstrated that pomegranate juice and punicalagin both inhibit phenol sulfotransferase activity in Caco-2 cells in vitro, at concentrations that are almost equivalent to those used in the Caco-2 cells. Pomegranate juice, however, shows no effects on the expression of the sulfotransferase SULT1A family of genes (SULT1A1 and SULT1A3) in Caco-2 cells. These results indicate that the inhibition of sulfotransferase activity by punicalagin in Caco-2 cells is responsible for the reductions seen in 1-naphthyl sulfate accumulation. Our data also suggest that constituents of pomegranate juice, most probably punicalagin, impair the enteric functions of sulfoconjugation and that this might have effects upon the bioavailability of drugs and other compounds present in food and in the environment. These effects might be related to the anticarcinogenic properties of pomegranate juice.

Low birth weight has been associated with cardiovascular diseases. The waist-to-height ratio is a good indicator of risks for these diseases. The objective of this study was to examine the associations between birth weight and adult waist-to-height ratio in a Japanese population. A cross-sectional study, comprised of 851 subjects (401 men and 450 women) aged 35-62 years who were born at full term, was conducted at a medical checkup. The subjects responded to a questionnaire about weight at birth, and data on physical characteristics were collected from the results of the medical checkup. The subjects were stratified with sex and a Body Mass Index of 25 kg/m 2 to elucidate the effects of birth weight on adult waist-to-height ratio. Analysis of covariance was used to compare the physical condition among the 4 birth weight categories. After adjusting for age, alcohol consumption, smoking status and exercise, the height was significantly lower in the birth weight < 2,500 g category among men (P < 0.001) and women (P < 0.001), while the waist-to-height ratio was significantly higher in the birth weight < 2,500 g category, compared with the > 3,500 g category in the non-obese women (P = 0.004), but not in the obese women. In conclusion, low birth weight was independently associated with a low adult height among men and women and with a high adult waist-to-height ratio among non-obese women. Our results suggest that intrauterine environmental insults might lead to accumulation of visceral fat among non-obese women.

To investigate the possible effects of different beverages in the gastrointestinal tract on the sulfation of estrogen, which is a major hormone and prototype substrate for the human sulfotransferases (SULT), we analyzed the effects of these substances upon the sulfate conjugation of 17b b-estradiol (E 2 ) in the human colon carcinoma cell line Caco-2. Sulfoconjugation activity toward E 2 was measured by incubating 20 nM E 2 with Caco-2 cells in the presence (5% (v/v)) of each beverage. Among the 35 beverages analyzed, four (aronia, blueberry, coffee, and peppermint) exhibited strong inhibitory effects on E 2 sulfation within Caco-2 cells (IC 50 values ranging from 1.9 to 4.4% (v/v)). These active beverages also strongly inhibited the cytosolic estrogen SULT activity of Caco-2 cells in vitro (IC 50 values ranging from 0.18 to 0.3% (v/v)). These inhibitory activities were extractable with ethyl acetate but not hexane or n-butanol, indicating that the molecules responsible are moderately lipophilic. Coffee was found to be the most potent inhibitor but the major constituents of this beverage, caffeic acid, caffeine, and chlorogenic acid, did not show any effects on estrogen SULT activity. Kinetic analyses further indicated that the mode of inhibition by coffee is competitive. A possible relationship between the inhibition of estrogen SULT activity by coffee in the gastrointestinal tract and the reported reduction of colon cancer incidence in women who consume coffee is discussed.

Recently, in Japan, the percentage of leanness has risen in young women, and the average birth weight has decreased. An increase in the risk of low birth weight has been reported in lean expectant mothers. In this study, we aimed to clarify the relationship between mother's physique at the beginning of pregnancy and the infant's physique, by focusing on sex differences. The participants were 3,722 mothers who attended health checkups for 18-month-old infants in an urban Japanese city. The participants were limited to those with full-term births, thereby excluding the influence of gestational length. A total of 1,287 mothers, with 621 boys and 666 girls, were analyzed. Public health professionals interviewed the mothers, and transferred the required information from their maternity passbooks. We examined the physical characteristics of the mothers and their infants. Partial correlation analysis, adjusted by gestational length and the mother's age at delivery, was applied to study the association between the mother's BMI and the infant's physique at birth. In the primipara group, only the boys showed significant positive correlation between the mother's BMI and the birth weight (P = 0.025) and the Kaup index (P = 0.035). In the pluripara group, only the boys showed significant positive correlation between the mother's BMI and the head circumference (P = 0.035). Thus, mother's physique may have a stronger influence on the physique of male infants, compared to female infants. The growth-promoting effect of the mother's physique is more apparent in the infants born to the pluripara.