In this work, a curcumin-diglutaric acid (CurDG) prodrug was synthesized by conjugation of curcumin with glutaric acid via an ester linkage. The water solubility, partition coefficient, release characteristics, and antinociceptive activity of CurDG were compared to those of curcumin. The aqueous solubility of CurDG (7.48 μg/mL) is significantly greater than that of curcumin (0.068 μg/mL). A study in human plasma showed that the CurDG completely releases curcumin within 2 h, suggesting the ability of CurDG to serve as a prodrug of curcumin. A hot plate test in mice showed the highest antinociceptive effect dose of curcumin at 200 mg/kg p.o., whereas CurDG showed the same effect at an effective dose of 100 mg/kg p.o., indicating that CurDG significantly enhanced the antinociceptive effect compared to curcumin. The enhanced antinociceptive effect of CurDG may be due to improved water solubility and increased oral bioavailability compared to curcumin.

No abstract

Previous studies have reported that green tea effectively protects against cancers caused by various dietary carcinogens. As P450 enzymes are the major system responsible for the metabolism of many carcinogens, we hypothesise that tea consumption may alter the catalytic activities of P450 enzymes. We conducted this study to screen the effects of four different teas on the activities of P450 enzymes. Tea solutions (2.5%) were prepared by adding boiling water to tea leaves and filtering. Female Wistar rats were divided into five groups (n = 4 each); each had free access to tea solutions while the control group was supplied with water for 4 weeks. Animals were sacrificed and livers were removed for preparation of microsomes. Enzyme activities were determined by incubation of liver microsomes with the appropriate CYP substrate. The activity of CYP1A1 in livers from rats receiving Oolong (Chinese) tea (185 +/- 63 pmol/mg/min), Japanese green tea (197 +/- 22 pmol/mg/min) and Earl Grey tea (228 +/- 40 pmol/mg/min) was significantly higher (p < 0.05) than in the control group (94 +/- 34 pmol/mg/min), whereas no change was observed in the activity of CYP1A2 in any of tested animals. The hepatic activity of CYP2D6 was greater only in rats drinking Earl Grey tea compared to the controls (235 +/- 37 vs 161 +/- 41 pmol/mg/min, p < 0.05). There were also significant increases (p < 0.05) in the activity of CYP3A in livers of animals given Oolong tea (653 +/- 174 vs 382 +/- 114 pmol/mg/min) and Earl Grey tea (751 +/- 202 pmol/mg/min), while Jasmine and Japanese green tea had no significant effect. These results indicate that not all types of tea cause alterations in liver CYP enzymes as some elevated activities and some did not. Further studies are needed to determine whether there is a relationship between the effect of tea on CYP activities and anti-carcinogenesis.