Cellular transport of anti-inflammatory pro-drugs originated from a herbal formulation of Zingiber cassumunar and Nigella sativa

BACKGROUND: The rhizome of Zingiber cassumunar and the seed of Nigella sativa are two ingredients in Thai traditional medicine to relieve dysmenorrhea and adjust the menstrual cycle. Mixture of these two herbs produces three esters, namely (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl linoleate (1), (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl oleate (2) and (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl palmitate (3). The aim of this study is to examine in vitro absorption of these esters and evaluate their transport across the membrane. METHODS: In vitro transport of these three esters was observed in Caco-2 cell monolayers. The ester compounds 1, 2 and 3 at a concentration of 10 μM were hydrolyzed by porcine liver esterase. RESULTS: All esters transported across the Caco-2 cell without enzymatic hydrolysis. The apparent permeability coefficients P(app )of compound 1 at 53 μM and 106 μM were 13.94 (0.60) × 10(-6 )and 14.33 (0.17) × 10(-6)cm/s respectively, while those of compound 2 were 9.45 (0.29) × 10(-6 )and 10.08 (0.32) × 10(-6)cm/s, respectively. P(app )values of compound 3 were 7.48 (0.31) × 10(-6)cm/s at 53 μM and 8.60 (0.55) × 10(-6)cm/s at 106 μM. P(app )values of the parent compound (compound D), i.e. (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-ol were 8.53 (0.83) × 10(-6)cm/s at 53 μM and 16.38 (0.61) × 10(-6)cm/s at 106 μM. The ester hydrolysis of compounds 1, 2 and 3 by porcine liver esterase was monitored by HPLC and the hydrolysis reactions were completed within 10 minutes. CONCLUSION: Using the Caco-2 cell monolayer model, the present study finds that compounds (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl linoleate (1), (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl oleate (2) and (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl palmitate (3) originated from Prasaplai preparation (a Thai herbal formula) may be transported through a facilitated mechanism and serve as pro-drugs to increase the compound D level in the blood.