Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Chin Med. 2009 Sep 25;4:19. doi: 10.1186/1749-8546-4-19.
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.
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 microM were hydrolyzed by porcine liver esterase.
All esters transported across the Caco-2 cell without enzymatic hydrolysis. The apparent permeability coefficients P(app) of compound 1 at 53 microM and 106 microM were 13.94 (0.60) x 10(-6) and 14.33 (0.17) x 10(-6) cm/s respectively, while those of compound 2 were 9.45 (0.29) x 10(-6) and 10.08 (0.32) x 10(-6) cm/s, respectively. Papp values of compound 3 were 7.48 (0.31) x 10(-6) cm/s at 53 microM and 8.60 (0.55) x 10(-6) cm/s at 106 microM. 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) x 10(-6) cm/s at 53 microM and 16.38 (0.61) x 10(-6) cm/s at 106 microM. 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.
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.
蓬莪术根茎和黑种草子是泰式传统医学中缓解痛经和调节月经周期的两种成分。这两种草药的混合物产生了三种酯，即（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-基亚油酸酯（1）、（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-基油酸酯（2）和（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-基棕榈酸酯（3）。本研究旨在研究这些酯在体外的吸收情况，并评估它们的跨膜转运情况。
在 Caco-2 细胞单层中观察这三种酯的体外转运情况。浓度为 10 μM 的酯化合物 1、2 和 3 被猪胰脂肪酶水解。
所有酯均未经酶水解即可穿过 Caco-2 细胞。化合物 1 在 53 μM 和 106 μM 时的表观渗透系数 P(app)分别为 13.94（0.60）×10（-6）和 14.33（0.17）×10（-6）cm/s，而化合物 2 的 P(app)值分别为 9.45（0.29）×10（-6）和 10.08（0.32）×10（-6）cm/s。化合物 3 在 53 μM 时的 P(app)值为 7.48（0.31）×10（-6）cm/s，在 106 μM 时为 8.60（0.55）×10（-6）cm/s。母体化合物（化合物 D），即（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-醇的 P(app)值在 53 μM 时为 8.53（0.83）×10（-6）cm/s，在 106 μM 时为 16.38（0.61）×10（-6）cm/s。化合物 1、2 和 3 由猪胰脂肪酶水解的酯水解通过 HPLC 进行监测，水解反应在 10 分钟内完成。
使用 Caco-2 细胞单层模型，本研究发现，源自蓬莪术根茎和黑种草子的化合物（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-基亚油酸酯（1）、（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-基油酸酯（2）和（E）-4-（3,4-二甲氧基苯基）-3-丁烯-1-基棕榈酸酯（3）可能通过易化机制转运，并作为前药增加血液中化合物 D 的水平。
