Pharmacy College, Chengdu University of Traditional Chinese Medicine, Wenjiang District 1166, Chengdu City, Sichuan, PR China.
J Ethnopharmacol. 2013 May 2;147(1):128-35. doi: 10.1016/j.jep.2013.02.019. Epub 2013 Mar 16.
Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating.
In present study, we focus on Fuzi-Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi-Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated.
Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed.
In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1(st) order absorption and lag time.
Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi-Gancao herb-pair.
乌头属植物（附子，在中国被称为 Fuzi）在临床上被广泛用于治疗心力衰竭和风湿病。然而，由于其严重的毒性，甘草（在中国被称为 Gancao）与它一起被用作中药（TCM）药对，以降低毒性并提高药理作用。尽管已经有一些关于这方面的观点被报道，但这两种草药的潜在相互作用机制仍然未知，这肯定值得研究。
在本研究中，我们专注于附子-甘草药对沉淀（FGP），因为它与附子-甘草药对的配伍机制有关。研究了沉淀中 3 种二酯二萜生物碱的肠吸收和药代动力学特征。
采用外翻肠囊模型和原位肠灌流模型研究了乌头碱、次乌头碱和新乌头碱在大鼠小肠中的通透性和转运机制。此外，通过测定血浆浓度，建立了 3 种生物碱在大鼠体内的药代动力学特征。
在外翻肠囊通透性实验中，次乌头碱在回肠中的通透性最好。此外，在 P-糖蛋白（P-gp）抑制剂存在的情况下，它们的摄取量增加。在原位肠灌流摄取实验中，结果表明其转运机制可能符合主动转运机制。并且 FPG 中的 3 种生物碱在大鼠体内能很好地吸收，符合 2 室模型，具有 1（st）级吸收和滞后时间。
本研究结果表明，FGP 中的 3 种二酯二萜生物碱在口服后可首先溶解在胃肠道中，然后被吸收到血液中，从而延长其平均停留时间并增加其吸收剂量，避免剂量倾倒。本研究对进一步研究其他酸碱药对以及附子-甘草药对的相互作用机制具有重要的启示意义。
