Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Abstract

Aconitine (AC), benzoylaconine (BAC), and aconine (ACN) are three representative alkaloids in Aconitum tubers. Knowing that the drug disposal process in vivo is closely related to the toxicity and efficacy of a drug, it is important to classify the disposal properties of these alkaloids. In this study, the pharmacokinetics of the three alkaloids was investigated. The results showed that the three alkaloids could be quickly absorbed, especially BAC, whose Tmax was 0.31 ± 0.17 h. Their Cmax was 10.99, 3.99, and 4.29 ng·mL(-1) respectively, indicating that AC had better absorption than BAC and ACN. Subsequently, we further investigated their absorption mechanism using the Caco-2 cell monolayer model in vitro. The results showed that they were poorly absorbed, and the absorption of AC and BAC was inhibited by P-gp, while the absorption of ACN was in a form of passive diffusion. The t1/2 of AC, BAC and ACN was 1.41, 9.49, and 3.32 h, respectively, indicating that the metabolic or excretion rate of AC was quicker than that of BAC and ACN. Therefore, their metabolic stability was further investigated by using rat liver microsomes in vitro, which showed that AC was easier to be metabolized than BAC and ACN. The excretion experiments showed that AC and ACN were primarily excreted in urine, while BAC was excreted in faeces. In addition, the results of tissue distribution experiments showed that the three alkaloids distributed throughout all the organs, although the distribution rate of AC was slower than that of BAC and ACN. Copyright © 2015 John Wiley & Sons, Ltd.

The In Vivo Evaluation on Total Components from Extract of Aconitum Based on a New Analytic Method of Area under Absorbance-Wavelength Curve

“…e results further demonstrated that the absorption and excretion of total components in rats were rather rapid, which were characterized by the one-compartment model in this study, and they were consistent with the results in the studies [22,[40][41][42]. From Table 6, there was no signi cant di erence (P > 0.05) in those pharmacokinetic parameters between the single-dose group and multiple-dose group.…”

“…ere were many pharmacokinetic studies on Aconitum from references [21][22][23][24] but still lacking of related information for total components of Aconitum. It was reported that Aconitum alkaloids were absorbed and metabolized in vivo rapidly, which were all based on some certain individual alkaloids with clear chemical structure such as aconitine, meaconitine, and hyaconitine by high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (HPLC-MS) [25][26][27].…”

Pharmacokinetic effects of ginsenoside Rg1 on aconitine, benzoylaconine and aconine by UHPLC–MS/MS

“…It was first recorded in Jisheng Xufang (He et al, ; Wei, Wu, Yu, Yan, & Zhang, ). Aconite has long been used in the clinic because of its analgesic, anti‐inflammatory, local anesthetic and anti‐epileptic activities (He et al, ; Suzuki et al, ; Zhang et al, ). At present, aconite is often used for the treatment of acute myocardial infarction, hypotension, coronary heart disease, chronic heart failure and other shocks in combination with other traditional Chinese herbal medicines.…”

Relationships between the Toxicities of Radix Aconiti Lateralis Preparata (Fuzi) and the Toxicokinetics of Its Main Diester-Diterpenoid Alkaloids

“…The liver and the kidney are the two major organs that AC is preferably distributed to, followed by the heart, blood, the spleen, and the lung [ 21 , 49 ]. In the liver, kidney, and heart, AC reached a peak concentration at around 10–240 min [ 21 , 49 , 50 ]. In one study, muscle was also found as a major tissue containing AC [ 50 ].…”

“…In the liver, kidney, and heart, AC reached a peak concentration at around 10–240 min [ 21 , 49 , 50 ]. In one study, muscle was also found as a major tissue containing AC [ 50 ]. Due to the blood–brain barrier, only a trace amount of AC was found in brain tissue [ 49 ].…”