14-Benzoylaconine

Multidrug resistance-associated protein 2 is involved in the efflux of Aconitum alkaloids determined by MRP2-MDCKII cells.[Pubmed: 25744397]

Life Sci. 2015 Apr 15;127:66-72.

Aconitum alkaloids mainly contain highly toxic aconitine (AC), mesaconitine (MA), and hypaconitine (HA) and less toxic Benzoylaconine (BAC), benzoylmesaconine (BMA), benzoylhypaconine (BHA), aconine, mesaconine, and hypaconine. The efflux transporters including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2) can efflux toxicants to prevent poisoning. Our previous publication has proved that P-gp and BCRP contributed to the efflux of AC, MA and HA, which is demonstrated in the human colonic adenocarcinoma cell lines (Caco-2 cells), Mardin-Darby canine kidney cell lines transfected with MDR1 or BCRP (MDR1-MDCKII and BCRP-MDCKII cells). However, the role of MRP2 remains uncertain.
METHODS AND RESULTS:
The MRP2-MDCKII cells were used to determine the efflux ratios (Er) and intracellular amounts of Aconitum alkaloids. In addition, the importance of MRP2 was further investigated with or without the MRP2 inhibitor, LTC4. The Er values of AC, MA, HA, BAC, BMA and BHA in MRP2-MDCKII cells (6.4 ± 0.3, 5.9 ± 0.5, 2.2 ± 0.2, 1.6 ± 0.3, 1.7 ± 0.2 and 1.9 ± 0.2 respectively) were significantly higher than those in MDCKII cells, which were close to 1. In the presence of LTC4, the Er values of AC, MA, HA, BAC, BMA and BHA were reduced to approximately 1 and their intracellular amounts were also significantly increased in MRP2-MDCKII cells.
CONCLUSIONS:
MRP2 was involved in the efflux of AC, MA, HA, BAC, BMA and BHA, which would be useful for the safe application of these components or their herbs.

Metabolomics Study of Aconitine and Benzoylaconine Induced Reproductive Toxicity in BeWo Cell. [Reference: WebLink]

Chinese J. Anal. Chem., 2015, 43(12):1808-13.

An intracellular metabolomics method based on gas chromatography coupled with mass spectrometry (GC-MS) was established to explore the toxicity mechanism of aconitine and Benzoylaconine. BeWo, a continuous cell lines originated from human placenta, was selected to establish in vitro placenta model.
METHODS AND RESULTS:
The intracellular metabolites were extracted after exposed to 5 μg mL−1 aconitine and Benzoylaconine for 0, 6, 12, 24 and 36 h, respectively. The intracellular metabolic profiles were acquired by GC-MS. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plot showed the time-dependent change of the metabolomic profiles between the control and intervention groups. After screening by variable influence on projection (VIP) value and one-way analysis of variance, and searching with NIST 2014 database, 11 metabolites were identified, including proline, glycine, threonine, glutamic acid, N-acetylglutamine, glutamine, lysine, histidine, succinic acid, glucose and galactose, which were mainly involved in the following pathways: (1) glutamine and glutamate metabolism; (2) glycine, serine and threonine metabolism; (3) alanine, aspartate and glutamate metabolism; (4) lysine degradation; (5) arginine and proline metabolism and (6) histidine metabolism.
CONCLUSIONS:
The results demonstrated that amino acid metabolism was the main metabolic pathway and responsible for the placental and fetal toxicity of aconitine and Benzoylaconine.