ACONINE

In vivo, aconine is toxic to mice when administered intravenously at a dose of 120 mg/kg. It induces flaccid paralysis and toxicity in rats with toxic dose (TD50) and LD50 values of 1.5 and 1.7 μmol per animal, respectively.

Aconine is an alkaloid originally isolated from Aconitum species and active metabolite of aconitine. It inhibits osteoclast differentiation of RANKL-stimulated RAW 264.7 cells and bone resorption in a pit formation assay in a concentration-dependent manner. Aconine also inhibits RANKL-induced activation of NF-κB and NFATc1 in RAW 264.7 cells.

Aconine is an alkaloid originally isolated from Aconitum species and active metabolite of aconitine. It inhibits osteoclast differentiation of RANKL-stimulated RAW 264.7 cells and bone resorption in a pit formation assay in a concentration-dependent manner. Aconine also inhibits RANKL-induced activation of NF-κB and NFATc1 in RAW 264.7 cells. In vivo, aconine is toxic to mice when administered intravenously at a dose of 120 mg/kg. It induces flaccid paralysis and toxicity in rats with toxic dose (TD₅₀) and LD₅₀ values of 1.5 and 1.7 μmol per animal, respectively.

Aconine is a derivative of Aconitine (A189875), a neurotoxin which activates tetrodotoxin-sensitive Na+ channels, inducing presynaptic depolarization, thus blocking the nerve action potential which, in turn, blocks the release of neurotransmitters and decreases the end plate potential at the neuromuscular junction.

ChEBI: Aconine is a diterpene alkaloid with formula C25H41NO9 that is isolated from several Aconitum species. It has a role as a plant metabolite, a human urinary metabolite, a NF-kappaB inhibitor and a xenobiotic. It is a bridged compound, a diterpene alkaloid, an organic heteropolycyclic compound, a polyether, a tertiary amino compound, a pentol, a secondary alcohol and a tertiary alcohol. It derives from a hydride of an aconitane.

1) Extraction: the main component in the CaoWu is aconitine alkaloids, the dried CaoWu tuberous roots about 4.8kg crushed to about 1 ~ 2 sieve, crushed particles are divided into 6L of the dispensing funnel, with 1000mL 25% ammonia immersion herbs for 2 ~ 4 hours, and then dichloromethane soak CaoWu granular herbs, immersion for 24 hours, every two days percolation, a total of 4 times extraction, decompression recovery The solvent was recovered under reduced pressure, and the extract was combined and weighed to obtain an ointment rate of 20.10-23.20 g/kg, and the extract was stored at 4C for spare use. With 18-19% HCl solution ultrasonic dissolution of CaoWu extract, filtration of the aqueous layer to remove the oil in the CaoWu, with about 40% NaOH solution precipitation of the aqueous layer, a large number of yellow-white precipitate appeared, cooling, filtration of the precipitate, precipitate freeze-drying, weighed yellow-white precipitate of 7.2-7.9g/kg, 4 to save standby.

2) Separation of aconite protoalkali: Take part of the yellow-white precipitate of NaOH base and separate it with 200-300 mesh silica gel, use n-hexane/ethyl acetate as the mobile phase and rinse the silica gel column. The column separation was stopped by tracking aconitine with thin-layer chromatography until the point of aconitine disappeared. The resulting crude aconitine was recrystallized by dichloromethane to obtain the pure aconitine.

NF-κB

[1] KENTARO WADA  Youkichi O  Makoto Nihira. Effects of chronic administrations of aconitine on body weight and rectal temperature in mice[J]. Journal of ethnopharmacology, 2006, 105 1: Pages 89-94. DOI: 10.1016/j.jep.2005.10.007
[2] XIANG-ZHOU ZENG. Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression[J]. Acta Pharmacologica Sinica, 2015, 37 2: 255-263. DOI: 10.1038/aps.2015.85
[3] TENG-FEI LI Y W Nian Gong. Ester Hydrolysis Differentially Reduces Aconitine-Induced Anti-hypersensitivity and Acute Neurotoxicity: Involvement of Spinal Microglial Dynorphin Expression and Implications for Aconitum Processing[J]. Frontiers in Pharmacology, 2016, 7 1. DOI: 10.3389/fphar.2016.00367