Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

Study on multi-index components of Tibetan medicine Bangna of Aconitum genus according to fingerprints and chemometrics / 中草药

Objective: To establish the chemical fingerprint and multi-index components determination of Tibetan medicine Bangna of Aconitum genus, and provide references for the formulation of quality standards of multi-base original medicinal materials and clinically safe medication. Methods: HPLC fingerprint of Bangna was established and evaluated by the similarity evaluation system of TCM. In addition, the content of the seven components of Bangna from 30 batches and the difference of chemical information between the two species of Bangna was investigated by principal component analysis and orthogonal partial least squares discrimination analysis (OPLS-DA) respectively. Results: A total of 17 common peaks were identified in the fingerprint that was established by the determination of 30 batches of Bangna, and seven components of which were identified with 12-epi-napelline, songorine, benzoylmesaconitine, benzoylaconine, mesaconitine, aconitine, 3-acetylaconitine. Based on similarity results, the fingerprint had good consistency between the same origin and minor diversity between the different sources. The results of principal component analysis and OPLS-DA showed that there were some differences in the content of seven components between the two species. Based on the results of OPLS-DA and t test, it could be determined that the contents of 12-epi-napelline and aconitine of Aconitum flavum were significantly higher than those in Aconitum pendulum (P < 0.01). Conclusion: The fingerprint and multi-component quantitative analysis methods were used for the quality and clinically safe medication control of Bangna in this paper is simple, easy to operate, and informative. Moreover, it is necessary to establish and improve the limit determination of diester alkaloids.

Development of natural products as drugs acting on central nervous system

We have recenty studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

Effects of lappaconitine on the toxicity and analgesic activity of 3-acetylaconitine in their combination / 中国药理学通报

Lappaconitine (LA) 0. 5 mg? kg-1had significant antagonistic action on the ar-rythmia induced by 3-acetylaconitine ( AA ) 0.07 mg?kg-1in rat. When LA and AA were used in combination (7:1) in mice, the analgesic activity of AA was not influenced marked-ly by LA but the LD50 of AA was increased by 50% ,therefore the therapeutic index of AA was increased and the margin of safety was widened.