C18-diterpenoid alkaloids in tribe Delphineae (Ranunculaceae): phytochemistry, chemotaxonomy, and bioactivities

This review systematically summarizes the C18-diterpenoid alkaloid (DA) compositions isolated from the genera Aconitum and Delphinium in the Delphineae tribe (Ranunculaceae).

Effect of diterpene alkaloids on lipid peroxidation in mitochondria

In this article, the antioxidant activity of some alkaloids lipid peroxidation (LPO) in rat liver mitochondria has been studied. It has been established that diterpenoid alkaloids: 1-О-benzoylnapelline, napelline and songorine have a protective effect on mitochondria, reducing the damaging effect of Fe2+/ascorbate and the release of malondialdehyde (MDA) into the secondary products of peroxidation. The effect of alkaloids napelline, 1-O-benzoylnapelline and songorine on the processes of MDA formation in rat liver mitochondria in vitro has been studied.Where in at 200 мM concentrations, 1-О-benzoylnapelline inhibited the formation of MDA by 95 %, and the alkaloids napelline and songorine at this concentration inhibited the formation of MDA by 54 and 44 %. From the data obtained, it can be shown that 1-О-benzoylnapelline strongly inhibits the formation of MDA compared to songorine and napelline.

Attenuation and Structural Transformation of Crassicauline A During Sand Frying Process and Antiarrhythmic Effects of its Transformed Products

To ensure safety and efficacy, most Aconitum herbs should be processed before clinical application. The processing methods include boiling, steaming, and sand frying. Among these methods, the transformation pathways of diterpenoid alkaloids in the process of sand frying are more complicated. Therefore, crassicauline A, a natural product with two ester bonds, was chosen as the experimental object. Consequently, a known alkaloid, together with three new alkaloids, was derived from crassicauline A. Meanwhile, the cardiotoxicity of converted products was reduced compared with their parent compound. Interestingly, some diterpenoid alkaloids have similar structures but opposite effects, such as arrhythmia and antiarrhythmic. Considering the converted products are structural analogues of crassicauline A, herein, the antiarrhythmic activity of the transformed products was further investigated. In a rat aconitine-induced arrhythmia assay, the three transformed products, which could dose-dependently delay the ventricular premature beat (VPB) incubation period, reduce the incidence of ventricular tachycardia (VT), combined with the increasing arrhythmia inhibition rate, exhibited prominent antiarrhythmic activities. Our experiments speculated that there might be at least two transformation pathways of crassicauline A during sand frying. The structure-activity data established in this paper constructs the critical pharmacophore of diterpenoid alkaloids as antiarrhythmic agents, which could be helpful in searching for the potential drugs that are equal or more active and with lower toxicity, than currently clinical used antiarrhythmic drugs.

Attenuated Structural Transformation of Aconitine during Sand Frying Process and Antiarrhythmic Effect of Its Converted Products

The transformation pathways of diterpenoid alkaloids have been clarified in the boiling and steaming process. Aconitine, a famous diterpenoid alkaloid, is successively transformed into benzoylaconine and aconine during the processes of boiling and steaming, but the transformation pathway remains to be determined in the sand frying process. The present study aims at investigating the transformation pathways of aconitine in the process of sand frying, as well as assessing the cardiotoxicity and antiarrhythmic activity of aconitine and its converted products. The parameters of temperature and time for the structural transformation of aconitine were confirmed by HPLC. The converted products were further separated and identified by column chromatography, NMR, and HR-ESI-MS. Furthermore, by observing the lead II electrocardiogram (ECG) changes in rats under an equivalent dose, the cardiotoxicity of aconitine and its converted products were compared. Ultimately, the antiarrhythmic effect of the converted products was investigated by employing the model of aconitine-induced arrhythmia. Consequently, the structure of aconitine was converted when processed at 120°C–200°C for 1–40 min. Two diterpenoid alkaloids, a pair of epimers, namely, pyroaconitine and 16-epi-pyroaconitine, were further isolated from processed aconitine. 0.03 mg/kg aconitine induced arrhythmias in normal rats, while the converted products did not exhibit arrhythmias under an equal dose. In the antiarrhythmic assay, 16-epi-pyroaconitine could dose-dependently delay the onset time of VPB, reduce the incidence of VT, and increase the arrhythmia inhibition rate, demonstrating comparatively strong antiarrhythmic activity. Conclusively, compared with the prototype compound aconitine, the converted products exhibited lower cardiotoxicity. Further investigations on the cardiotoxicity indicated that pyroaconitine with β configuration had a stronger cardiotoxicity than 16-epi-pyroaconitine with α configuration. Furthermore, 16-epi-pyroaconitine could antagonize the arrhythmogenic effect caused by the prototype compound aconitine; the antiarrhythmic effect of 16-epi-pyroaconitine was stronger than lidocaine and propafenone, which had the potential to be developed as antiarrhythmic drugs.

Chemistry, biological activities and toxic effects of alkaloidal constituents of genus Delphinium - A mini review

The genus Delphinium is one of the essential members of the family Ranunculaceae. These species grow wild in North America, Europe, and Asia. They have demonstrated antioxidant, antimicrobial, and cytotoxic activities. Diterpenoid alkaloids are their main constituents and seem to be responsible for medicinal and toxic properties. The primary purpose of this paper is to review the therapeutic benefits of Delphinium species, chemical composition, and its medicinal uses, in addition to the reported toxic effects of these plants influencing different animals and humans.