An overview of the research progress on Aconitum carmichaelii Debx.:active compounds, pharmacology, toxicity, detoxification, and applications

Ethnopharmacological relevance: Aconitum carmichaelii Debx. is the most widely distributed species of Aconitum plants in China and has a long history of medicinal use. Because of its toxicity, A. carmichaelii is classified as lower class in the Shennong Bencao Jing (Shennong's Classic of Materia Medica). According to the theory of Chinese medicine, the roots can be used to revive yang for resuscitation, dispel wind, remove dampness, and relieve pain. Aims of the review: This review focuses on summarizing the latest reports on the components, pharmacology, toxicity, detoxification mechanism and application of A. carmichaelii. It aims to provide ideas for in-depth research on activity mechanism of A. carmichaelii and expanding the value of exploitation and utilization. Materials and methods Information was collected from the following online scientific databases: PubMed, Web of Science, Wiley Online Library, SciFinder, Scopus, PubChem, China National Knowledge Internet (CNKI), etc. Additional data were obtained from other Chinese medicine books. Results: In this review, 224 compounds were categorized and new compounds discovered in the last five years were highlighted. The main components of A. carmichaelii are C-19-diterpene alkaloids(C-19-DAs), among which diester-type aconitine is the most toxic and also the main active ingredient, while monoester diterpene alkaloids (MDAs) and aminol diterpene alkaloids (ADAs) are greatly toxicity reduced due to the loss of ester bond. Heating and compatibility are the means to increase the efficiency and reduce the toxicity of A. carmichaelii. In addition, it also contains abundant C-20-diterpene alkaloids (C-20-DAs). Like C-19-DAs, these compounds also have cardiotonic, anticancer, anti-inflammatory and analgesic pharmacological effects, but their toxicity is weaker. The above-ground part contains not only a variety of MDAs and ADAs, but also contains abundant non-diterpenoid alkaloids and active polysaccharides. In addition to pharmacological effects, we further summarized the mechanisms of cardiotoxicity, neurotoxicity and other toxicity of A. carmichaelii. What's more, the application prospects are also discussed. Polysaccharides and diterpenoid alkaloids in A. carmichaelii and related traditional prescriptions have great promising prospects for the development of new drugs. Conclusion: A. carmichaelii has rich alkaloids and polysaccharides, but the new compounds discovered in recent years are only in the activity screening stage. The toxic differences between C-19- and C-20- DAs and the dose that affect toxicity of A. carmichaelii are still not clear. The non-traditional medicinal parts, such as stems and leaves, show great potential for development and utilization. More extensive and in-depth exploration of low-toxic active compounds, as well as the mechanism of efficacy-enhancement and toxicity-attenuation, will help A. carmichaelii to be better and safer used for clinical.