As a folk medicine, Aconitum sinomontanum Nakai (Ranunculaceae) a perennial herbaceous flowering plant, is a widely used traditional Chinese medicine. Its rhizomes and roots are known as 'Gaowutou' in China, and it has been traditionally used for the treatment of rheumatoid arthritis, painful swelling of joints, bruises and injuries and has been known to grow well in regions of high altitude such as Gansu, Tibet etc. THE AIM OF THE REVIEW: This systematic review the comprehensive knowledge of the A. sinomontanum, including its traditional processing and uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and its use in clinical settings to emphasize the benefits of this species. We also discuss expectations for prospective research and implementation of this herb. This work lays a solid foundation for further development of A. sinomontanum.

Information on the studies of A. sinomontanum was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters dissertation.

As a member of the Ranunculaceae family, A. sinomontanum possesses its up-and-coming biological characteristics. It is widely reported for treating rheumatoid arthritis, painful swelling of joints, bruises and injuries. Currently, over 71 phytochemical ingredients have been obtained and identified from different parts of A. sinomontanum. Among them, alkaloids, flavonoids, steroids, glycosides are the major bioactive constituents. Activities such as antinociceptive, anti-inflammatory, antitumor, antiarrhythmic, local anesthetic, antipyretic, antimicrobial, insecticidal and others have been corroborated in vivo and in vitro. These properties are attributed to different alkaloids. In addition, many of the active ingredients, such as lappaconitine, ranaconitine and total alkaloids have been used as quality markers.

This work contributes to update the ethnopharmacological uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and clinical settings information for A. sinomontanum, which provide basic information to help better understand the pharmacological and toxicological activities of A. sinomontanum in human. However, further in-depth studies are needed to determine the medical uses of this herb and its chemical constituents, pharmacological activities, clinical applications and toxicology.

The diterpenoid alkaloids are a family of extremely important natural products that have long been a research hotspot due to their myriad of intricate structures and diverse biological properties. This chapter systematically summarizes the past 11 years (2009-2019) of studies on the diterpenoid alkaloids, including the "so-called" atypical ones, covering the classification and biogenetic relationships, phytochemistry together with 444 new alkaloids covering 32 novel skeletons and the corrected structures, chemical reactions including conversion toward toxoids, synthetic studies, as well as biological activities. It should be noted that the synthetic studies, especially the total syntheses of various diterpenoid alkaloids, are for the first time reviewed in this treatise. This chapter, in combination with our four previous reviews in volumes 42, 59, 67, and 69, will present to the readers a more completed and updated profile of the diterpenoid alkaloids.

This review systematically summarizes the C18-diterpenoid alkaloid (DA) compositions isolated from the genera Aconitum and Delphinium in the Delphineae tribe (Ranunculaceae). A total of 117 distinct C18-DA components have been reported, including 58 lappaconitine-type DAs, 54 ranaconitine-type DAs, and five rearranged-type DAs. These components mainly originated from plants from the subgenus Lycoctonum in the genus Aconitum or less frequently from plants within the genus Delphinium. Natural C18-DAs have exhibited a wide range of bioactivities, including analgesic, antiarrhythmic, anti-inflammatory, anti-tumor, and insecticidal activities, which are closely related to their chemical structures. The high chemical and biological diversities among the reported C18-DA constituents in Delphineae plants indicated their potential as a vast resource for drug discovery. Additionally, the Delphineae plant C18-DAs exhibited chemotaxonomic values and showed a high regularity of distribution at different taxonomic levels; therefore, the Delphineae plant C18-DAs can serve as good chemical molecular markers in the taxonomic treatment of plants within this tribe, especially in the infrageneric division.

A phytochemical study led to the isolation of 25 diterpenoid alkaloids from Aconitum sinomontanum, of which six were described for the first time. Among them compounds 1-3 are anhydrolycoctonine derivatives, rare rearranged aconitine-type C₁₉-diterpenoid alkaloids. To our best knowledge, less than ten of this type of alkaloids were isolated just from the genus Aconitum. The structures of these unreported compounds were elucidated by extensive analysis of NMR spectroscopic data and X-ray diffraction. The biological activities of compounds 1-3, 5-9, and 12-25 were evaluated. Among the tested compounds, compounds 2 and 17 showed potent inhibitory effect on the capsaicin (selective TRPV1 agonist) mediated activation of transient receptor potential vanilloid 1 (TRPV1) channels expressed in HEK-293 cells with inhibition rate of 31.78% and 30.94% at the concentration of 10 μM. Compounds 1-3, 5-9, 13, and 18-25 exhibited weak cytotoxic activity against human tumor cell lines NCI-H226 and MDA-MB-231 with inhibition rate over 10% at the concentration of 10 μM. Compound 16 showed most inhibitory effect on the expression of Nrf2 (NF-E2-related factor-2)-regulated gene with inhibition rate of 25% at the concentration of 20 μM.

Covering: 2009 to 2018. Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, are a diverse class of compounds having complex structural features with many stereocenters. The important pharmacological activities and structural complexity of the diterpenoid alkaloids have long interested scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. Since 2009, 373 diterpenoid alkaloids, assigned to 46 skeletons, have been isolated and identified from plants mostly in the Ranunculaceae family. The names, classes, molecular weight, molecular formula, NMR data, and plant sources of these diterpene alkaloids are collated here. This review will be a detailed update of the naturally occurring diterpene alkaloids reported from the plant kingdom from 2009-2018, providing an in-depth discussion of their diversity, biological activities, pharmacokinetics, toxicity, application, evolution, and biosynthesis.

Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the Aconitum, Delphinium, Consolida genera. Corals, Xenia, Okinawan/Clavularia, Alcyonacea (soft corals) and marine sponges are rich sources of diterpenoids, despite the difficulty to access them and the lack of availability. Researchers have long been concerned with the potential beneficial or harmful effects of diterpenoid alkaloids due to their structural complexity, which accounts for their use as pharmaceuticals as well as their lousy reputation as toxic substances. Compounds belonging to this unique and fascinating family of natural products exhibit a broad spectrum of biological activities. Some of these compounds are on the list of clinical drugs, while others act as incredibly potent neurotoxins. Despite numerous attempts to prepare synthetic products, this review only introduces the natural diterpenoid alkaloids, describing 'compounds' structures and classifications and their toxicity and bioactivity. The purpose of the review is to highlight some existing relationships between the presence of substituents in the structure of such molecules and their recognised bioactivity.

Extensive phytochemical investigation from the roots of Aconitum kirinense Nakai led to the identification of fifteen new compounds, including four ranaconitine type C₁₈-diterpenoid alkaloids (kirisines A-D, 1-4), one lappaconitine type C₁₈-diterpenoid alkaloid (kirisine E, 5), seven denudatine type C₂₀-diterpenoid alkaloids (kirisines F-L, 6-12), and three napelline type C₂₀-diterpenoid alkaloids (kirisines M-O, 13-15), together with 25 known ones. Their structures were elucidated by extensive spectroscopic analyses. Among them, compounds 1 and 2 are rare diterpenoid alkaloid with 9,14-methylenedioxy group, and the latter also has a rare chloro-substituent. The diterpenoid alkaloids isolated were C₁₈, C₁₉ and C₂₀-category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The isolated compounds were tested for neuroprotective activity and acetylcholinesterase inhibitory activity. Compounds 7, 18, 30 and 40 which exhibited moderate activity at 80 μM against acetylcholinesterase.