A new denudatine-type C sub(20)-diterpenoid alkaloid, pubesine (1), along with seven known diterpenoid alkaloids, altaconitine (2), 14-benzoylaconine (3), spicatine A (4), ...14-benzoylaconine-8-palmitate (5), 14-O-acetylsenbusine A (6), senbusine A (7) and 14-acetylneoline (8) were isolated from the whole plant of Aconitum soongaricum var. pubescens. Their structures were elucidated by means of extensive spectroscopic analyses (NMR and HR-ESI-MS) and comparison with data reported in the literature. All compounds were evaluated for their cytotoxicity against H460, MCF-7 and Hep G2 human cancer cell lines.
Influence of plant growth regulators on indirect regeneration and secondary metabolite production in Aconitum violaceum Jacq. was evaluated. Among the different plant growth regulators studied, 2.5 ...mu M 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.25 mu M kinetin (Kn) promoted the highest frequency of callus production for indirect regeneration. 6-Benzyl aninopurine (BAP) was more effective in improving shoot regeneration and secondary metabolite production compared to thidiazuron (TDZ). The highest frequency of regeneration (61.8%) was obtained when calli were transferred to Murashige and Skoog medium supplemented with 1 mu M BAP and 0.5 mu M alpha --naphthalene acetic acid (NAA) and was more than two-times higher when compared to the treatments with cytokinin only. Supplementation with low NAA concentrations resulted reduction in in vitro secondary metabolite production in most cases, when compared to treatments with cytokinin only. Moreover, differences in cytokinin concentrations significantly affected secondary metabolite production in some cases. The current findings highlighted the differential effects of auxin-cytokinin interactions on indirect shoot regeneration and the production of secondary metabolites in A. violaceum.
Aconitum heterophyllum is a plant that has very important medicinal value. Lots of phytochemical constituents (metabolites) are extracted from this plant, especially diterpene alkaloids which are the ...main compounds having pharmacological activities such as analgesic and anti-inflammatory. Study of the structures of these compounds was done by the technique of nuclear magnetic resonance.
In this study, we conducted an assembly and analysis of the organelle genomes of Aconitum carmichaelii. Our investigation encompassed the examination of organelle genome structures, gene transfer ...events, and the environmental selection pressures affecting A. carmichaelii. The results revealed distinct evolutionary patterns in the organelle genomes of A. carmichaelii. Especially, the plastome exhibited a more conserved structure but a higher nucleotide substitution rate (NSR), while the mitogenome displayed a more complex structure with a slower NSR. Through homology analysis, we identified several instances of unidirectional protein-coding genes (PCGs) transferring from the plastome to the mitogenome. However, we did not observe any events which genes moved from the mitogenome to the plastome. Additionally, we observed multiple transposable element (TE) fragments in the organelle genomes, with both organelles showing different preferences for the type of nuclear TE insertion. Divergence time estimation suggested that rapid differentiation occurred in Aconitum species approximately 7.96 million years ago (Mya). This divergence might be associated with the reduction in CO
levels and the significant uplift of the Qinghai-Tibet Plateau (QTP) during the late Miocene. Selection pressure analysis indicated that the dN/dS values of both organelles were less than 1, suggested that organelle PCGs were subject to purification selection. However, we did not detect any positively selected genes (PSGs) in Subg. Aconitum and Subg. Lycoctonum. This observation further supports the idea that stronger negative selection pressure on organelle genes in Aconitum results in a more conserved amino acid sequence. In conclusion, this study contributes to a deeper understanding of organelle evolution in Aconitum species and provides a foundation for future research on the genetic mechanisms underlying the structure and function of the Aconitum plastome and mitogenome.
Blocking specific K super(+) channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and ...electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K super(+) channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K super(+), Na super(+) and Ca super(2) super(+) currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K super(+) channel. External application of talatisamine reversibly inhibited the delayed rectifier K super(+) current (I sub(K)) with an IC sub(5) sub(0) value of 146.0+/-5.8 mu M in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na super(+) and Ca super(2) super(+) currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of I sub(K) and its recovery from inactivation, suggesting that talatisamine had no allosteric action on I sub(K) channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific I sub(K) channel blocker from Aconitum alkaloids. It has been argued that suppressing K super(+) efflux by blocking I sub(K) channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.
Aconitum kusnezoffii Reichb. has been used as traditional Chinese medicine over the last 2500 years, but its polysaccharides have been paid little attention by now. In the present study, a hot alkali ...extracted polysaccharide (AKP) from A. kusnezoffii Reichb. was characterized to be an a-(1 --> 3),(1 --> 4)-d-glucan with Mw 1.4 x 10 super(5) Da, of which (1 --> 3)-linked and (1 --> 4)-linked a-Glcp residues were in a ratio of 1:7. In vitro antioxidant testing indicated that AKP had significant ferrous ion-chelating ability, reducing power and scavenging effects on DPPH radical, hydroxyl radical, superoxide anion, H sub(2)O sub(2) and self-oxidation of 1,2,3-phentriol, suggesting that it should be explored as a novel natural antioxidant.
is an important medicinal herb used widely in China, Japan, India, Korea, and other Asian countries. While extensive research on the characterization of metabolic extracts of
has shown accumulation ...of numerous bioactive metabolites including aconitine and aconitine-type diterpene alkaloids, its biosynthetic pathway remains largely unknown. Biosynthesis of these secondary metabolites is tightly controlled and mostly occurs in a tissue-specific manner; therefore, transcriptome analysis across multiple tissues is an attractive method to identify the molecular components involved for further functional characterization. In order to understand the biosynthesis of secondary metabolites, Illumina-based deep transcriptome profiling and analysis was performed for four tissues (flower, bud, leaf, and root) of
, resulting in 5.5 Gbps clean RNA-seq reads assembled into 128,183 unigenes. Unigenes annotated as possible rate-determining steps of an aconitine-type biosynthetic pathway were highly expressed in the root, in accordance with previous reports describing the root as the accumulation site for these metabolites. We also identified 21 unigenes annotated as cytochrome P450s and highly expressed in roots, which represent candidate unigenes involved in the diversification of secondary metabolites. Comparative transcriptome analysis of
with
identified 20,232 orthogroups, representing 30,633 unigenes of
, gene ontology enrichment analysis of which revealed essential biological process together with a secondary metabolic process to be highly enriched. Unigenes identified in this study are strong candidates for aconitine-type diterpene alkaloid biosynthesis, and will serve as useful resources for further validation studies.
Aconitum species are well-known for their medicinal value and high lethal toxicity in many Asian countries, notably China, India and Japan. The tubers are only used after processing in Traditional ...Chinese Medicine (TCM). They can be used safely and effectively with the methods of decoction, rational compatibility, and correct processing based on traditional experiences and new technologies. However, high toxicological risks still remain due to improper preparation and usage in China and other countries. Therefore, there is a need to clarify the methods of processing and compatibility to ensure their effectiveness and minimize the potential risks.
The aim of this paper is to provide a review of traditional and current methods used to potentially reduce toxicity of Aconitum roots in TCM.
The use of Aconitum has been investigated and the methods of processing and compatibility throughout history, including recent research, have been reviewed.
Using of the methods of rational preparation, reasonable compatibility, and proper processing based on traditional experiences and new technologies, can enable Aconitum to be used safely and effectively.
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Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute ...toxicity. Aconitum alkaloids are responsible for its pharmacological activity and toxicity. Although a large number of studies on Fuzi have been reported, no comprehensive review on its pharmacokinetics has yet been published.
This paper seeks to present a comprehensive review regarding the phytochemistry, pharmacokinetic features and toxicity of Fuzi. The regulation of drug-metabolizing enzymes (DMEs) and efflux transporters (ETs) by Fuzi is also concluded. Additionally, the use of Fuzi as a personalized medicine based on the bioavailability barrier (BB), which mainly comprises DMEs and ETs, is discussed.
All available information on Fuzi was collected by searching for key words in PubMed, ScienceDirect, CNKI, Google Scholar, Baidu Scholar, and Web of Science.
Aconitum alkaloids, which mainly include diester-diterpene alkaloids (DDAs), monoester-diterpene alkaloids (MDAs) and unesterified-diterpene alkaloids (UDAs), could be detected after Fuzi ingestion in vivo. The Aconitum alkaloids are rapidly absorbed in the intestine and extensively distributed in the body. DMEs, especially CYP3A4/5, are responsible for various types of metabolic reactions of the Aconitum alkaloids. ETs, including P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), are involved in the efflux of the DDAs and MDAs. The kidney is the most important organ involved in the excretion of the Aconitum alkaloids. DDAs are the main toxic compounds present in Fuzi, and their acute toxicity is mainly due to their effects on the voltage-dependent sodium channels. Furthermore, Fuzi can substantially regulate DMEs and ETs.
The toxicity of DDAs is acute. However, further investigations are necessary to determine the exact toxicological mechanisms. The significant impact of Fuzi on DMEs and ETs suggests that the co-administration of Fuzi with drugs that are substrates of DMEs and/or ETs may cause herb-drug interactions (HDIs). The BB network controlled exposure to the Aconitum alkaloids in vivo. Polymorphisms of DMEs and ETs in different individuals contribute to the differences in the efficacy and toxicity of Fuzi ingestion. In the future, the use of Fuzi as personalized medicine based on the BB network is necessary and practical to achieve ideal therapeutic efficacy with minimal toxicity.
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Combinatorial contribution of the MVA/MEP pathways genes was found to be correlated to high aconites content in A. heterophyllum providing insights for its genetic improvement. Display omitted
...•Comparative genomics utilized to clone and sequence 15 genes of MVA/MEP pathways in A. heterophyllum.•Expression analysis of all 15 genes in relation to aconites content carried out by qPCR.•Correlation among pathways genes and alkaloids content proved by PCA analysis.•First report on high aconites content accessions.•First attempt to understand aconites biosynthesis and accumulation in A. heterophyllum.
Aconitum heterophyllum Wall, popularly known as Atis or Patis, is an important medicinal herb of North-Western and Eastern Himalayas. No information exists on molecular aspects of aconites biosynthesis, including atisine- the major chemical constituent of A. heterophyllum. Atisine content ranged from 0.14% to 0.37% and total alkaloids (aconites) from 0.20% to 2.49% among 14 accessions of A. heterophyllum. Two accessions contained the highest atisine content with 0.30% and 0.37% as well as the highest alkaloids content with 2.22% and 2.49%, respectively. No atisine was detected in leaves and shoots of A. heterophyllum, thereby, suggesting that the biosynthesis and accumulation of aconite alkaloids occur mainly in roots. Quantitative expression analysis of 15 genes of MVA/MEP pathways in roots versus shoots, differing for atisine content (0–2.2 folds) showed 11–100 folds increase in transcript amounts of 4 genes of MVA pathway; HMGS, HMGR, PMK, IPPI, and 4 genes of MEP pathway; DXPS, ISPD, HDS, GDPS, respectively. The overall expression of 8 genes decreased to 5–12 folds after comparative expression analysis between roots of high (0.37%) versus low (0.14%) atisine content accessions, but their relative transcript amounts remained higher in high content accessions, thereby implying their role in atisine biosynthesis and accumulation. PCA analysis revealed a positive correlation between MVA/MEP pathways genes and alkaloids content. The current study provides first report wherein partial sequences of 15 genes of MVA/MEP pathways have been cloned and studied for their possible role in aconites biosynthesis. The outcome of study has potential applications in the genetic improvement of A. heterophyllum.
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