Aconitum Species Research Articles

Aconitine in Synergistic, Additive and Antagonistic Approaches

Aconitine is a highly poisonous C19-diterpenoid alkaloid identified and isolated from the species of the genus Aconitum. Aconitine is indicated in the treatment of cardiovascular diseases (CVDs) and, due to its neurotoxic effects, is a very effective drug in pain release. A total of 101 relevant scientific papers were manually searched on the Web of Science, Scopus, Science Direct, Google Scholar, PubMed and Dovepress databases and in the books available in the library of the Department of Natural Sciences, the National University of Science and Technology POLITEHNICA Bucharest, Pitesti University Centre, Romania. In combination treatments, aconitine shows antiarrhythmic and anti-inflammatory activity, a synergistic antiproliferative effect and decreased reactive oxygen species (ROS) generation, an improved biodistribution and bioavailability. Additionally, the entrapment of aconitine in engineered nanoparticles represents a promising method for reducing the toxicity of this alkaloid. This review provides, for the first time, a comprehensive picture of the knowledge and research on the synergistic, additive and antagonistic effects of aconitine in combination treatments applied in vivo or in vitro. The summarized studies represent important clues in addressing the multitude of knowledge, which can find their utility in practical and clinical applications.

Complete chloroplast genomes of eight Delphinium taxa (Ranunculaceae) endemic to Xinjiang, China: insights into genome structure, comparative analysis, and phylogenetic relationships

BackgroundDelphinium L. represents a taxonomically intricate genus of significant phylogenetic and economic importance in Ranunculaceae. Despite the existence of few chloroplast genome datasets, a comprehensive understanding of genome structures and selective pressures within the genus remains unknown. Furthermore, several taxa in this genus are exclusively found in Xinjiang, China, a region renowned for its distribution and diversity of Chinese and Central Asian Delphinium species. Therefore, investigating the features of chloroplast genomes in this area will provide valuable insights into the evolutionary processes and phylogenetic relationships of the genus.ResultsIn this study, the eight newly completed chloroplast genomes are examined, ranging in length from 153,979 bp to 154,284 bp. Alongside these, analysing six previously reported taxa re-annotated in Delphinium, 111 unique genes are identified across all samples. Genome structure, distributions of simple sequence repeats and short dispersed repeats, as well as gene content are similar among these Delphinium taxa. Nine hypervariable intergenic spacers and protein coding regions, including ndhF-trnL(TAG), rpl16-intron, rpl33, rps15, rps18, trnK(TTT)-trnQ(TTG), trnP(TGG)-psaJ, trnT(GGT)-psbD and ycf1, are identified among 13 perennial Delphinium. Selective pressure and codon usage bias of all the plastid genes are performed within 14 Delphinium taxa. Phylogenetic analysis based on 14 Delphinium plastomes, alongside two Aconitum (Ranunculaceae) species serving as outgroup taxa, reveals the monophyletic nature of Delphinium. Our findings further discern Delphinium into two distinct clades: perennial species (clade I) and annual species (clade II). In addition, compared with the nrDNA ITS topology, cytological data and morphological characters, D. mollifolium and D. maackianum showed potential involvement in hybridization or polyploidization processes. Excluding these two species, the perennial Delphinium (clade I) exhibits a stronger consistency with the morphology-based system that utilized seed morphology.ConclusionThis study represents the first comprehensive analysis of plastomic variations among Delphinium taxa, based on the examination of 14 complete plastomes. The chloroplast genome structure of Delphinium is similar to other angiosperms and possesses the typical quadripartite structure with the conserved genome arrangement and gene features. In addition, the variation of non-coding regions is larger than coding regions of the chloroplast genome. Through DNA sequence divergence across Delphinium plastomes and subsequent phylogenomic analyses ndhF-trnL(TAG) and ycf1 are identified as promising molecular markers. These highly variable loci held significant potential for future phylogenetic and phylogeographic studies on Delphinium. Our phylogenomic analyses based on the whole plastomes, concatenation of 132 unique intergenic spacer regions, concatenation of 77 unique protein-coding genes and nrDNA ITS, all support the monophyly of Delphinium and perennial taxa clusters together into one clade within this genus. These findings provide crucial data for systematic, phylogenomic and evolutionary research in the genus for future studies.

Role of P-glycoprotein in Regulating the Efficacy, Toxicity and Pharmacokinetics of Yunaconitine.

Yunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear. The objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC. The efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice. The presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco- 2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice. YAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.

‘Queen of Poisons’ Aconitum with special reference to Indian Aconite - Vatsanabha

Aconitum, the "Queen of Poisons" commonly known as Monkshood or Wolf’s bane, is a genus of perennial plants belonging to the family Ranunculaceae. In Ayurveda also few species of Aconitum are used for its therapeutic actions and the most potent of them is Aconitum Ferox, also known as Indian aconite or Vatsanabha, and it has the ability to function as both the ultimate poison and an elixir. In Ayurveda, Vatsanabha is considered as Mahavisha included among Sthavara Visha by Acharya Charaka, and in Kanda Visha by Acharya Susrutha. Aconitum Ferox is a highly toxic with the estimated fatal dose of 1g of root powder with a fatal period of 6 hours which contains a potent cardiotoxin and neurotoxin known as Aconitine. Ingesting even a small amount of the plant can result in severe symptoms and even death. As a result of the high toxicity of Vatsanabha, prior to any therapeutic use, the roots should under gone proper Sodhana process. Rasayana (rejuvenating), Deepana (improves digestion), Balavardhana (improves strength) Agnimandyahara (relieves indigestion) Pleehodara (useful in splenomegaly), Vataraktahara (useful against gout) Shwasahara (useful respiratory diseases), Kasahara (relieves cough), Gudamayahara (useful in ano-rectal disorders) etc. are just a few of the therapeutic indications of Vatsanabha that have been used successfully to treat a range of medical conditions. Recent Researches have shown that Vatsanabha contains several biologically active compounds that may have numerous potential therapeutic properties. The pharmacological potential of Aconitum Ferox still justifies vast research possibilities.

Comparative analysis of the organelle genomes of Aconitum carmichaelii revealed structural and sequence differences and phylogenetic relationships

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 CO2 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.

Anti-rheumatic potential vis-à-vis aconitine and hypaconitine content analysis in different Aconitum spp. from Sikkim Himalayas (India).

Aconitum spp. are important medicinal plants mentioned in Ayurveda as Ativisa or Vatsanabha. The present study aims to evaluate anti-rheumatic potential in seven Aconitum species and correlation with aconitine and hypaconitine content. Anti-rheumatic potential was analyzed through in vitro xanthine oxidase inhibition, anti-inflammatory and ROS scavenging assays; and quantification of aconitine and hypaconitine with RP-HPLC method validated as per ICH guidelines. The findings reveal that A. palmatum possessed the most promising response (IC50 =12.68±0.15 μg/ml) followed by A. ferox (IC50 =12.912±1.87 μg/ml) for xanthin oxidase inhibition. We observed a wide variation in aconitine and hypaconitine content ranging from 0.018 %-1.37 % and 0.0051 %-0.077 % respectively on dry weight basis. Aconitine and hypaconitine showed moderate positive correlation (r=0.68 and 0.59 respectively) with anti-rheumatic potential. The study identifies potential alternative species of Aconitum that can help in sustainable availability of quality raw material.

Exploring DNA barcode for accurate identification of threatened Aconitum L. species from Western Himalaya.

Aconitum species, belonging to Ranunculaceae, have high medicinal importance but due to their overexploitation come under IUCN (International Union for Conservation of Nature) red list. The precise identification of the Aconitum species is equally important because they are used in herbal formulations. The present study aimed to develop an efficient DNA barcode system for the authentic identification of Aconitum species. A set of 92 barcode gene sequences (including 12 developed during the present study and 80 retrieved from NCBI) of 5 Aconitum species (A. heterophyllum, A. vialoceum, A. japonicum, A. napellus, and A. stapfianum) were analyzed using three methods (tree-based, distance-based, and similarity-based) for species discrimination. The PWG-distance method was found most effective for species discrimination. The discrimination rate of PWG- distance ranged from 33.3% (rbcL + trnH-psbA) to 100% (ITS, rbcL + ITS, ITS + trnH-psbA and rbcL + ITS + trnH-psbA). Among DNA barcodes and their combinations, the ITS marker had the highest degree of species discrimination (NJ-40%, PWG-100% and BLAST-40%), followed by trnH-psbA (NJ-20%, PWG-60% and BLAST-20%). ITS also had higher barcoding gap as compared to other individual barcodes and their combinations. Further, we also analyzed six Aconitum species (A. balfourii, A. ferox, A. heterophyllum, A. rotundifolium, A. soongaricum and A. violaceum) existing in Western Himalaya. These species were distinguished clearly through tree-based method using the ITS barcode gene with 100% species resolution. ITS showed the best species discrimination power and was used to develop species-specific barcodes for Aconitum species. DNA barcodes developed during the present study can be used to identify Aconitum species.

Analysis of codon usage patterns in 48 Aconitum species

BackgroundThe Aconitum genus is a crucial member of the Ranunculaceae family. There are 350 Aconitum species worldwide, with about 170 species found in China. These species are known for their various pharmacological effects and are commonly used to treat joint pain, cold abdominal pain, and other ailments. Codon usage bias (CUB) analysis contributes to evolutionary relationships and phylogeny. Based on protein-coding sequences (PCGs), we selected 48 species of Aconitum for CUB analysis.ResultsThe results revealed that Aconitum species had less than 50% GC content. Furthermore, the distribution of GC content was irregular and followed a trend of GC1 > GC2 > GC3, indicating a bias towards A/T bases. The relative synonymous codon usage (RSCU) heat map revealed the presence of conservative codons with slight variations within the genus. The effective number of codons (ENC)-Plot and the parity rule 2 (PR2)-bias plot analysis indicate that natural selection is the primary factor influencing the variation in codon usage. As a result, we screened various optimal codons and found that A/T bases were preferred as the last codon. Furthermore, our Maximum Likelihood (ML) analysis based on PCGs among 48 Aconitum species yielded results consistent with those obtained from complete chloroplast (cp.) genome data. This suggests that analyzing mutation in PCGs is an efficient method for demonstrating the phylogeny of species at the genus level.ConclusionsThe CUB analysis of 48 species of Aconitum was mainly influenced by natural selection. This study reveals the CUB pattern of Aconitum and lays the foundation for future genetic modification and phylogenetic analyses.

Distribution of Poisonous Plants in Biomes of the Southern Far East of Russia

Poisonous plants are a collective group of plants of various systematic categories that contain phytotoxins that pose a potential danger to humans and animals. A number of publications both in Russia and abroad are devoted to the problem of patterns of distribution of plants hazardous to human health in connection with environmental factors. This work is a continuation of research into the spread of plants dangerous to humans in Russia. The aim of this work is ecological and geographical analysis of poisonous plants distribution in biomes of the Far East in Russia. Resulted from the research work on the territory of the far-eastern biomes of Russia we revealed 87 the most toxic vascular plant species that belong to 21 plant families. Some of the most poisonous plants of the Russian flora are plants of the genus Aconitum, of the family (Ranunculaceae). About 70 species of this genus grow in Russia, of which 40 are found only in the Far East, since this territory is considered the center of botanical diversity of the genus in question. The cartographical analysis showed that the highest number of poisonous plant species could be found in the south-east regions – in Primorye, the basin of Ussuri river, in the lower and middle course of the river Amur. Based on a map of Russian biomes, optimal habitats for poisonous plants were identified. Maximum number of Aconitum species, as the most poisonous genus of Russian flora, is in the mountain biomes and in the plain forest-steppe biomes in the Amur basin. The types of ecosystems with the maximum abundance and diversity of poisonous plants have been identified. The species richness distribution shows the concentration of poisonous plant species in small mountain biomes and in arid-like biomes. Correlation analysis of relationships between the number of plant species and climatic factors revealed the significant closeness of the correlation with the average annual air temperature (0,66). Maximum correlation closeness appeared to be between number of poisonous plant species per 10 000 km2 and total number of vascular plants per 10 000 km2 (0,81).

Fatal poisoning due to aconite: Autopsy findings and postmortem quantitative analysis.

Aconitum species are commonly used in traditional Chinese medicine, and they have a narrow therapy window due to the possibility of aconitine poisoning. Aconitine poisoning deaths appear infrequently in forensic practice. It is important to collect valuable body samples in time due to the rapid absorption and excretion of aconitine. However, it is unknown whether postmortem samples have value for toxicological analysis if the deceased has experienced long-term treatment before death. Herein, we present a case of a woman who died after 12 days of failed active treatment for aconitine poisoning. Aconitine was detected in the liver tissue. To our knowledge, this is the first case report describing the detection of aconitine in a decedent after long-term active treatment. The findings indicated that the aconitine concentration in liver tissue can be maintained after long-term treatment; this information may therefore serve as a reference in forensic practice.

Functional diversity of diterpene synthases in Aconitum plants

Members of the Aconitum genus within the Ranunculaceae family are known to accumulate a broad array of medicinal and toxic diterpenoid alkaloids (DAs). Historically, ent-copalyl diphosphate (ent-CPP) was considered the sole precursor in DAs biosynthesis. However, the recent discovery of ent-8,13-CPP synthase in A. gymnandrum Maxim., which participates in ent-atiserene biosynthesis, raises the question of whether this gene is conserved throughout the Aconitum genus. In this study, RNA sequencing and PacBio Iso-sequencing were employed to identify diterpene synthases (diTPSs) in four additional Aconitum species with distinct DA compositions. In vitro and in vivo analyses functionally characterized a diverse array of 10 class II and 9 class I diTPSs. In addition to the identification of seven class II diTPSs as ent-CPP synthases, three other synthases generating ent-8,13-CPP, 8,13-CPP, and 8α-hydroxy-CPP were also discovered. Four class I kaurene synthases-like (KSLs) were observed to react with ent-CPP to yield ent-kaurene. Three KSLs not only reacted with ent-CPP but also ent-8,13-CPP to produce ent-atiserene. AsiKSL2-1 was found to react with 8α-hydroxy-CPP to produce Z-abienol and AsiKSL2-2 exhibited no activity with any of the four intermediates. This research delineates the known diterpene biosynthesis pathways in six Aconitum species and explores the highly divergent diterpene synthases within the genus, which are consistent with their phylogeny and may be responsible for the differential distribution of diterpenoid alkaloids in root and aerial parts. These findings contribute valuable insights into the diversification of diterpene biosynthesis and establish a solid foundation for future investigation into DA biosynthetic pathways in Aconitum.

Benzoylaconitine Alleviates Progression of Psoriasis via Suppressing STAT3 Phosphorylation in Keratinocytes.

Psoriasis is a chronic and multifactorial skin disease which is caused by inflammatory infiltrates, keratinocyte hyperproliferation, and accumulation of immune cells. As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-α)/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-α/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.

Neuropharmacological Potential of Diterpenoid Alkaloids.

This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the β-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity.

A review on efforts for improvement in medicinally important chemical constituents inAconitum through biotechnological interventions.

The genus Aconitum belongs to the family Ranunculaceae, is endowed with more than 350 species on the earth. Medicinally important aconitine type of diterpenoid alkaloids are the characteristic compounds in most of the Aconitum species. The present review endeavored the major research carried out in the field of genetic resource characterization, pharmacological properties, phytochemistry, major factors influencing quantity, biosynthetic pathways and processing methods for recovery of active ingredients, variety improvement, propagation methods, and important metabolite production through cell/organ culture of various Aconitum species. More than 450 derivatives of aconitine-type C19 and C20-diterpenoid alkaloids along with a few other non-alkaloidal compounds, such as phenylpropanoids, flavonoids, terpenoids, and fatty acids, have been identified in the genus. A few Aconitum species and theircommon diterpenoid alkaloid compounds are also well characterized for analgesic, inflammatory and cytotoxic properties. However, the different isolated compound needs to be validated for supporting other traditional therapeutical uses of the plant species. Aconitine alkaloids shared common biosynthesis pathway, but their diversification mechanism remains unexplored in the genus. Furthermore, the process needs to be developed on secondary metabolite recovery, mass-scale propagation methods, and agro-technologies for maintaining the quality of products. Many species are losing their existence in nature due to over-exploitation or anthropogenic factors; thus, temporal monitoring of the population status in its habitat, and suitable management programs for ascertaining conservation needs to be developed.

Explore the Problem behind Dispenser Error and Improper Use - “Aconitine” Poisoning in Chinese Medicine

Consumption of Chinese herbal or seeking medical treatment from a Chinese medicine practitioner (CMP) is quite common in Hong Kong. According to the statistics published by the Census and Statistics Department, there are 22% consulted with a healthcare professional, and 15% of these consultations involved Chinese medical practitioners. Generally, Chinese medicines are safe under proper use and supervision. Chinese herbal medicine such as “Aconitine” in the aconitum species dispense error or improper use causing the risk of poisoning. This commentary discusses the context of an incident, dispense error, or improper use of “Aconitine” and its difficulties, or concerns in some case studies, as well as the management for decisions taken and improvement of “Aconitine” dispense error.

Complete chloroplast genome sequences of the medicinal plant Aconitum transsectum (Ranunculaceae): comparative analysis and phylogenetic relationships

BackgroundAconitum transsectum Diels. (Ranunculaceae) is an important medicinal plant that is widely used in traditional Chinese medicine, but its morphological traits make it difficult to recognize from other Aconitum species. No research has sequenced the chloroplast genome of A.transsectum, despite the fact that phylogenetic analysis based on chloroplast genome sequences provides essential evidence for plant classification.ResultsIn this study, the chloroplast (cp) genome of A. transsectum was sequenced, assembled, and annotated. A. transsectum cp genome is a 155,872 bp tetrameric structure including a large single copy (LSC, 87,671 bp) and a small single copy (SSC, 18,891 bp) section, as well as a pair of inverted repeat sequences (IRa and IRb, 25,894 bp each). 131 genes are encoded by the complete cp genome, comprising 86 protein-coding genes, 37 tRNAs, and 8 rRNAs. The most favored codon in the A. transsectum cp genome is AUG, and 46 repeats and 241 SSRs were also identified. The A. transsectum cp genome is similar in size, gene composition, and IR expansion and contraction to the cp genomes of seven Ranunculaceae species. Phylogenetic analysis of cp genomes of 28 plants from the Ranunculaceae family shows that A. transsectum is most closely related to A. vilmorinianum, A. episcopale, and A. forrestii of Subgen. Aconitum.ConclusionsOverall, this study provides complete cp genome resources for A. transsectum that will be beneficial for identifying potential.

High‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry for profiling diterpenoid alkaloids in Aconitum species

AbstractAconitum is known for being rich in toxic diterpenoid alkaloids, and many of them are unilateral medicinal materials constituting traditional Chinese medicine, which have important clinical uses. Previous liquid chromatography‐mass spectrometry studies were mainly focused on a few common species, but lacked in‐depth and detailed research on other species in the same genus, although they have similar or even the same uses. In this study, a comprehensive analysis of the high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry data by semi‐quantitative comparisons of the accurate molecular weight and fragmentation pathway of standards was introduced to investigate the diterpenoid alkaloids in four dried root tubers of A. kusnezoffii Reichb., A. carmichaelii Radix., A. pendulum Busch., and A. brachypodum Diels. Thirty‐two diterpenoid alkaloids were identified by the molecular networking platform. Their structures were determined by tandem mass spectrometry fragmentation comparisons, and structures that connect fatty acyl groups with different modifications at the C‐8 position which in previous studies paid little attention may have better digestion and absorption behavior in drug clinic uses. This work provides a basis for further understanding the clinical efficacy of Aconitum herbs.

Inhibition of SLC7A11-GPX4 signal pathway is involved in aconitine-induced ferroptosis in vivo and in vitro

Ethnopharmacological relevanceAconitum species, with a long history of traditional application, were applied to treat rheumatism, arthritis, stroke, and pain in Chinese medical practice. However, misuse of Aconitum species may induce central nervous toxic effects, such as numbness, vomiting, and even coma. Aconitine has been proved to be the main toxic component of Aconitum plants. Neurotoxicity is the main toxic effect of aconitine, while the underlying mechanism of aconitine remains unclear. Aim of the studyThe purpose of the study is to explore the effects and molecular mechanism of ferroptosis caused by aconitine in vivo and in vitro. Materials and methodsSix-dpf zebrafish larvae and SH-SY5Y cells were treated with different concentrations of aconitine for 24 h. Inhibitors treatment, e.g. pretreatment with Necrostain-1 (Nec-1) and Z-VZD-FMK for 12 h, or with Ferrostain-1 (Fer-1) for 4 h, were involved in the identification of aconitine-induced ferroptosis. Transient transfection experiment was conducted to explore the effects of SLC7A11 in the process of aconitine-induced ferroptosis. The effects of aconitine on morphological changes, lipid peroxidation, ferrous ion, and ferroptosis were detected by transmission electron microscope, flow cytometry, confocal microscopy, enzyme-linked immunosorbent assay and western blotting. ResultsIn SH-SY5Y cells, morphological changes including shrunken mitochondria, increased mitochondrial membranes density and ruptured mitochondrial membranes were captured in aconitine-treated group. The cell viability and GSH content dose-dependently declined, levels of lipid reactive oxygen species (ROS), malondialdehyde (MDA), and ferrous ion significantly increased after aconitine exposure for 24 h. Ferroptosis inhibitor Fer-1 pretreatment effectively increased cell viability, GSH content, and decreased levels of MDA and lipid peroxidation, suggesting that aconitine induced ferroptosis. In addition, the protein expression of SLC7A11 and GPX4 were improved after Fer-1 preincubation, which indicated that aconitine triggered ferroptosis via the inhibition of SLC7A11 and the inactivation of GPX4. Ferroptotic characteristics, including GSH depletion and lipid peroxidation accumulation, were alleviated via overexpression of SLC7A11 to increase protein expression of GPX4. In zebrafish experiment, GSH depletion, lipid peroxidation accumulation, iron overload, and the decreased protein expression of SLC7A11 and GPX4 were also induced in zebrafish larvae after aconitine exposure. Taken together, aconitine triggered ferroptotic cell death via inhibiting SLC7A11/GPX4 signal pathway in vivo and in vitro. ConclusionAll results indicated that aconitine triggered ferroptosis of SH-SY5Y cells and zebrafish larvae nerve cells, which involved the inhibition of SLC7A11/GPX4 signal pathway mediated by lipid peroxidation damage and iron overload.

Aconitum coreanum Rapaics: Botany, traditional uses, phytochemistry, pharmacology, and toxicology

Abstract The present review summarizes the multifaceted uses and recent findings regarding the phytochemistry, traditional use, pharmacology, and toxicity of the extracts and compounds of Aconitum coreanum Rapaics (Ranunculaceae) for the first time to facilitate further research and exploitation of these types of compounds and the utilization of A. coreanum plants. A. coreanum is one of the most important medicinal Aconitum species and has been traditionally and popularly used in China and other Asian countries for the treatment of headaches and migraines, Bi syndrome induced by wind, cold and dampness, and facial paralysis. Phytochemical studies have led to the isolation of 55 distinct small molecule compounds from A. coreanum, most of which are diterpenoid alkaloids. Related pharmacological studies have focused primarily on the antiarrhythmic, anti-inflammatory, analgesic, and anticancer activities of A. coreanum and its derived drugs. Alkaloids have been demonstrated to be the main active ingredients in this plant. In particular, hetisine-type DAs, mainly Guan-fu base A and its analogues, which possess prominent antiarrhythmic effects, other effects, and hypotoxicity, could be regarded as the representative constituents of A. coreanum. Polysaccharides from A. coreanum also displayed broad bioactivities, demonstrating great potential for further research and exploitation. However, few of the current studies have examined the main active components in A. coreanum from different regions. In addition, most of the pharmacological studies on A. coreanum polysaccharides were carried out using crude or poorly characterized fractions. Finally, reliable analytical methods and deeper studies on the toxicity of the compounds from A. coreanum are needed to ensure the safe usage of these products.

Climate change adversely affects the medicinal value of Aconitum species in Alpine region of Indian Himalaya

Atmospheric CO 2 has an apparent impact on plant growth and physiological processes, especially at higher altitudes. Generally considered to boost photosynthetic rate and biomass accumulation, the effects of elevated CO 2 (eCO 2 ) have been shown to vary amongst different species. The present study explored the effects of eCO 2 on two native Himalayan alpine species viz., Aconitum balfourii and A. heterophyllum of the botanical family Ranunculaceae , known for their potent medicinal properties . Both the species were grown inside open-top chambers and treated with eCO 2 (650 ppm; likely scenario by the year 2100 under RCP6) for three growing seasons along with ambient controls. The primary, secondary (Alkaloids) metabolites, tissue nitrogen (N), antibacterial and antioxidant activity of the experimental plants were examined. In both the species under eCO 2 , total soluble sugars (TSS) were found increased whereas starch content decreased. The secondary metabolites (specific and total alkaloids) and plant N were found declined under elevated CO 2 and the antibacterial activity of the plant extracts from eCO 2 also subsided. However, an increase in the proline content, lipid peroxidation and antioxidant activity was found under eCO 2 . Our results thus conclude a reduction in secondary metabolites of Aconites due to eCO 2 exposure which can not only affect their survival under extreme environmental conditions but also alter the antimicrobial potency against various pathogens. These significant negative plant responses may ultimately impact trade, economy and industrial application of such herbal drugs. • Aconitum species which are rich in alkaloids, were grown under elevated CO 2 (eCO 2 ). • Content of total alkaloid and specific alkaloids both declined under eCO 2 . • Bioactivity of the plants growing under eCO 2 also reduced against human pathogens. • Source-sink imbalance was observed with lesser starch and higher sugars under eCO 2 .