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.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Evaluation of the effects of three different processing methods of aconite on rat metabolites based on high-coverage pseudotargeted metabolomics.

Aconite is the processed product of the seed root of Aconitum carmichaelii Debx. Aconite is a commonly used traditional Chinese medicine, which is generally used after processing. Black aconite, light aconite, and salted aconite are three different processed aconite products. They have the effects of restoring yang and saving energy enemy, dispersing cold, and relieving pain. However, clinical aconite poisoning cases have frequently been reported. In our study, we investigated the effects of three different processed aconite products on the changes of metabolites in vivo. A total of 42 rats were randomly divided into seven groups with six rats in each group. After three consecutive days of intragastric administration of 2.7 g/kg of the aconite-processed product, rat serums were obtained. The rat metabolites were detected using liquid chromatography-tandem mass spectrometry. The altered metabolites related to aconite-processed products were discovered by statistical analysis using metaboanalyst software. Our study is the first time to comprehensively evaluate the effects of three different processed aconite products on rat metabolites based on pseudotargeted metabolomics.

Assessing the Potential of Aconitum Laeve Extract for Biogenic Silver and Gold Nanoparticle Synthesis and Their Biological and Catalytic Applications.

The adoption of green chemistry protocols in nanoparticle (NP) synthesis has exhibited substantial potential and is presently a central focus in research for generating versatile NPs applicable across a broad spectrum of applications. In this scientific contribution, we, for the first time, examined the ability of Aconitum Laeve (A. Laeve) crude extract to synthesize silver and gold nanoparticles (AgNPs@AL; AuNP@AL) and explored their potential applications in biological activities and the catalytic degradation of environmental pollutants. The synthesized NPs exhibited a distinctive surface plasmon resonance pattern, a spherical morphology with approximate sizes of 5-10 nm (TEM imaging), a crystalline architecture (XRD analysis), and potential functional groups identified by FTIR spectroscopy. The antibacterial activity was demonstrated by inhibition zones that measured 16 and 14 mm for the AgNPs@AL and AuNP@AL at a concentration of 80 µg/mL against Staphylococcus aureus and 14 and 12 mm against Escherichia coli, respectively. The antioxidant potential of the synthesized NPs was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Our findings suggest that the AuNP@AL effectively countered the tested radicals considerably, displaying IC50 values of 115.9, 103.54, and 180.85 µg/mL against DPPH, PTIO, and ABTS, respectively. In contrast, the AgNPs@AL showed IC50 values of 144.9, 116.36, and 95.39 µg/mL against the respective radicals. In addition, both the NPs presented significant effectiveness in the photocatalytic degradation of methylene blue and rhodamine B. The overall observations indicate that A. Laeve possesses a robust capability to synthesize spherical nanoparticles, exhibiting excellent dispersion and showcasing potential applications in both biological activities and environmental remediation.

Bioactive polysaccharides in different plant parts of Aconitum carmichaelii.

BACKGROUND: Aconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in traditional Chinese medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non-toxic polysaccharides in this plant have attracted less attention than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were isolated systematically from different plant parts of A. carmichaelii, and their structural features and bioactivity were studied and compared. RESULTS: The neutral fraction isolated from the rootlets differed from those isolated from the lateral and mother roots. It consisted of less starch and more possible mannans, galactans, and/or xyloglucans, being similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type-I rhamnogalacturonan (RG-I) were present in all plant parts of A. carmichaelii. However, more arabinogalactan (AG)-II side chains in the RG-I backbone were present in the aerial parts of the plants, while more amounts of arabinans were found in the roots. Various immunomodulatory effects were observed, determined by complement fixation activity and anti-inflammatory effects on the intestinal epithelial cells of all polysaccharide fractions. CONCLUSION: This study highlighted the diversity of polysaccharides present in A. carmichaelii, especially in the unutilized plant parts, and showed their potential medicinal value. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

[Study on mechanism of Aconitum pendulum in treating rheumatoid arthritis based on toxicity efficacy evaluation and metabonomics].

The study aims to investigate the effects and potential mechanism of raw and processed Aconitum pendulum Busch on rheumatoid arthritis(RA) and analyze their toxicity attenuating and efficacy retaining effects. The bovine type Ⅱ collagen-induced arthritis(CIA) rat model was established. The weight, cardiac index, immune organ index, and arthritis index of the rats were recorded and calculated after administration. ELISA was used to measure the expressions of creatine kinase(CK), cardiac troponin T(cTnT), and multiple factors. The pathological morphological changes in heart tissue and ankle joint tissue were observed by hematoxylin-eosin staining. Connexin 43(Cx43) expression in the hearts of CIA rats was detected via immunohistochemical method. The levels of endogenous metabolites in the serum of CIA rats were detected by UPLC-Q-TOF-MS. Potential biomarkers were screened, and related metabolic pathways were analyzed. The results showed that raw A. pendulum could induce local myocardial fiber degeneration and necrosis, increase the cardiac index, decrease the average positive area of Cx43 expression significantly, and increase the expressions of CK and cTnT in cardiac tissue of rats. Meanwhile, raw A. pendulum could decrease the immune organ index, interleukin-6(IL-6), and other inflammatory cytokine contents in the serum and improve the damaged synovium and joint surface of CIA rats, with toxicity and efficacy coexisting. The Zanba stir-fired A. pendulum could reduce the index of arthritis, immune organ index, and content of IL-6 and inflammatory cytokines in serum and improve damaged synovium and joint surface of CIA rats with no obvious cardiac toxicity, showing significant toxicity attenuating and efficacy retaining effects. A total of 19 potential biomarkers of raw A. pendulum and Zanba stir-fired A. pendulum against RA were screened by serum metabolomics, including glycerophospholipid metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and steroid hormone synthesis. In conclusion, Xizang medicine A. pendulum is preventive and curative for RA. Raw A. pendulum has certain cardiotoxicity, and Zanba stir-fired A. pendulum has significant toxicity attenuating and efficacy retaining effects. The anti-RA mechanism may be related to the regulation of glycerophospholipid and amino acid metabolism.

Postmortem Diffusion of Aconitum Alkaloids and Their Metabolites in Rabbits.

OBJECTIVES: To explore the postmortem diffusion rule of Aconitum alkaloids and their metabolites in poisoned rabbits, and to provide a reference for identifying the antemortem poisoning or postmortem poisoning of Aconitum alkaloids. METHODS: Twenty-four rabbits were sacrificed by tracheal clamps. After 1 hour, the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration. Then, they were placed supine and stored at 25 ℃. The biological samples from 3 randomly selected rabbits were collected including heart blood, peripheral blood, urine, heart, liver, spleen, lung and kidney tissues at 0 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h and 96 h after intragastric administration, respectively. Aconitum alkaloids and their metabolites in the biological samples were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: At 4 h after intragastric administration, Aconitum alkaloids and their metabolites could be detected in heart blood, peripheral blood and major organs, and the contents of them changed dynamically with the preservation time. The contents of Aconitum alkaloids and their metabolites were higher in the spleen, liver and lung, especially in the spleen which was closer to the stomach. The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration. In contrast, the contents of Aconitum alkaloids and their metabolites in kidney were all lower. Aconitum alkaloids and their metabolites were not detected in urine. CONCLUSIONS: Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits, diffusing from high-content organs (stomach) to other major organs and tissues as well as the heart blood. The main mechanism is the dispersion along the concentration gradient, while urine is not affected by postmortem diffusion, which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

An Optimized Two-Dimensional Quantitative Nuclear Magnetic Resonance Strategy for the Rapid Quantitation of Diester-Type C19-Diterpenoid Alkaloids from Aconitum carmichaelii.

With the development of nuclear magnetic resonance (NMR) spectrometers and probes, two-dimensional quantitative nuclear magnetic resonance (2D qNMR) technology with a high signal resolution and great application potential has become increasingly accessible for the quantitation of complex mixtures. However, the requirement that the relaxation recovery time be equal to at least five times T1 (longitudinal relaxation time) makes it difficult for 2D qNMR to simultaneously achieve high quantitative accuracy and high data acquisition efficiency. By comprehensively using relaxation optimization and nonuniform sampling, we successfully established an optimized 2D qNMR strategy for HSQC experiments at the half-hour level and then accurately quantified the diester-type C19-diterpenoid alkaloids in Aconitum carmichaelii. The optimized strategy had the advantages of high efficiency, high accuracy, good reproducibility, and low cost and thus could serve as a reference to optimize 2D qNMR experiments for quantitative analysis of natural products, metabolites, and other complex mixtures.

Spatial distribution and comparative analysis of Aconitum alkaloids in Fuzi using DESI-MSI and UHPLC-QTOF-MS.

Aconitum L. poisoning is a major type of poisoning caused by herbal medicines in many countries. However, despite its toxicity, Aconitum L. is still used because of its therapeutic value. Fuzi, the lateral root of Aconitum L., is one of the most important pharmacological parts. It is necessary for rational medication to figure out the types and contents of toxic Aconitum alkaloids (AAs) in Fuzi and its processed products. The present study aims to investigate the spatial distribution of toxic AAs in Fuzi and the quantification of AAs in various processing products through mass spectrometry methods. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to directly image the sections of raw Fuzi. The results showed a high content of diester alkaloids (DAs) and a relatively uniform distribution in the sections, while the content of monoester alkaloids (MAs) was low and uneven in the sections, distributed in the cortex, epidermis, vascular column, and other parts of the tissues. The content of non-ester alkaloids (NAs) was relatively minimum, and most of the NAs were distributed in the vascular column and the tightly connected cortex of the tissue. To further investigate the difference between raw and processed Fuzi, 60 known compounds were identified using UHPLC-QTOF-MS. The total contents of alkaloids in 7 processed Fuzi were lower than that in Shengfupian (SFP). Paofupian (PFP), Paotianxiong (PTX), Paofupian (PFP*), Danfupian (DFP), and Shufupian (SFP*) were the least similar. Zhengfupian (ZFP) and Chaofupian (CFP) had significantly reduced toxicity and increased efficacy compared with other processed products because the contents of active alkaloids in other processed products were also reduced. Understanding the distribution of metabolites and the composition changes after processing can guide users and herbal manufacturers to carefully choose the relatively safe and better therapeutic species of Fuzi. The information gathered from this study can contribute towards the improved and effective management of therapeutically important, nonetheless toxic, drugs such as Aconitum L.

Doped nanomaterial facilitates 3D printing target plate for rapid detection of alkaloids in laser desorption/ionization mass spectrometry.

This work aims to rapidly detect toxic alkaloids in traditional Chinese medicines (TCM) using laser desorption ionization mass spectrometry (LDI-MS). We systematically investigated twelve nanomaterials (NMs) as matrices and found that MoS2 and defect-rich-WO3 (D-WO3) were the best NMs for alkaloid detection. MoS2 and D-WO3 can be used directly as matrices dipped onto conventional ground steel target plates. Additionally, they can be conveniently fabricated as three-dimensional (3D) NM plates, where the MoS2 or D-WO3 NM is doped into resin and formed using a 3D printing process. We obtained good quantification of alkaloids using a chemothermal compound as an internal standard and detected related alkaloids in TCM extracts, Fuzi (Aconiti Lateralis Radix Praeparata), Caowu (Aconiti Kusnezoffii Radix), Chuanwu (Aconiti Radix), and Houpo (Magnoliae Officinalis Cortex). The work enabled the advantageous "dip and measure" method, demonstrating a simple and fast LDI-MS approach that achieves clean backgrounds for alkaloid detection. The 3D NM plates also facilitated mass spectrometry imaging of alkaloids in TCMs. This method has potential practical applications in medicine and food safety. Doped nanomaterial facilitates 3D printing target plate for rapid detection of alkaloids in laser desorption/ionization mass spectrometry.

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.

Metabolite Profiling of Talatisamine in Heart Tissue After Oral Administration and Analysis of Cardiac Bioactivities.

The lateral roots of the Aconitum carmichaelii ("Fuzi") have been used for centuries as a cardiotonic in China. The diterpenoid alkaloid talatisamine (TA) is a major bioactive component of Fuzi, but the identity and bioactivities of the TA metabolites have not been examined in detail. In this study, metabolite profiling of TA was performed in rat heart by UPLC-MS following oral administration. Metabolites were identified by comparing protonated molecules, fragmentation patterns, and chromatographic behaviors with those of standard compounds. Metabolites of TA were then prepared and tested for cardiotonic activity on isolated frog hearts. The metabolite cammaconine, a C19 diterpenoid alkaloid with a hydroxyl group at C-18, exhibited substantial cardiotonic activity during frog heart perfusion. To further investigate the structure-cardiac effect relationships, a series of C19-diterpenoid alkaloids with 18-OH were prepared. Eight tested compounds (5: -12: ) demonstrated measurable cardioactivity, of which compound 5: with an N-methyl group and compound 7: with a methoxy at C-16 showed stronger effects on ventricular contraction than the other compounds. Thus, 18-OH is a critical structural feature determining cardiotonic activity, and efficacy is improved by the presence of N-methyl or methoxy at C-16. Preliminary mechanistic studies suggested that the cardiotonic effect of compound 5: is mediated by enhanced cellular calcium influx. Metabolites of TA with these structural features may be useful therapeutics to prevent heart failure.

Comparative Pharmacokinetic Investigation on Multiple Active Aminoalcohol-Diterpenoid Alkaloids after Single Oral Administrations of Monomers and Aqueous Extract of Fuzi (Aconiti Lateralis Radix Praeparata) by UFLC-MS/MS.

To further study the aminoalcohol-diterpenoid alkaloids (ADAs) in Fuzi (Aconiti Lateralis Radix Praeparata), a simple and sensitive UFLC-MS/MS method was established and validated for the determination of five ADAs, aconine, mesaconine, hypaconine, deoxyaconine and fuziline, in rat plasma to compare the pharmacokinetic characteristics of pure ADAs and Fuzi decoction. After precipitating protein with methanol, plasma samples were isolated at 0.5 mL/min flow rate on Waters Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm). The mobile phase was composed of 0.1% formic acid-water and methanol with gradient elution. Mass spectrometric inspection was conducted on a 5500 UFLC-MS/MS system with an electrospray ionization source in patterns of positive ion and multiple reaction-monitoring (MRM). All calibration curves were proved to have acceptable linearity (r2 > 0.99) in linear ranges. Intra-day and inter-day precision and the accuracy met the requirements. The matrix effects of all analytes were between 85% and 115% of three concentration levels. This method has been under verification for comparative pharmacokinetic research after oral administration between aqueous extract of Fuzi and single pure ADAs. The results demonstrated that there are evident pharmacokinetic discrepancies between them, and administration in the extract form instead of pure form may contribute to higher absorption.

Polysaccharides and Bioactive Phenolics from Aconitum septentrionale Roots.

Aconitum septentrionale is known to contain toxic diterpene alkaloids, while other bioactive compounds in the plant remain unclear. The aim of this study was to explore the phenolic compounds and polysaccharides from the water extract of A. septentrionale roots. Fifteen phenolic compounds were isolated and identified by NMR and MS, including fourteen known and one new dianthramide glucoside (2-[[2-(ß-D-glucopyranosyloxy)-5-hydroxybenzoyl]amino]-4,5-dihydroxybenzoic acid methyl ester, 14). One neutral (complex of glucans with minor amounts of mannans) and two acidic polysaccharide fractions (complexes of pectic polysaccharides and glucans) were also obtained. Hydroxytyrosol (1), hydroxytyrosol-1-O-ß-glucoside (2) and bracteanolide A (7) inhibited the release of nitric oxide by dendritic cells. Magnoflorine (8) and 2-[[2-(ß-D-glucopyranosyloxy)-5-hydroxybenzoyl]amino]-5-hydroxybenzoic acid methyl ester (12) inhibited 15-lipoxygenase, and bracteanolide A (7) was a moderate inhibitor of xanthine oxidase. This study is the first to describe the diversity of phenolics and polysaccharides from A. septentrionale and their anti-inflammatory and anti-oxidant activities.

Four New C19 -Diterpenoid Alkaloids from Aconitum nagarum Stapf.

Four new aconitine-type C19 -diterpenoid alkaloids, were isolated from the roots of Aconitum nagarum Stapf which were named as nagarutines A-D (1-4), together with eleven known compounds (5-15). The structures of the compounds were identified by IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were tested for the inhibitory effect on LPS induced NO production in RAW 264.7 macrophages, compound 7 showed moderate anti-inflammatory activity effect and Inhibition rate is about 44.50%.

Root endophytic bacterial community composition of Aconitum carmichaelii debx. from three main producing areas in China.

Aconitum carmichaelii Debx. is famous for the bioactive aconitum alkaloids as traditional Chinese medicine. Endophytic bacteria play vital roles in plant growth, health, and the production of secondary metabolites such as alkaloids. In this study, we employed 16 S rRNA amplicon high-throughput sequencing to determine the root endophytic bacterial community of A. carmichaelii Debx. collected from three main producing areas including the geo-authentic area in China, high performance liquid chromatography to measure the contents of six bioactive alkaloids and correlation analysis to explore the relationship among environmental factors, alkaloids contents, and endophytic bacterial community. The results indicated that the root core microbiota of A. carmichaelii Debx. was dominated by Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Root endophytic bacterial community in the geo-authentic area was distinct from the other two regions. Soil nitrogen contents, organic matter, and temperature were the main factors contributing to the endophytic bacterial community structure. Significant correlation was found between alkaloids contents and some bacterial genera. Particularly, the abundance of Lactobacillus was positively correlated with the contents of benzoyl-mesaconitine and benzoyl-aconine. This study provided the first insight into the root endophytic bacterial community composition of A. carmichaelii Debx., and can direct further isolation of functional bacterial strains.

Multi-conformers caused by conformational change of A-ring in the C18- and C19-N-dealkyl diterpenoid alkaloids.

This paper describes a rare phenomenon of multi-conformers caused by conformational change of A-ring in the C18- and C19- N-dealkyl diterpenoid alkaloids. The possible reasons for the generation of multiple conformational isomers are complex, which could be affected by the substituents at C-1, C-3, C-13, C-14, and C-15, pH, solvents, the intramolecular hydrogen bond between 1α-OCH3/1α-OH and N-H groups, acid-base treatment, preparation methods, and work-up procedures.

Two new bis-diterpenoid alkaloids from Aconitum weixiense.

Further investigation on the roots of Aconitum weixiense led to the isolation of two new bis-diterpenoid alkaloids, named as weisaconitines E and F (1-2), which were elucidated by IR, HR-ESI-MS, 1D- and 2D-NMR analyses. Their structures are characterized as denudatine-atisine-type bis-diterpenoid alkaloids.

Antinociceptive diterpenoid alkaloids from the roots of Aconitum austroyunnanense.

A phytochemical investigation on the roots of Aconitum austroyunnanense afforded three undescribed aconitine-type C19-diterpenoid alkaloids, austroyunnanines A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. The isolated alkaloids were tested in vivo for their antinociceptive properties. Consequently, austroyunnanine B (2) exhibited significant antinociceptive effect and its ID50 value (48.0 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Antinociceptive C19-diterpenoid alkaloids from the roots of Aconitum nagarum.

Three new C19-diterpenoid alkaloids, nagarumines A-C (1-3), together two known alkaloids, deoxyaconitine (4) and N-deethyldeoxyaconitine (5), were isolated from the roots of Aconitum nagarum. The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as high resolution mass spectrometry. The in vivo pharmacological studies revealed that nagarumine C (3) possessed comparable antinociceptive activity (ED50 = 76.0 µmol/kg) with the positive control drugs aspirin and acetaminophen.