Comparative transcriptome revealed the molecular responses of Aconitum carmichaelii Debx. to downy mildew at different stages of disease development.

BACKGROUND: Aconitum carmichaelii Debx. has been widely used as a traditional medicinal herb for a long history in China. It is highly susceptible to various dangerous diseases during the cultivation process. Downy mildew is the most serious leaf disease of A. carmichaelii, affecting plant growth and ultimately leading to a reduction in yield. To better understand the response mechanism of A. carmichaelii leaves subjected to downy mildew, the contents of endogenous plant hormones as well as transcriptome sequencing were analyzed at five different infected stages. RESULTS: The content of 3-indoleacetic acid, abscisic acid, salicylic acid and jasmonic acid has changed significantly in A. carmichaelii leaves with the development of downy mildew, and related synthetic genes such as 9-cis-epoxycarotenoid dioxygenase and phenylalanine ammonia lyase were also significant for disease responses. The transcriptomic data indicated that the differentially expressed genes were primarily associated with plant hormone signal transduction, plant-pathogen interaction, the mitogen-activated protein kinase signaling pathway in plants, and phenylpropanoid biosynthesis. Many of these genes also showed potential functions for resisting downy mildew. Through weighted gene co-expression network analysis, the hub genes and genes that have high connectivity to them were identified, which could participate in plant immune responses. CONCLUSIONS: In this study, we elucidated the response and potential genes of A. carmichaelii to downy mildew, and observed the changes of endogenous hormones content at different infection stages, so as to contribute to the further screening and identification of genes involved in the defense of downy mildew.

The acute toxic effect of Chinese medicine Fuzi is exacerbated in kidney yang deficiency mice due to metabolic difference.

ETHNOPHARMACOLOGICAL RELEVANCE: The proper application of toxic medicines is one of the characteristics of traditional Chinese medicines, and the use of traditional Chinese medicines follows the principle of dialectical treatment. It is necessary to combine different "syndrome" or "disease" states with the toxicity of traditional Chinese medicines to form a reliable toxicity evaluation system. Fuzi, the lateral root of Aconitum carmichaelii Debx, is recognized as a panacea for kidney yang deficiency syndrome, however, its toxic effects significantly limit its clinical application. AIM OF THE STUDY: Herein, our research aimed to explore the toxic effects of Fuzi on syndrome models, and tried to reveal the underlying mechanisms. MATERIALS AND METHODS: Firstly, the mouse model of kidney yang deficiency syndrome was established through intramuscular injection of 25 mg/kg hydrocortisone per day for 10 consecutive days. Then, the acute toxicity of Fuzi in normal mice and kidney yang deficiency model mice was explored. Finally, the plasma metabolite concentrations and liver CYP3A4 enzyme activity were analyzed to reveal the possible mechanisms of the different pharmacological and toxicological effects of Fuzi in individuals with different physical constitutions. RESULTS: It was found that the treatment with Fuzi (138 g/kg) had serious toxic effects on kidney yang deficiency mice, leading to the death of 80% of the mice, whereas it showed no lethal toxicity in normal mice. This indicates that Fuzi induced greater toxicity in kidney yang deficiency mice than in normal ones. The liver CYP3A4 enzyme activity in kidney yang deficiency mice was decreased by 20% compared to the controls, resulting in slower metabolism of the toxic diester diterpenoid alkaloids in Fuzi. CONCLUSION: In conclusion, our study showed that changes of the metabolic enzyme activity in individuals with different syndromes led to different toxic effects of Chinese medicines, emphasizing the crucial importance of considering individual physical syndromes in the clinical application of traditional Chinese medicine, and the significance of conducting safety evaluations and dose predictions on animal models with specific syndromes for traditional Chinese medicines.

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.

Modulation of cellular metabolism and alleviation of bacterial dysbiosis by Aconiti Lateralis Radix Praeparata in non-small cell lung cancer treatment.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a highly prevalent and fatal form of lung cancer. In China, Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), derived from the lateral root of Aconitum carmichaeli Debx. (Ranunculaceae, Aconitum), is extensively prescribed to treat cancer in traditional medicine and clinical practice. However, the precise mechanism by which Fuzi treats NSCLC remains unknown. PURPOSE: This article aims to assess the efficacy of Fuzi against NSCLC and elucidate its underlying mechanism. METHODS: Marker ingredients of Fuzi decoction were quantified using UPLC-TSQ-MS. The effectiveness of Fuzi on NSCLC was evaluated using a xenograft mouse model. Subsequently, a comprehensive approach involving network pharmacology, serum metabolomics, and 16S rDNA sequencing was employed to investigate the anti-NSCLC mechanism of Fuzi. RESULTS: Pharmacological evaluation revealed significant tumour growth inhibition by Fuzi, accompanied by minimal toxicity. Network pharmacology identified 29 active Fuzi compounds influencing HIF-1, PI3K/Akt signalling, and central carbon metabolism in NSCLC. Integrating untargeted serum metabolomics highlighted 30 differential metabolites enriched in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the tricarboxylic acid (TCA) cycle. Targeted serum metabolomics confirmed elevated glucose content and reduced levels of pyruvate, lactate, citrate, α-ketoglutarate, succinate, fumarate, and malate following Fuzi administration. Furthermore, 16S rDNA sequencing assay showed that Fuzi ameliorated the dysbiosis after tumorigenesis, decreased the abundance of Proteobacteria, and increased that of Firmicutes and Bacteriodetes. PICRUSt analysis revealed that Fuzi modulated the pentose phosphate pathway of the gut microbiota. Spearman correlation showed that Proteobacteria and Escherichia_Shigella accelerated the TCA cycle, whereas Bacteroidota, Bacteroides, and Lachnospiraceae_NK4A136_group suppressed the TCA cycle. CONCLUSIONS: This study firstly introduces a novel NSCLC mechanism involving Fuzi, encompassing energy metabolism and intestinal flora. It clarifies the pivotal role of the gut microbiota in treating NSCLC and modulating the TCA cycle. Moreover, these findings offer valuable insights for clinical practices and future research of Fuzi against NSCLC.

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.

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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.

OBJECTIVES: Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. METHODS: Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. KEY FINDINGS: In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1ß, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. CONCLUSIONS: FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis.

Unlocking the hidden potential: Enhancing the utilization of stems and leaves through metabolite analysis and toxicity assessment of various parts of Aconitum carmichaelii.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves. AIM OF THE STUDY: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications. MATERIALS AND METHODS: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites. RESULTS: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers. CONCLUSION: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.

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.

Therapeutic Potentials of Aconite-like Alkaloids: Bioinformatics and Experimental Approaches.

Compounds from plants that are used in traditional medicine may have medicinal properties. It is well known that plants belonging to the genus Aconitum are highly poisonous. Utilizing substances derived from Aconitum sp. has been linked to negative effects. In addition to their toxicity, the natural substances derived from Aconitum species may have a range of biological effects on humans, such as analgesic, anti-inflammatory, and anti-cancer characteristics. Multiple in silico, in vitro, and in vivo studies have demonstrated the effectiveness of their therapeutic effects. In this review, the clinical effects of natural compounds extracted from Aconitum sp., focusing on aconitelike alkaloids, are investigated particularly by bioinformatics tools, such as the quantitative structure- activity relationship method, molecular docking, and predicted pharmacokinetic and pharmacodynamic profiles. The experimental and bioinformatics aspects of aconitine's pharmacogenomic profile are discussed. Our review could help shed light on the molecular mechanisms of Aconitum sp. compounds. The effects of several aconite-like alkaloids, such as aconitine, methyllycacintine, or hypaconitine, on specific molecular targets, including voltage-gated sodium channels, CAMK2A and CAMK2G during anesthesia, or BCL2, BCL-XP, and PARP-1 receptors during cancer therapy, are evaluated. According to the reviewed literature, aconite and aconite derivatives have a high affinity for the PARP-1 receptor. The toxicity estimations for aconitine indicate hepatotoxicity and hERG II inhibitor activity; however, this compound is not predicted to be AMES toxic or an hERG I inhibitor. The efficacy of aconitine and its derivatives in treating many illnesses has been proven experimentally. Toxicity occurs as a result of the high ingested dose; however, the usage of this drug in future research is based on the small quantity of an active compound that fulfills a therapeutic role.

Research on the effects of processing Heishunpian from Aconiti lateralis radix praeparata on components and efficacy using the "step knockout" strategy.

Heishunpian is obtained through complex processing of Aconiti lateralis radix praeparata. However, the impact of each processing step on chemical compositions and pharmacological activities is still unclear. The mechanism of the processing needs to be further studied. The samples were all prepared using the "step knockout" strategy for UPLC-QTOF-MS analysis, and analgesic and anti-inflammatory efficacy evaluation. Each sample was analyzed by UPLC-QTOF-MS to determine the component differences. The hot plate test and acetic acid writhing test were used to evaluate the analgesic effect. Anti-inflammatory efficacy was evaluated by xylene-induced ear edema test. The correlation between components and efficacies was studied to screen the effective components for further investigating the processing of Heishunpian. Mass spectrum analysis results showed that 49 components were identified, and it appeared that brine immersion and rinsing had a great influence on the components. In the hot plate test, ibuprofen and Heishunpian had the most significant effect, while ibuprofen and the sample without rinsing showed the best efficacy for the acetic acid writhing test. The sample without dyeing had the best effect on ear edema. The correlation analysis indicated that mesaconine, aconine, 3-deoxyaconine, delbruine, and asperglaucide were potentially considered effective analgesic components. It is not recommended to remove brine immersion and rinsing. Boiling and steaming are necessary processes that improve efficacy. Dyeing, which does not have a significant impact on components and efficacy, may be an unnecessary process. This research has been of great significance in identifying anti-inflammatory and analgesic components and optimizing processing for Heishunpian.

Investigations on the morpho-anatomy and histochemistry of Aconitum napellus L.

Aconitum napellus L. is a popular medicinal plant extensively used in homeopathy. This article provides detailed morphology and microscopy, including the anatomical and histochemical features of the herb, to aid authentication and quality control. In cross-section, the root in secondary growth shows the phloem surrounded by pericyclic fibers and a well-developed xylem. The stem is irregular in outline, displaying unicellular trichomes and many free collateral vascular bundles encircling the pith. The leaf is dorsiventral, hypostomatic with anomocytic and anisocytic stomata, and shows non-glandular trichomes. The floral parts are characterized by uniseriate epidermises, homogeneous mesophyll, anomocytic stomata on the abaxial surface, trichomes, and oval pollen grains. The tissue fragments in powdered herbs show these characteristics and have numerous starch grains with thimble-shaped, linear or star-shaped hilum. The detailed macroscopic and microscopic analysis provided in this study can help in the authentication and quality control of A. napellus raw materials. RESEARCH HIGHLIGHTS: Key anatomical, micromorphological, and microchemical features of Aconitum napellus are described. The results of the study can support the taxonomy of the genus Aconitum. Morphological standardization of the species reported here is helpful in the quality control of this herb.

Structural feature-based strategy for the identification of diterpene alkaloids in Aconitum carmichaeli Debeaux.

The taproot of Aconitum carmichaelii Debeaux (AC), a poisonous Traditional Chinese Medicine, has been widely used to treat joint pain, rheumatism and dysmenorrhea. Fermentation is a traditional drug processing method that reduces toxicity or increases efficacy. However, the chemical composition of AC, especially fermented AC, has not been fully elucidated. Therefore, it is necessary to establish a method to characterize the chemical composition of raw and fermented AC. In this study, a structural feature-based comprehensive strategy was employed to identify the chemical components of raw and fermented AC. A highly selective method consisting of mass defect filtering (MDF), ring double bond (RDB), nitrogen rule, and feature MS fragments filtering was established using UPLC-Q-Orbitrap-MS. By the established method, 230 diterpene alkaloids were characterized in raw AC, including 108 amine, 68 monoester, and 54 diester diterpene alkaloids. 145 of them were potential new compounds. Totals of 466 diterpene alkaloids were identified in fermented AC, including 231 amine, 162 monoester, and 73 diester diterpene alkaloids. 397 of them were potential new compounds. Ester hydrolysis, hydroxylation, and demethylation were the major transformation pathways during fermentation. An integrated approach with highly selective based on the structural feature of analytes was established and applied to identify the chemicals in AC. The strategy showed great performance in improving the accuracy and coverage of the identification by using LC-MS.

Comprehensive insight into the pharmacology, pharmacokinetics, toxicity, detoxification and extraction of hypaconitine from Aconitum plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypaconitine (HA), a diterpenoid alkaloid, mainly derived from Aconitum plants such as Acoitum carmichaeli Debx. And Aconitum nagarum Stapf., has recently piqued significant interest among the scientific community given its multifaceted attributes including anti-inflammatory, anticancer, analgesic, and cardio-protective properties. AIM OF THE STUDY: This review presents a comprehensive exploration of the research advancements regarding the traditional uses, pharmacology, pharmacokinetics, toxicity, and toxicity reduction of HA. It aims to provide a thorough understanding of HA's multifaceted properties and its potential applications in various fields. MATERIALS AND METHODS: A systematic literature search was conducted using several prominent databases including PubMed, Web of Science, NCBI, and CNKI. The search was performed using specific keywords such as "hypaconitine," "heart failure," "anti-inflammatory," "aconite decoction," "pharmacological," "pharmacokinetics," "toxicity," "detoxification or toxicity reduction," and "extraction and isolation." The inclusion of these keywords ensured a comprehensive exploration of relevant studies and enabled the retrieval of valuable information pertaining to the various aspects of HA. RESULTS: Existing research has firmly established that HA possesses a range of pharmacological effects, encompassing anti-cardiac failure, anti-inflammatory, analgesic, and anti-tumor properties. The therapeutic potential of HA is promising, with potential applications in heart failure, ulcerative colitis, cancer, and other diseases. Pharmacokinetic studies suggest that HA exhibits high absorption rates, broad distribution, and rapid metabolism. However, toxic effects of HA on the nerves, heart, and embryos have also been observed. To mitigate these risks, HA needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. Extraction methods for HA most commonly include cold maceration, soxhlet reflux extraction, and ultrasonic-assisted extraction. Despite the potential therapeutic benefits of HA, further research is warranted to elucidate its anti-heart failure effects, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and metabolites. Additionally, the therapeutic effects of HA monomers on inflammation-induced diseases and tumors should be validated in a more diverse range of experimental models, while the mechanisms underlying the therapeutic effects of HA should be investigated in greater detail. CONCLUSION: This review serves to emphasize the therapeutic potential of HA and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the pharmacological properties of HA, with particular emphasis on its anti-cardiac failure and anti-inflammatory activities. Such research endeavors have the potential to unveil novel treatment avenues for a broad spectrum of diseases.

Impacts of climate change and human activity on the potential distribution of Aconitum leucostomum in China.

Aconitum leucostomum is a poisonous grass that disturbs grassland populations and livestock development, and its spread is influenced by climate change and human activities. Therefore, exploring its potential distribution area under such conditions is crucial to maintain grassland ecological security and livestock development. The present study initially selected 39 variables that may influence the spatial distribution of A. leucostomum, including bioclimate, soil, topography, solar radiation, and human footprint data; the variables were screened by Spearman's correlation coefficient and the jackknife method. Twenty variables were finally identified, and three types of models based on the maximum entropy (MaxEnt) model were constructed to predict the distribution of A. leucostomum within China under three shared economy pathways (SSP126, SSP245, and SSP585): A: prediction of environmental variables under the current climate model; B: prediction of environmental variables + human footprint under the current climate model; and C: prediction of environmental variables under the future climate model (including the 2030s, 2050s, and 2070s). The effects of human activities and climate change on the potential geographic distribution of A. leucostomum were explored separately. The results show that precipitation seasonality, human footprint, solar radiation and mean diurnal range are the main factors affecting the distribution of A. leucostomum. Human activities inhibit the spread of A. leucostomum, and climate change promotes its growth, with areas of high suitability and area variation mainly in northern Xinjiang and northern Yunnan. With climate change, in the future, the distribution center of A. leucostomum shows a tendency to migrate to the southeast on the horizontal gradient and to move to higher altitudes on the vertical gradient. This study provides a positive reference value for the control of A. leucostomum and the maintenance of grassland ecological security.

Sensitive quantitation of ultra-trace toxic aconitines in complex matrices by perfusion nano-electrospray ionization mass spectrometry combined with gas-liquid microextraction.

The accurate analysis of ultra-trace (e.g. <10-4 ng/mL) substances in complex matrices is a burdensome but vital problem in pharmaceutical analysis, with important implications for precise quality control of drugs, discovery of innovative medicines and elucidation of pharmacological mechanisms. Herein, an innovative constant-flow perfusion nano-electrospray ionization (PnESI) technique was developed firstly features significant quantitative advantages in high-sensitivity ambient MS analysis of complex matrix sample. More importantly, double-labeled addition enrichment quantitation strategies of gas-liquid microextraction (GLME) were proposed for the first time, allowing highly selective extraction and enrichment of specific target analytes in a green and ultra-efficient (>1000-fold) manner. Using complex processed Aconitum herbs as example, PnESI-MS directly enabled the qualitative and absolute quantitative analysis of the processed Aconitum extracts and characterized the target toxic diester alkaloids with high sensitivity, high stability, wide linearity range, and strong resistance to matrix interference. Further, GLME device was applied to obtain the highly specific enrichment of the target diester alkaloids more than 1000-fold, and accurate absolute quantitation of trace aconitine, mesaconitine, and hypaconitine in the extracts of Heishunpian, Zhichuanwu and Zhicaowu was accomplished (e.g., 0.098 pg/mL and 0.143 pg/mL), with the quantitation results well below the LODs of aconitines from any analytical instruments available. This study built a systematic strategy for accurate quantitation of ultra-trace substances in complex matrix sample and expected to provide a technological revolution in many fields of pharmaceutical research.

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.

A new C19-diterpenoid alkaloid in Aconitum georgei Comber.

Nine diterpenoid alkaloids were isolated from Aconitum georgei Comber belonging to the genus Aconitum in Ranunculaceae family. Their structures were determinated by using HR-ESI-MS and 1 D/2D NMR spectra as geordine (1), yunaconitine (2), chasmanine (3), crassicauline A (4), forestine (5), pseudaconine (6), 14-acetylalatisamine (7), austroconitine B (8), and talatisamine (9). Among them, compound 1 is a previously undescribed aconitine-type C19-diterpenoid alkaloid, and compounds 3, and 5-9 have not previously been isolated from this species. The results of in vitro experiments indicated that new compound 1 possesses mild anti-inflammatory activity, which inhibited the production of NO in LPS-activated RAW 264.7 cells with an inhibition ratio of 29.75% at 50 µM.

[Aconite, in 4.50 from Paddington: Continuous Activation of Voltage-Gated Sodium Channel].

Aconite belongs to the genus Aconitum and the Ranunculaceae family, which contains approximately 300 species worldwide. Aconite, the poison mentioned in Agatha Christie's novel 4.50 from Paddington, contains aconitum alkaloids in all parts of the plant, including the roots, stem, leaves, and flowers. Aconitum alkaloids continuously activate voltage-gated sodium channels in the myocardium, central nervous system, and skeletal muscle. Activated sodium channels trigger automaticity and cause pre-excitation of cardiomyocytes, which precipitates various types of ventricular arrhythmias.