ABSTRACT
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.
Subject(s)
Aconitum , Phylogeny , Aconitum/genetics , Aconitum/chemistry , Aconitum/metabolism , Organelles/genetics , TibetABSTRACT
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.
Subject(s)
Aconitum , Plant Diseases , Plant Growth Regulators , Transcriptome , Plant Diseases/microbiology , Plant Diseases/genetics , Aconitum/genetics , Plant Growth Regulators/metabolism , Plant Leaves/microbiology , Plant Leaves/genetics , Gene Expression Profiling , Gene Expression Regulation, PlantABSTRACT
Chitosan (CTS) is recognized for enhancing a plant's resilience to various environmental stresses, such as salinity and drought. Moreover, salicylic acid (SA) is acknowledged as a growth regulator involved in addressing metal toxicity. However, the effectiveness of both compounds in mitigating Cr-induced stress has remained relatively unexplored, especially in the case of Aconitum napellus, a medicinally and floricultural important plant. Therefore, the primary objective of this study was to investigate the potential of CTS and SA in alleviating chromium (Cr)-induced stress in A. napellus. To address these research questions, we conducted a controlled experiment using potted plants to evaluate the individual and combined impacts of CTS and SA on plants exposed to Cr stress. Foliar application of CTS (0.4 g/L) or SA (0.25 mmol/L) led to significant improvements in the growth, chlorophyll content, fluorescence, and photosynthetic traits of A. napellus plants under Cr stress. The most notable effects were observed with the combined application of CTS and SA, resulting in increases in various morphological parameters, such as shoot length (2.89% and 7.02%) and root length (27.75% and 3.36%) under the Cr 1 and Cr 2 treatments, respectively. Additionally, several physiological parameters, such as chlorophyll a (762.5% and 145.56%), chlorophyll b (762.5% and 145.56%), carotenoid (17.03% and 28.57%), and anthocyanin (112.01% and 47.96%) contents, were notably improved under the Cr 1 and Cr 2 treatments, respectively. Moreover, the combined treatment of CTS and SA improved the fluorescence parameters while decreasing the levels of enzymatic antioxidants such as catalase (27.59% and 43.79%, respectively). The application also notably increased osmoprotectant parameters, such as the total protein content (54.11% and 20.07%) and the total soluble sugar content (78.17% and 49.82%) in the leaves of A. napellus in the Cr 1 and 2 treatments, respectively. In summary, these results strongly suggest that the simultaneous use of exogenous CTS and SA is an effective strategy for alleviating the detrimental effects of Cr stress on A. napellus. This integrated approach opens promising avenues for further exploration and potential implementation within agricultural production systems.
Subject(s)
Aconitum , Chitosan , Chromium , Photosynthesis , Salicylic Acid , Salicylic Acid/pharmacology , Chitosan/pharmacology , Photosynthesis/drug effects , Aconitum/drug effects , Aconitum/physiology , Chlorophyll/metabolism , Stress, Physiological/drug effectsABSTRACT
RATIONAL: Aconiti Lateralis Radix Praeparata (AC) is a traditional Chinese medicine with a long history of use. However, the current research on the material basis of AC and its processed products is still not comprehensive, especially the changes in lipo-diterpenoid alkaloids (LDAs) that can be hydrolyzed into diester-diterpenoid alkaloids in AC before and after processing. This study aimed to provide material basis guidance for the clinical use of AC and its processed products by comprehensively analyzing the changes in substances between AC and its processed products. METHODS: An ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) approach was optimized to chemical profiling. The MS data were processed using molecular networking combined with the in-house library database to fast characterize the compounds. Multivariate statistical methods were adopted to determine the dissimilarities of components in AC and its processed products. RESULTS: A total of 310 compounds were tentatively identified from AC, including 109 potential new alkaloids, of which 98 were potential novel LPAs. A metabolomics approach was applied to find the characteristic marker components. As a result, 52 potential chemical markers were selected to distinguish the AC samples of different extraction methods and 42 potential chemical markers for differentiating between AC and its processed products were selected. CONCLUSION: The results indicate that UHPLC/Q-TOF-MS/MS and Global Natural Products Social Molecular Networking coupled with multivariate analysis strategies was a powerful tool to rapidly identify and screen the chemical markers of alkaloids between the AC samples and its processed products. These results also indicate that the toxicity of water extracts of AC and its processed products were decreased. This research not only guides the clinical safe use of AC and its processed products, but also extends the application of the molecular networking strategy in traditional herbal medicine.
Subject(s)
Aconitum , Alkaloids , Drugs, Chinese Herbal , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Alkaloids/analysis , Alkaloids/chemistry , Tandem Mass Spectrometry/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Aconitum/chemistry , Multivariate Analysis , HumansABSTRACT
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.
Subject(s)
Aconitum , Animals , Aconitum/genetics , DNA Barcoding, Taxonomic , Himalayas , DNA , Endangered SpeciesABSTRACT
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.
Subject(s)
AMP-Activated Protein Kinases , Aconitine , Cardiotoxicity , Histone Deacetylases , Animals , Mice , Cardiotoxicity/metabolism , Cardiotoxicity/etiology , Histone Deacetylases/metabolism , AMP-Activated Protein Kinases/metabolism , Male , Humans , Aconitum/chemistry , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Drugs, Chinese Herbal/pharmacologyABSTRACT
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.
Subject(s)
Aconitum , Drugs, Chinese Herbal , Rats , Animals , Aconitum/chemistry , Drugs, Chinese Herbal/analysis , Plant Roots/chemistry , Medicine, Chinese Traditional , Chromatography, Liquid , Metabolomics/methodsABSTRACT
Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.
Subject(s)
Aconitum , Gerbillinae , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Animals , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Male , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stroke/metabolism , Stroke/prevention & control , Signal Transduction/drug effects , Oxidative Stress/drug effects , Ischemic Stroke/metabolism , Ischemic Stroke/prevention & controlABSTRACT
Aconiti Lateralis Radix Praeparata (Fuzi, FZ) is a frequently utilized traditional Chinese medicine (TCM) in clinical settings. However, its toxic and side effects, particularly cardiac injury, are apparent, necessitating processing before use. To investigate the mechanism of toxicity induced by absorbed components and the mitigating effect of processed FZ, we established a comprehensive method combining serum pharmacochemistry and a network pharmacology approach. In total, 31 chemical components were identified in the plasma, with a general decrease in response intensity observed for these components in processed FZ. Subsequently, four components were selected for network pharmacology analysis. This analysis revealed 150 drug action targets and identified 1162 cardiac toxicity targets. Through intersection analysis, 41 key targets related to cardiac toxicity were identified, along with 9 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The most critical targets identified were AKT1, MTOR, and PARP1. The key biological pathways implicated were adrenergic signaling in cardiomyocytes, proteoglycans in cancer, and the calcium signaling pathway. Significant differences were observed in histological staining and biochemical indicators in the cardiac tissue of rats treated with FZ, indicating that processing could indeed reduce its cardiotoxicity. Indeed, this article presents a valuable strategy for elucidating the toxification mechanism of toxic TCM.
Subject(s)
Aconitum , Drugs, Chinese Herbal , Network Pharmacology , Rats, Sprague-Dawley , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Rats , Network Pharmacology/methods , Aconitum/chemistry , Male , TOR Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Cardiotoxicity/etiology , Poly (ADP-Ribose) Polymerase-1/metabolism , DiterpenesABSTRACT
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 inâ 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±0.15â µg/ml) followed by A. ferox (IC50 =12.912±1.87â 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.
Subject(s)
Aconitine/analogs & derivatives , Aconitum , Drugs, Chinese Herbal , Aconitine/pharmacology , Aconitine/analysis , Sikkim , Himalayas , Chromatography, High Pressure Liquid/methods , IndiaABSTRACT
Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2Dâ NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19â mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.
Subject(s)
Aconitum , Alkaloids , Diterpenes , Aconitum/chemistry , Diterpenes/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Tetranychidae/drug effects , Molecular Structure , Molecular Conformation , Crystallography, X-Ray , Insecticides/chemistry , Insecticides/isolation & purification , Insecticides/pharmacology , Models, MolecularABSTRACT
INTRODUCTION: Aconiti lateralis radix praeparata (ALRP), the sub root of Aconitum carmichaelii Debx., is a traditional Chinese medicine with good pharmacological effects. Heishunpian (HSP), prepared through the process of brine immersing, boiling, rinsing, dyeing, and steaming ALRP is one of the most widely used forms of decoction pieces in clinical practice. OBJECTIVES: This study aims to investigate the mechanisms of component changes and transformations during the processing from ALRP to HSP, and to screen for their quality markers through UHPLC-QTOF-MS analysis. METHODS: Samples from ALRP to HSP during processing were prepared and analyzed by UHPLC-QTOF-MS. By comparing the differences between before and after each processing step, the purpose of processing and the transformation of components during processing were studied. In addition, multiple batches of ALRP and HSP were determined, and potential quality markers were screened. RESULTS: Through the analysis of ALRP and five key processing samples, 55 components were identified. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and boiling caused a slight loss of components. Some components were enhanced during the steaming process. Combining the screened differences components between multiple ALRP and HSP, 10 components were considered as potential quality biomarkers. CONCLUSION: This study found that the adjacent hydroxyl groups of the ester group may have a positive impact on the hydrolysis of the ester group, and 10 quality markers were preliminarily screened. It provides a reference for quality control and clinical application of ALRP and HSP.
Subject(s)
Aconitum , Aconitum/chemistry , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Plant Roots/chemistry , Mass Spectrometry/methods , Quality ControlABSTRACT
BACKGROUND: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly. METHOD: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened. RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.
Subject(s)
Aconitum , Drugs, Chinese Herbal , Kidney , Mass Spectrometry , Aconitum/chemistry , Kidney/drug effects , Animals , Drugs, Chinese Herbal/toxicity , Drugs, Chinese Herbal/chemistry , Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Aconitine/analogs & derivatives , Aconitine/toxicity , Protein Interaction Maps/drug effects , Molecular Docking Simulation , DiterpenesABSTRACT
The authors present a narrative that details the cause and process of a woman's transformation from beauty to ugliness in a Japanese tale. In " Tokaido Yotsuya Kaidan ," the metamorphosis from a beauty to an ugly woman is analyzed. After taking medication to recover from childbirth, Oiwa's face became disfigured and grotesque. Oiwa: It seems to be good for my blood, but when I drink it, it causes fraying and breakdown, causing sudden pain. I feel a numbing dullness. When she looked at herself in the mirror, she was shocked. Oiwa: What's wrong with my face? I hate this, it's such a disgusting thing. Neighbor: It was a lie that the medicine you drank was a helpful medicine that protects the appearance of people's faces. Your face is that of a wicked woman (). Oiwa: Is it really me? Why does she have the face of an evil woman? Her hair falls out in a gruesome combing scene, driving her mad. The poison Oiwa took was aconite, which grows wild in Japan. Both aconite tincture and raw aconite roots contain high concentrations of Aconitum alkaloids, which can penetrate the stratum corneum following the diffusion gradient. As her hair fell out during a horrific combing session, she abandoned her maternal role and sought revenge, having lost what she considered a symbol of her femininity. In treating female patients with facial disfigurement, it is important to be mindful of their psychological state, akin to that of Oiwa, who became disfigured through no fault of her own.
Subject(s)
Aconitum , Beauty , Adult , Female , Humans , Aconitum/adverse effects , East Asian People , JapanABSTRACT
The perennial herb Aconitum sinomontanum Nakai (Ranunculaceae) has been utilized as a traditional oriental medicine in China for numerous years. The principal pharmacological constituent of A. sinomontanum, lappaconitine (LA), exhibits analgesic, anti-inflammatory, anti-tumor, anti-arrhythmic, and anti-epileptic activities. Due to its potent efficacy and non-addictive nature, LA is widely utilized in the management of cancer pain and postoperative analgesia. This review encompasses the research advancements pertaining to LA including extraction methods, separation techniques, pharmacological properties, chemical modifications, and clinical applications. Additionally, it offers insights into the potential applications and current challenges associated with LA to facilitate future research endeavors.
Subject(s)
Aconitine , Aconitum , Analgesics , Aconitine/analogs & derivatives , Aconitine/pharmacology , Aconitine/therapeutic use , Humans , Analgesics/therapeutic use , Analgesics/pharmacology , Animals , Aconitum/chemistry , Diterpenes/therapeutic use , Diterpenes/pharmacology , Diterpenes/chemistryABSTRACT
Herbs, such as Aconitum carmichaeli Debeaux (ACD), have long been used as therapies, but it is difficult to identify which organs of the human body are affected by the various compounds. In this study, we predicted the organ where the drug predominantly acts using bioinformatics and verified it using transcriptomics. We constructed a computer-aided brain system network (BSN) and intestinal system network (ISN). We predicted the action points of ACD using network pharmacology (NP) analysis and predicted the dockable proteins acting in the BSN and ISN using statistical-based docking analysis. The predicted results were verified using ACD-induced transcriptome analysis. The predicted results showed that both the NP and docking analyses predominantly acted on the BSN and showed better hit rates in the hub nodes. In addition, we confirmed through verification experiments that the SW1783 cell line had more than 10 times more differentially expressed genes than the HT29 cell line and that the dominant acting organ is the brain, using network dimension spanning analysis. In conclusion, we found that ACD preferentially acts in the brain rather than in the intestine, and this multi-bioinformatics-based approach is expected to be used in future studies of drug efficacy and side effects.
Subject(s)
Aconitum , Computational Biology , Aconitum/chemistry , Humans , Computational Biology/methods , Gene Expression Profiling , Brain/metabolism , Brain/drug effects , Transcriptome/drug effects , Molecular Docking Simulation , Network Pharmacology , Intestines/drug effects , HT29 Cells , Plant Extracts/pharmacology , Plant Extracts/chemistryABSTRACT
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.
Subject(s)
Aconitum , Anti-Bacterial Agents , Antioxidants , Gold , Metal Nanoparticles , Plant Extracts , Silver , Metal Nanoparticles/chemistry , Silver/chemistry , Gold/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Aconitum/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Catalysis , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/chemical synthesis , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Green Chemistry Technology , Escherichia coli/drug effectsABSTRACT
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.
Subject(s)
Aconitum , Alkaloids , Plants, Medicinal , Aconitum/chemistry , Alkaloids/analysis , Polysaccharides/chemistry , China , Plant Roots/chemistryABSTRACT
We have developed a rapid genus identification method for poisonous plants. The real-time PCR using the TaqMan® probe method was employed for detection, with the amplified targets being the "trnL (UAA)-intron" or "trnL-trnF intergenic spacer" regions of chloroplast DNA. The targeted plants were selected six genera (Aconitum, Colchicum, Veratrum, Brugmansia, Scopolia and Narcissus), which have been implicated in many instances of food poisoning in Japan. A tissue lysis solution was used for DNA extraction, which can be completed within approximate 30 min. A master mix corresponding to the tissue lysis solution was used for real-time PCR reagents. As a result, we were able to complete the entire process from DNA extraction to genus identification in 4 to 5 hr. The detection sensitivity was estimated at approximately 1 pg of DNA for all six plant genera. Remarkably, an amplification plot was discerned even with the crude cell lysates of all samples. It was also possible to obtain amplification curves for three plant samples that had been subjected to simulated cooking (boiling). This study suggests that the developed method can rapidly identify six genera of poisonous plants.
Subject(s)
Plants, Toxic , Real-Time Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction/methods , Plants, Toxic/classification , Plants, Toxic/genetics , DNA, Chloroplast/genetics , DNA, Chloroplast/analysis , DNA, Plant/genetics , DNA, Plant/analysis , Veratrum/genetics , Veratrum/chemistry , Veratrum/classification , Aconitum/genetics , Aconitum/classification , Aconitum/chemistry , Sensitivity and Specificity , Time Factors , Foodborne Diseases/prevention & controlABSTRACT
Activated hepatic stellate cells differentiate into myofibroblasts, which synthesize and secrete extracellular matrix (ECM) leading to liver fibrosis. It was previously demonstrated that bulleyaconitine A (BLA), an alkaloid from Aconitum bulleyanum, inhibits proliferation and promotes apoptosis of human hepatic Lieming Xu-2 (LX-2) cells. In this study, we analyzed the effect of BLA on the production of ECM and related proteins by LX-2 cells activated with acetaldehyde (AA). The cells were randomized into the control group, AA group (cells activated with 400 µM AA), and BLA+AA group (cells cultured in the presence of 400 µM AA and 18.75 µg/ml BLA). In the BLA+AA group, the contents of collagens I and III and the expression of α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1) were statistically significantly higher than in the control, but lower than in the AA group. Expression of MMP-1 in the BLA+AA group was also significantly higher than in the AA group, but lower than in the control. Expression of TIMP-1 in the BLA+AA group was significantly higher than in the control, but lower than in the AA group. Thus, BLA suppressed activation and proliferation of LX-2 cells by inhibiting TGF-ß1 signaling pathway and decreasing the content of collagens I and III by reducing the MMP-1/TIMP-1 ratio.