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1.
Plant Signal Behav ; 17(1): 2083818, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35713121

RESUMO

Aconitum carmichaelii Debx. is used as traditional herbal medicine in China, Japan, and other Asian countries. A. carmichaelii has two modes for reproduction: sexual reproduction with seed and vegetative reproduction with vegetative propagules. The vegetative propagules are belowground and invisible. To date, only a handful of studies for the clonal growth are available. In this study, we investigated the clonal growth by anatomical and morphological changes. Results revealed that the axillary bud appeared on the rhizome. Furthermore, the axillary meristem in the axillary bud differentiated a bud upwards and an adventitious root (AR) downwards. The AR expanded to a tuberous root in order to provide the bud nutrients for the new plant. The AR branched LRs. In addition, some lateral roots (LRs) on the AR also swelled. Both the AR and LR were found to follow a similar pattern of development. However, high lignification in the stele region of LRs inhibited further expansion. AR development was attributed to activities of the cambium and meristem cell, starch accumulation, stele lignification, and a polyarch stele. Our study not only provides a better understanding of clonal growth but also provides clues to explore the regulatory mechanisms underlying AR development in A. carmichaelii.


Assuntos
Aconitum , China , Raízes de Plantas
2.
Carbohydr Polym ; 291: 119655, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698356

RESUMO

Roots of Aconitum carmichaelii are used in Asian countries due to its content of bioactive alkaloids. In the production of root preparations, tons of leaves are usually discarded, leading to a huge waste of herbal material. The aim of this study is to investigate the polysaccharides in these unutilized leaves. A neutral polysaccharide (AL-N) appeared to be a mixture of heteromannans, and two purified acidic polysaccharides (AL-I-I and AL-I-II) were shown to be pectins containing a homogalacturonan backbone substituted with terminal ß-Xylp-units. AL-I-I consisted of a type-I rhamnogalacturonan core, with arabinan and type-II arabinogalactan domains while AL-I-II was less branched. AL-N and AL-I-I were able to modulate the complement system, while AL-I-II was inactive. Interestingly, AL-N, AL-I-I and AL-I-II were shown to exert anti-inflammatory effects on porcine enterocyte IPEC-J2 cells. AL-I-I and AL-I-II were able to down-regulate the expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 1 (NOD1).


Assuntos
Aconitum/química , Alcaloides , Polissacarídeos , Alcaloides/análise , Alcaloides/química , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Linhagem Celular , Enterócitos/efeitos dos fármacos , Folhas de Planta/química , Polissacarídeos/análise , Polissacarídeos/química , Polissacarídeos/farmacologia , Suínos
3.
Sci Rep ; 12(1): 9439, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676401

RESUMO

Aconitum episcopale Leveille is an important medicinal plant from the genus Aconitum L. of Ranunculaceae family and has been used as conventional medicine in Bai, Yi, and other ethnic groups of China. According to the available data and Ethno folk applications, A. episcopale is the only Aconitum species that has detoxifying and antialcoholic property. It can detoxify opium, especially the poisoning of Aconitum plants. Aconitum species have been widely used for their medicinal properties, and it is important to be noted that many of the species of this plant are reported to be toxic also. Distinguishing the species of this plant based on the morphology is a tough task and there are also no significant differences in the chemical composition. Therefore, before application of this plant for medicinal usage, it is very important to identify the species which could be life-threatening and exclude them. In this paper, the complete chloroplast (cp) genome sequence of A. episcopale was acquired by Illumina paired-end (PE) sequencing technology and compared with other species in the same family and genus. Herein, we report the complete cp genome of A. episcopale. The whole circular cp genome of A. episcopale has been found to be of 155,827 bp in size and contains a large single-copy region (LSC) of 86,452 bp, a small single-copy region (SSC) of 16,939 bp, and two inverted repeat regions (IRs) of 26,218 bp. The A. episcopale cp genome was found to be comprised of 132 genes, including 85 protein-coding genes (PCGs), 37 transfer RNA genes (tRNAs), eight ribosomal RNA genes (rRNAs), and two pseudogenes. A total of 20 genes contained introns, of which 14 genes contained a single intron and two genes had two introns. The chloroplast genome of A. episcopale contained 64 codons encoding 20 amino acids, with the number of codons encoding corresponding amino acids ranging from 22 to 1068. The Met and Trp amino acids have only one codon, and other amino acids had 2-6 codons. A total of 64 simple sequence repeats (SSRs) were identified, among which mononucleotide sequences accounted for the most. Phylogenetic analysis showed that A. episcopale is closely related with A. delavayi. Cumulatively the results of this study provided an essential theoretical basis for the molecular identification and phylogeny of A. episcopale.


Assuntos
Aconitum , Genoma de Cloroplastos , Aconitum/genética , Aminoácidos/genética , Códon , Filogenia , RNA de Transferência/genética
5.
Biomed Pharmacother ; 151: 113115, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35605296

RESUMO

Aconitine is a diterpenoid alkaloid, which mainly exists in the plants of Aconitum. In the last decade, a plethora of studies on the pharmacological activities of aconitine has been conducted and demonstrated that aconitine possessed an extensive range of pharmacological activities such as anti-tumor, anti-inflammatory, analgesic, local anesthesia, and immunomodulatory effects. Pharmacokinetic studies indicated that aconitine may have the characteristics of poor bioavailability, wide distribution, and slow elimination. However, studies have also found that aconitine has toxic effects on the heart, nerves, embryos, etc. Therefore, we believe that aconitine may not be suitable for heart patients and pregnant women to treat related diseases. It is important to note that all of these pharmacological effects require further high-quality studies to determine the clinical efficacy of aconitine. This review aims to summarize the advances in pharmacological, pharmacokinetics, toxicity, and detoxification of aconitine in the last decade with an emphasis on its anti-tumor and anti-inflammatory activities, to provide researchers with the latest information and point out the limitations of relevant research at the current stage and the aspects that should be strengthened in future research.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Aconitina/farmacocinética , Aconitina/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Gravidez
6.
Food Chem ; 391: 133234, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35605540

RESUMO

The dual functions of phytotoxin, such as aconitine, with biological activity and toxicity ignited the related food poisoning intentionally or accidentally from time to time. The fast and accurate qualitative analysis is a prerequisite for tracking the source of poisoning and taking correct treatments. Taking the single molecule level sensitivity and molecular fingerprinting of Surface-enhanced Raman spectroscopy (SERS), we developed a highly sensitive and accurate strategy for the trace detection of three structurally similar aconitines (ATs) (aconitine, mesaconitine and hypoaconitine) by employing the 100 nm Ag NPs colloid as the SERS substrate. It was figured out that the lowest detectable concentration is in the level of 5.0 µg/L for these three ATs with the linear range of 5.0-100.0 µg/L. The qualitative and quantitative analysis of trace ATs spiked in various food samples was realized in 3 mins, which demonstrated the SERS based strategy is very promising towards the fast and on-site detection of ATs in the field of food safety or criminal identification.


Assuntos
Aconitum , Nanopartículas Metálicas , Aconitina , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos
7.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2509-2515, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35531698

RESUMO

A high-throughput screening machine learning model for mitochondrial function was constructed, and compounds of Aco-niti Lateralis Radix Praeparata were predicted. Deoxyaconitine with the highest score and benzoylmesaconine with the lowest score among the compounds screened by the model were selected for mitochondrial mechanism analysis. Mitochondrial function data were collected from PubChem and Tox21 databases. Random forest and gradient boosted decision tree algorithms were separately used for mo-deling, and ECFP4(extended connectivity fingerprint, up to four bonds) and Mordred descriptors were employed for training, respectively. Cross-validation test was carried out, and balanced accuracy(BA) and overall accuracy were determined to evaluate the performance of different combinations of models and obtain the optimal algorithm and hyperparameters for modeling. The data of Aconiti Lateralis Radix Praeparata compounds in TCMSP database were collected, and after prediction and screening by the constructed high-throughput screening machine learning model, deoxyaconitine and benzoylmesaconine were selected to measure mitochondrial membrane potential, reactive oxygen species(ROS) level and protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax) and peroxisome proliferator-activated receptor-γ-coactivator 1α(PGC-1α). The results showed that the model constructed using gradient boosted decision tree+Mordred algorithm performed better, with a cross-validation BA of 0.825 and a test set accuracy of 0.811. Deoxyaconitine and benzoylmesaconine changed the ROS level(P<0.001), mitochondrial membrane potential(P<0.001), and protein expression of Bcl-2(P<0.001, P<0.01) and Bax(P<0.001), and deoxyaconitine increased the expression of PGC-1α protein(P<0.01). The high-throughput screening model for mitochondrial function constructed by gradient boosted decision tree+Mordred algorithm was more accurate than that by random forest+ECFP4 algorithm, which could be used to build an algorithm model for subsequent research. Deoxyaconitine and benzoylmesaconine affected mitochondrial function. However, deoxyaconitine with higher score also affected mitochondrial biosynthesis by regulating PGC-1α protein.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Aconitum/química , Algoritmos , Medicamentos de Ervas Chinesas/química , Ensaios de Triagem em Larga Escala , Aprendizado de Máquina , Mitocôndrias , Espécies Reativas de Oxigênio , Proteína X Associada a bcl-2
8.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1904-1912, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534261

RESUMO

This study selected three typical Chinese herbs with cold property(Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma) and another three with heat property(Cinnamomi Cortex, Zingiberris Rhizoma, and Aconiti Lateralis Radix Praeparata) to observe their regulatory effects on metabolism in animal organism, especially on lipid and energy metabolism in mice after a short-(7 d) and long-term(35 d) intervention. The mRNA expression levels of lipid metabolism genes in epididymal adipose tissue and liver were determined by real-time PCR. The oxygen consumption, carbon dioxide production, and energy consumption were detected by metabolic system. After the short-term intervention, the Chinese herbs with heat property significantly reduced epididymal adipose tissue index and elevated the expression levels of acetyl-CoA carboxylase(ACC), lipoprotein lipase(LPL), and carnitine-palmityl transferase 1(CPT-1) in liver and epididymal adipose tissues. However, those with cold property promoted the expression of above-mentioned genes in epididymal adipose tissue. After the long-term intervention, cold and heat Chinese herbs had no significant effect on epididymal adipose tissue index of animals, while cold Chinese herbs could increase carbon dioxide production and energy consumption and reduce activity. These findings demonstrated that the short-term intervention effects of cold and heat Chinese herbs on animal metabolism were significantly stronger than the long-term intervention effects. Specifically, the short-term intervention with cold Chinese herbs enhanced the lipid metabolism in epididymal adipose tissue, while the heat Chinese herbs promoted lipid metabolism in epididymal adipose tissue and liver. The long-term intervention with cold and heat Chinese herbs resulted in no obvious change in lipid level, but long-term intervention with cold Chinese herbs accelerated energy consumption of the body. This study preliminarily observed the effects of cold and heat Chinese herbs on normal animal physiology from lipid and energy metabolism, which would provide reference for explaining the biological basis of Chinese herbs with cold or heat property based on biological response.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Animais , Dióxido de Carbono , China , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético , Temperatura Alta , Lipídeos , Camundongos
9.
Ecotoxicol Environ Saf ; 237: 113539, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489139

RESUMO

Aconitum genus generally contains hypertoxic alkaloids. Poisoning incidents due to the improper ingestion of Aconitum materials frequently occur around the world. DNA barcoding is considered as a powerful tool for species identification, but complete sequences of conventional DNA barcodes are sometimes unattainable from food and highly processed products due to severe DNA degradation. Therefore, a shorter molecular marker will be more profitable for the authentication and poisoning diagnosis of Aconitum materials. In this study, 1246 psbA-trnH sequences and chloroplast genomes representing 183 taxa of Aconitum were collected, and a 23-bp nucleotide signature unique to Aconitum genus (5'-TATATGAGTCATTGAAGTTGCAG-3') was developed. The nucleotide signature was conserved and universal within Aconitum while divergent among other genera. The specific molecular signature was then successfully applied to the detection of processed Aconitum ingredients. To further evaluate the application potential of nucleotide signature in completely unknown mixture samples, boiled food mixtures, containing different ratios of Aconitum materials, were sequenced by high-throughput sequencing technology. The results showed that the nucleotide signature sequence could be directly extracted from raw sequencing data, even at a low DNA concentration of 0.2 ng/µl. Consequently, the 23-bp genus-specific nucleotide signature represents a significant step forward in the use of DNA barcoding to identify processed samples and food mixtures with degraded DNA. This study undoubtedly provides a new perspective and strong support for the identification and detection of Aconitum-containing products, which can be further introduced to the diagnosis of food poisoning.


Assuntos
Aconitum , Alcaloides , Genoma de Cloroplastos , Aconitum/genética , Sequenciamento de Nucleotídeos em Larga Escala , Nucleotídeos
10.
MMWR Morb Mortal Wkly Rep ; 71(16): 569-573, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35446826

RESUMO

On May 3, 2018, Chongqing Center for Disease Control and Prevention (CQCDC) received a report of 15 persons with numbness of the tongue or limbs and vomiting of unknown etiology; all ill persons had attended an adult birthday luncheon in Bishan District, Chongqing municipality, in southwest China. Initial reports indicated that one person had died. Within 2 hours, CQCDC and Western Chinese Field Epidemiology Training Program staff members launched an investigation that included identification of cases, laboratory testing of drinks, and patient interviews to identify the cause of what appeared to be a poisoning. Among the 15 cases, five persons died. The investigation of this apparent mass intoxication implicated a homemade alcoholic beverage produced from a highly toxic flowering plant in the genus Aconitum used in traditional Chinese medicine. Although the risk of aconite toxicity is known, approximately 5,000 cases of aconite poisoning incidents were reported in China, Germany, Japan, and other countries during 1993-2005; most cases of fatal poisoning occurred in China (1). This event highlights the importance of enforcing and complying with existing regulations regarding sale and purchase of Aconitum species (also known as wolfbane), and of dissemination of critical public health messages.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Envenenamento , Adulto , Bebidas Alcoólicas , China/epidemiologia , Humanos , Japão
11.
J Ethnopharmacol ; 293: 115270, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405250

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitine, a C19-norditerpenoid alkaloid, derives from many medicinal plants such as Aconitum carmichaelii Debx. (Chinese:), Aconitum kusnezoffii Reichb (Chinese:), which were used to rheumatic fever, painful joints and some endocrinal disorders. AIMS OF THE REVIEW: The present paper reviews research progress relating to the pharmacokinetics, physiological and pathological processes of aconitine, while some promising research direction and the detoxification of aconitine are also discussed. MATERIALS AND METHODS: The accessible literature on aconitine, from 1990 to 2020, obtained from published materials of electronic databases, such as SCI finder, PubMed, Web of Science, Science Direct, Springer and Google Scholar was systematically analyzed. RESULTS: In this review, we address the pharmacokinetics of aconitine, as well as its pharmacological effects including anti-cancer, anti-inflammatory, anti-virus, immunoregulation, analgesic, insecticide and inhibition of androgen synthesis. Further, we summarize the toxicity of aconitine such as cardiotoxicity and neurotoxicity, on which we strikingly focus on the ways to reduce the toxicity of aconitine based. CONCLUSIONS: Aconitine plays an vital role in a wide range of physiological and pathological processes and we can reduce the toxicity of aconitine by compatibility and hydrolysis. Although some issues still exist, such as the correlative relationship between the dose and toxicity of aconitine not being clear, our review may provide new ideas for the application of aconitine in the treatment of related diseases.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Plantas Medicinais , Aconitina/farmacocinética , Aconitina/toxicidade , Anti-Inflamatórios , Medicamentos de Ervas Chinesas/farmacologia
12.
J Ethnopharmacol ; 293: 115317, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35469829

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a folk medicine, Aconitum sinomontanum Nakai (Ranunculaceae) a perennial herbaceous flowering plant, is a widely used traditional Chinese medicine. Its rhizomes and roots are known as 'Gaowutou' in China, and it has been traditionally used for the treatment of rheumatoid arthritis, painful swelling of joints, bruises and injuries and has been known to grow well in regions of high altitude such as Gansu, Tibet etc. THE AIM OF THE REVIEW: This systematic review the comprehensive knowledge of the A. sinomontanum, including its traditional processing and uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and its use in clinical settings to emphasize the benefits of this species. We also discuss expectations for prospective research and implementation of this herb. This work lays a solid foundation for further development of A. sinomontanum. MATERIALS AND METHOD: Information on the studies of A. sinomontanum was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters dissertation. RESULTS: As a member of the Ranunculaceae family, A. sinomontanum possesses its up-and-coming biological characteristics. It is widely reported for treating rheumatoid arthritis, painful swelling of joints, bruises and injuries. Currently, over 71 phytochemical ingredients have been obtained and identified from different parts of A. sinomontanum. Among them, alkaloids, flavonoids, steroids, glycosides are the major bioactive constituents. Activities such as antinociceptive, anti-inflammatory, antitumor, antiarrhythmic, local anesthetic, antipyretic, antimicrobial, insecticidal and others have been corroborated in vivo and in vitro. These properties are attributed to different alkaloids. In addition, many of the active ingredients, such as lappaconitine, ranaconitine and total alkaloids have been used as quality markers. CONCLUSION: This work contributes to update the ethnopharmacological uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and clinical settings information for A. sinomontanum, which provide basic information to help better understand the pharmacological and toxicological activities of A. sinomontanum in human. However, further in-depth studies are needed to determine the medical uses of this herb and its chemical constituents, pharmacological activities, clinical applications and toxicology.


Assuntos
Aconitum , Alcaloides , Artrite Reumatoide , Contusões , Ranunculaceae , Aconitum/química , Artrite Reumatoide/tratamento farmacológico , Contusões/tratamento farmacológico , Etnofarmacologia , Humanos , Medicina Tradicional Chinesa , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Estudos Prospectivos
13.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1215-1221, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35343147

RESUMO

In Hezhang county, Guizhou province, black spot tends to occur to Aconitum carmichaelii in the hot rainy summer, with the incidence up to 50%-70%, seriously impacting the yield and quality of the medicinal material. Thus, this study aims to clarify the pathogen and the occurrence characteristics. To be specific, the pathogen was isolated and identified according to Koch's postulates and the pathogenicity and biological characteristics were determined. In addition, the sensitivity of the pathogen to four microbial fungicides, four botanical fungicides, and five chemical fungicides was determined with the mycelium growth rate method for the purpose of screening out optimal fungicides. The pathogen was identified as Alternaria alternate, as evidenced by the similar colony morphology and microscopic characteristics and 99.55%-100% similarity in sequences of rDNA-ITS, LSU, 18S, and TEF of the two. The optimum growth conditions for A. alternata were 28 ℃, pH 8, and continuous darkness. Bacillus subtilis had strong inhibitory effect on the pathogen, and the inhibition rate was more than 90% when the concentration was 1 mg·L~(-1). In addition, difenoconazole and quinoline copper can also control the pathogen, with median effective concentration(EC_(50)) of 2.92 and 9.02 mg·L~(-1), respectively. This study lays a theoretical basis for the field control of black spot in A. carmichaelii.


Assuntos
Aconitum , Fungicidas Industriais , Alternaria , Fungicidas Industriais/farmacologia , Micélio
14.
BMC Microbiol ; 22(1): 70, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264111

RESUMO

BACKGROUND: The plant microbiome is vital for plant health, fitness, and productivity. Interestingly, plant metabolites and the plant microbiome can influence each other. The combination of metabolomics and microbiome may reveal the critical links between the plant and its microbiome. It is of great significance to agricultural production and human health, especially for Chinese medicine research. Aconitum vilmorinianum Kom. is a herb with alkaloid activities, and its roots are the raw material for some Chinese medicines. Former studies have investigated alkaloidal metabolites and antibacterial activities of endophytes in A. vilmorinianum roots. However, there are limited reports on the root microbiota that can influence the alkaloidal metabolome of A. vilmorinianum. RESULTS: This research used ultra performance liquid chromatography-tandem mass spectrometry technology and high-throughput sequencing to examine the alkaloidal metabolome, bacterial microbiota, and fungal microbiota in A. vilmorinianum roots at two different sites in China. The results revealed that the samples from the two sites were rich in distinct alkaloidal metabolites and recruited significantly different root microbiota. Based on bioinformatics analysis, we found the potential bacterial and fungal microbiota impacting the alkaloidal metabolome in A. vilmorinianum. CONCLUSION: Our findings reveal the composition of the alkaloidal metabolome, bacterial root microbiota, and fungal root microbiota in A. vilmorinianum roots at two different sites. Potential root microbiota that can influence the alkaloidal metabolome of A. vilmorinianum are indicated. This study provides a strategy for the cultivation and research of A. vilmorinianum and other Chinese herbs.


Assuntos
Aconitum , Alcaloides , Microbiota , Aconitum/química , Bactérias/genética , Humanos , Metaboloma , Metabolômica/métodos
15.
J Ethnopharmacol ; 292: 115216, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35331875

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy. AIM OF THE STUDY: This review aims to document and summarize critical and comprehensive information about traditional uses, phytochemistry, pharmacology, toxicology and processing methods of Tiebangchui. Perspectives for possible future investigations have been discussed. MATERIALS AND METHODS: Relevant information about Tiebangchui (A. pendulum and A. flavum) was collected from internationally recognized electronic scientific databases, such as Web of Science, PubMed, Science Direct, Springer Link, ACS, and CNKI. Then, classic Tibetan medical books, such as Four Medical Tantra, and Jing Zhu Materia Medica, and official drug standards were reviewed. RESULTS: A total of 95 chemical constituents have been isolated and identified from Tiebangchui, and most of them were diterpenoid alkaloids. These phytochemicals showed a wide range of pharmacological properties, such as anti-inflammation, anti-rheumatoid arthritis, analgesic, local anesthetic, anti-cancer and anti-bacterial activities. Hence, Tiebangchui is broadly used in hundreds of preparations to treat fever, arthritis, rheumatic arthralgia, traumatic injury, furuncle and swelling. Cardiotoxicity, neurotoxicity and gastrointestinal toxicity are the main toxic effects caused by the Aconitum alkaloids of Tiebangchui. Various processing methods, including steaming, decocting and sand-frying, and traditional Tibetan medicine processing methods, such as processing with Hezi decoction, Qingke wine and Zanba, are effective in attenuating toxicity while retaining efficacy. CONCLUSIONS: The present review provides primary information of Tiebangchui, particularly for its traditional uses, botanical characteristics, phytochemicals, outstanding bioactivities and processing methods. However, studies that explored the in vivo pharmacokinetics and mechanism of Tiebangchui, as well as its quality markers, qualitative and quantitative analysis are still insufficient. Processing methods that attenuate toxicities, evaluations of efficacy, in vivo processes and biological effects, the mechanisms of processed products should be further explored.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Aconitum/química , Alcaloides/análise , Medicamentos de Ervas Chinesas/farmacologia , Etnofarmacologia/métodos , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/farmacologia , Raízes de Plantas/química
16.
Phytomedicine ; 100: 154059, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35338992

RESUMO

BACKGROUND: The synergic action of compound prescriptions is an important feature and core advantage of traditional medicine. Ginseng-Fuzi decoction is a classic compatible phytomedicine in China, of which Ginseng can effectively reduce the toxicity of Fuzi in clinical, but the detoxification chemical mechanism is still unclear. PURPOSE: Develop a novel method for real-time tracking and monitoring of complex substances in the decoction system of traditional Chinese medicine to uncover the detoxification effect Ginseng on Fuzi and explore the possible chemical reaction mechanism of Ginseng-Fuzi co-decoction. METHODS: A novel real-time monitoring system, online filtration electrospray ionization mass spectrometry, was developed for extremely complex substances analysis in the decoction of traditional medicine compounds to uncover the directionally detoxification effect and the mechanism of compatibility interaction. RESULTS: Nine key alkaloids and 7 ginsenosides in Ginseng-Fuzi decoction were simultaneously in-situ monitoring in positive ion mode or negative ion mode respectively. Both types of targeted analytes had satisfactory MS signal response for real-time qualitative and quantitative analysis with high precision (RSD < 14.04%) and low LLODs (0.002 ng/ml-10 ng/ml). Through long-term tracking analysis, the exact detoxification and synergistic effect of Ginseng-Fuzi decoction were confirmed as the concentration of main toxic alkaloids decreased (e.g. the content of mesaconitine has been reduced by about 38%) and the main active monoester alkaloids increased obviously. More importantly, the possible molecular mechanism of the detoxification effect of Ginseng compatibility was revealed for the first time, which was the nucleophilic substitution reaction of diester alkaloids catalyzed by fatty acids. CONCLUSION: This study revealed the exact effect of co-decoction of Ginseng and Fuzi at the molecular level and the chemical reaction mechanism of fatty acid-catalyzed degradation of toxic diester-type alkaloids. The comprehensive multi-component real-time monitoring strategy for complex traditional medicine compounds developed and implemented here has important demonstration significance for revealing the scientific connotation of the compatibility of compound traditional medicine.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Panax , Aconitum/química , Alcaloides/química , Cromatografia Líquida de Alta Pressão/métodos , Diterpenos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas por Ionização por Electrospray/métodos
17.
J Nat Med ; 76(3): 594-604, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35178660

RESUMO

Processed aconite root (PA), the tuberous root of Aconitum carmichaelii prepared by autoclaving, is a crude drug used in Japanese traditional Kampo medicine and traditional Chinese medicine for the symptoms of kidney deficiency, that is related to the muscle atrophy in modern medicine. The objective of the present study is to evaluate the effectiveness of PA on muscle atrophy and to find its active ingredients using dexamethasone-induced muscle ring finger protein-1 (MuRF1) mRNA expression in murine myoblast C2C12 cells. Dexamethasone-induced MuRF1 expression was significantly suppressed by methanol-soluble part of boiling water extract of PA in a concentration-dependent manner with its IC50 value of 1.5 mg/ml. By the activity-guided fractionations of PA extract using the partition between organic solvents and its aqueous solution, the activity of PA did not transfer into the fraction containing aconitine-type diterpenoid alkaloids but into BuOH layer. Then, we found higenamine and salsolinol as the active ingredients in PA. Higenamine and salsolinol significantly suppressed dexamethasone-induced MuRF1 expression, and their IC50 values were 0.49 and 50 µM, respectively. The contents of higenamine and salsolinol in the decoctions of commercially available fourteen PA products are 0.12 and 14 µg/ml as the average values, and varied with the coefficient of variation (CV) values of 97 and 63%, respectively. Higenamine also significantly suppressed dexamethasone-induced mRNA expressions of muscle atrophy F-box protein (MAFbx)/atrogin1, casitas B-lineage lymphoma-b (Cbl-b), troponin, branched-chain amino acid aminotransferase 2 (BCAT2), and Bcl-2 binding and pro-apoptotic protein3 (Bnip3). Although the quality control of PA is regulated by the contents of diterpene alkaloids, salsolinol and higenamine can be used as the marker compounds to certificate the pharmacological activities of PA.


Assuntos
Aconitum , Aconitum/química , Animais , Dexametasona/efeitos adversos , Camundongos , Músculos/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , RNA Mensageiro
18.
J Integr Med ; 20(2): 104-113, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34996731

RESUMO

Aconitum heterophyllum (Patrees) is a critically endangered medicinal herb of the northwestern Himalayas and has enormous pharmacological potential. It is the only nonpoisonous member of the genus Aconitum, and has been used as a medicinal herb since ancient times. A. heterophyllum is an important ingredient in many traditional systems of medicine. Mostly, it is harvested for its roots, and its medicinal properties are due to the presence of diverse bioactive secondary metabolites, commonly known as aconites. Our understanding of the pharmacological properties of this intriguing genus is continuously growing due to its broad chemical diversity. The therapeutic uses identified by traditional medicinal practice are receiving extensive study. Multiple in vitro experimental investigations of A. heterophyllum have reported the analgesic, anti-inflammatory, antiarrhythmic, antiparasitic and anticancer properties, as well as its effects on the central nervous system. In this review, we highlight the classification, distribution, commerce, traditional uses, phytochemistry, pharmacology and conservation measures relevant to this species. Additionally, this review includes the biosynthetic pathways of A. heterophyllum's key constituents, which could be targeted to enhance the expression levels of desired metabolites via genetic interventions. Studying the genomics, transcriptomics, proteomics and metabolomic aspects of this species would be helpful in developing highly designed genotypes and chemotypes of this species to be used in commercial production.


Assuntos
Aconitum , Plantas Medicinais , Aconitum/química , Aconitum/genética , Etnofarmacologia , Extratos Vegetais/química , Raízes de Plantas/química , Plantas Medicinais/química
19.
Naunyn Schmiedebergs Arch Pharmacol ; 395(1): 65-76, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34727218

RESUMO

Aconitine linoleate (1) is a lipo-diterpenoid alkaloid, isolated from Aconitum sinchiangense W. T. Wang. The study aimed at investigating the anti-proliferative efficacy and the underlying mechanisms of 1 against MCF-7 and MCF-7/ADR cells, as well as obvious the safety evaluation in vivo. The cytotoxic activities of 1 were measured in vitro. Also, we investigated the latent mechanism of 1 by cell cycle analysis in MCF-7/ADR cells and topo I and topo IIα inhibition assay. Molecular docking is done by Discovery Studio 3.5 and Autodock vina 1.1.2. Finally, the acute toxicity of 1 was detected on mice. 1 exhibited significant antitumor activity against both MCF-7 and MCF-7/ADR cells, with IC50 values of 7.58 and 7.02 µM, which is 2.38 times and 5.05 times more active, respectively than etoposide in both cell lines, and being 9.63 times more active than Adriamycin in MCF-7/ADR cell lines. The molecular docking and the topo inhibition test found that it is a selective inhibitor of topoisomerase IIα. Moreover, activation of the damage response pathway of the DNA leads to cell cycle arrest at the G0G1 phase. Furthermore, the in vivo acute toxicity of 1 in mice displayed lower toxicity than aconitine, with LD50 of 2.2 × 105 nmol/kg and only slight pathological changes in liver and lung tissue, 489 times safer than aconitine. In conclusion, compared with aconitine, 1 has more significant anti-proliferative activity against MCF-7 and MCF-7/ADR cells and greatly reduces in vivo toxicity, which suggests this kind of lipo-alkaloids is powerful and promising antitumor compounds for breast cancer.


Assuntos
Aconitina/farmacologia , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Aconitina/administração & dosagem , Aconitina/toxicidade , Aconitum/química , Animais , Animais não Endogâmicos , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo II , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Concentração Inibidora 50 , Ácido Linoleico/química , Células MCF-7 , Masculino , Camundongos , Simulação de Acoplamento Molecular , Células NIH 3T3 , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores
20.
J Sep Sci ; 45(3): 739-751, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34865311

RESUMO

Trace amounts of components in traditional Chinese medicine are considered pharmacological active substances used for treating many serious diseases. However, purifying all the trace substances and making clear their structures are not easy. In this context, high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., which led to the identification of 33 nodes in different groups (N1-N33). Based on the excremental fragmentation pathway of known diterpenoid alkaloids (1-9) and comparisons of characteristic ions and characteristic loss of analogs in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation of unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex systems caused by trace active compounds.


Assuntos
Aconitum , Alcaloides , Diterpenos , Medicamentos de Ervas Chinesas , Aconitum/química , Alcaloides/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Diterpenos/análise , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas em Tandem
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