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1.
Phytomedicine ; 85: 153522, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33799223

RESUMO

BACKGROUND: Thousands of years of clinical application of Wutou decoction (WTD) support its reliable efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying molecular mechanism remains unclear, and the synergistic involvement of assistant herbs in WTD in enhancing the sovereign herb in treating RA is unknown. PURPOSE: This study aimed to investigate the efficacy-oriented compatibility of five herbs in WTD and the underlying mechanisms. METHODS: The anti-arthritic effects of WTD and the compatibilities of the five herbs in WTD were studied in vivo with adjuvant-induced arthritis (AIA) rat model and in vitro with LPS-induced RAW264.7 macrophage. Network pharmacology analysis was conducted to identify the dominant pathways involved in the anti-arthritis mechanisms of WTD and how the five herbs work synergistically. The results were further verified by in vivo and in vitro experiments. RESULTS: Our data revealed that the five herbs in WTD exert synergistic anti-arthritic effects on RA. Moreover, Radix Aconite (AC) is the principal anti-inflammatory component in WTD according to the extent of therapeutic effects exerted on the AIA rats. In vivo and in vitro experiments demonstrated that WTD inhibited NF-κB phosphorylation and simultaneously increased the expression of Nrf2, which were the major pathways identified by the network pharmacology analysis. The major assistant component, Herba Ephedrae (EP), evidently inhibited NF-κB mediated inflammatory response. The other assistant component, Radix Astragali (AS), considerably enhanced the expression of Nrf2 when used alone or in combination with AC. These combinations improved the anti-arthritis effects on the AIA rats better than that of AC alone. Nevertheless, WTD always achieved the best effects than any combinations both in vivo and in vitro. CONCLUSION: The ministerial herbs EP and AS intensify the anti-arthritic effects of AC by regulating the NF-κB-mediated inflammatory pathway and the Nrf2-mediated anti-oxidation pathway which are the major pathways of WTD for alleviating the symptoms of RA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Aconitum/química , Animais , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fosforilação , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Células THP-1
2.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1564-1573, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787155

RESUMO

Sichuan province is very famous for its abundant resources of traditional Chinese medicine(TCM).However, within the scope of administrative division of Sichuan province, the origin records of Dao-di herbs in different historical periods show a dynamic distribution process. On the basis of carefully sorting out the geographical scope of Sichuan province in different historical periods, this article focuses on the textual research of the Dao-di herbs in Sichuan province recorded in the seven mainstream ancient works of materia medica.The results showed that, according to the records of Mingyi bielu and Bencaojing Jizhu, the main distribution areas of Dao-di herbs were mainly in the central and eastern regions of Sichuan province, mainly including Moschus, Coptidis Rhizoma, Zingiberis Rhizoma, Aconiti Lateralis Radix Praeparata and most of the rest materia medica had become unused in the historical process. Qianjin Yifang records that the distribution areas of Dao-di herbs were mainly in the middle and eastern part of Sichuan province.Aconiti Radix, Lateralis Radix Praeparata, Zingiberis Rhizoma, Notopterygii Rhizoma et Radix are still the Dao-di herbs of Sichuan province. According to the book of Bencao Tujing,the main distribution areas of Dao-di herbs are Chengdu Plain, Yibin and Santai, While Toosendan Fructus, Chuanxiong Rhizoma, Zanthoxyli Pericarpium, Aconiti Radix are still the Dao-di herbs of Sichuan province. Ben Cao Gang Mu records the place of origin as Sichuan.Coptidis Rhizoma, Toosendan Fructus, Cyathulae Radix are still the Dao-di herbs of Sichuan pro-vince. Yaowu Chuchanbian and Zengding Weiyao Tiaobian records the place of origin as Sichuan, as well as Kangding, Songpan, Dujiang-yan, Jiangyou, Nanchong, Ya'an, etc. Moschus, Coptidis Rhizoma, Eucommiae Cortex, Phellodendri Chinensis Cortex are still the Dao-di herbs of Sichuan province. The results of this article provide a new understanding of the history and distribution changes of Dao-di herbs in Sichuan province, and can help to further understand the formation connotation of Sichuan Dao-di herbs.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Materia Medica , Medicina Tradicional Chinesa , Rizoma
3.
Arch Virol ; 166(5): 1513-1515, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33686515

RESUMO

A novel virus was identified in aconite (Aconitum carmichaelii Debx.) in China by high-throughput sequencing (HTS) and tentatively named "aconite virus A" (AcVA). The genomic RNA of AcVA consists of 8,844 nucleotides, excluding the poly(A) at the 3' end. Analysis of the genomic organization of AcVA indicated that it possesses a genomic structure that is typical of carlaviruses and contains six putative open reading frames (ORFs). Pairwise analysis revealed that the replicase and coat protein of AcVA share the highest amino acid sequence identity (43.78% and 57.01%) with those of coleus vein necrosis virus (CVNV) and butterbur mosaic virus (ButMV), respectively. Based on the current classification criteria for carlaviruses, AcVA should be considered a distinct member of the genus Carlavirus.


Assuntos
Aconitum/virologia , Carlavirus/genética , Genoma Viral/genética , Sequência de Aminoácidos , Sequência de Bases , Carlavirus/classificação , China , Fases de Leitura Aberta , Filogenia , Doenças das Plantas/virologia , Plantas Medicinais/virologia , RNA Viral/genética , Proteínas Virais/genética
4.
Fitoterapia ; 149: 104822, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387644

RESUMO

Fuzi, a well-known traditional Chinese medicine developed from the lateral roots of Aconitum carmichaelii Debx., has been widely used for the treatment of heart failure. In order to search for active compounds from Fuzi, a phytochemical study was performed, which resulted in the isolation of 14 aminoalcohol-diterpenoid alkaloids, including one new compound (1). Their cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells were evaluated. All of the alkaloids showed cardioprotective effects in a nonmonotonic concentration-response manner, with the maximum protection rates ranging from 17.96 ± 2.93% to 98.31 ± 0.35%. Compound 5 exhibited the most potent cardioprotective activity. Taking the maximum protection rate as an indicator, the preliminary structure-activity relationship analysis indicated that the substitutions of C-1, C-13, C-15, C-16, and N and the configurations of OMe-6 and OH-15 are important structural features for the cardioprotective activities of the aminoalcohol-diterpenoid alkaloids.


Assuntos
Aconitum/química , Alcaloides/farmacologia , Cardiotônicos/farmacologia , Diterpenos/farmacologia , Alcaloides/isolamento & purificação , Cardiotônicos/isolamento & purificação , Linhagem Celular , China , Diterpenos/isolamento & purificação , Doxorrubicina/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química
5.
Xenobiotica ; 51(3): 345-354, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33332226

RESUMO

Abstracts Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with Cmax and AUC0-∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The Cmax and AUC0-∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.


Assuntos
Aconitum/química , Alcaloides/farmacocinética , Diterpenos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Ratos , Espectrometria de Massas em Tandem
6.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5567-5575, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350220

RESUMO

As a most important Chinese materia medica, Aconiti Lateralis Radix Praeparata(Fuzi) had been widely used in China for thousands of years. This herbalogical study was systematically performed based on variation characteristics of the naming, habitat, harvesting, processing and properties. The sharp toxicity of Fuzi had been well known since the spring and autumn period in the history, which was much earlier than that its medical properties was understood and applied. Sichuan province was regarded as the geo-authentic region of Fuzi all along, where the best quality goods could be provided for clinic use. The study showed the harvesting time of Fuzi was changing in different periods, and the possible effects were of climate change and artificial planting. The perishable characteris-tics of Fuzi severely limited its storage period; therefore, different kinds of storage methods were effectively used since Tang Dynasty. For thousands of years, Fuzi had been processed with various accessories to reduce toxicity, while simultaneously the study on processing mechanism was on going all the time. Fuzi was widely used in clinical practice to cure Yang depletion syndrome, which was based on its function of enhancing Yang and removing cold. Along with the further study on quality evaluation standard, Fuzi will probably get a much wider range of applications.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , China , Medicamentos de Ervas Chinesas/toxicidade , Extratos Vegetais
7.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3961-3966, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893595

RESUMO

The enzymes CYP1 A2 and CYP3 A4 were measured by building a "Cocktail" probe drug and the incubation system of liver microsomes. The compatibility of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix on CYP450 enzyme protein and gene expression was explored from the level of protein and molecular biology. It explored the molecular mechanism of compatibility detoxication of Aconiti Lateralis Radix Praeparata to provide scientific support for clinical safe and effective application of Aconiti Lateralis Radix Praeparata. The CYP450 enzyme activity was determined by using "Cocktail" probe drugs. The content of CYP450 enzyme was measured by CO reduction of differential spectrum method. The mRNA expression of CYP1 A2 and CYP3 A4 enzyme was detected by RT-PCR technology. Compared with the blank group, the CYP1 A2 and CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group with significant differences(P<0.05), while the CYP3 A4 enzyme activity and mRNA expression were no influence in the Aconiti Lateralis Radix Praeparata group. The CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The content of CYP450 enzyme was decreased in the Aconiti Lateralis Radix Praeparata group, contributed to extremely significant difference(P<0.01). The content of CYP450 enzyme was increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The CYP1 A2 and CYP3 A4 enzyme activity and gene expression were enhanced after dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata. The metabolism of toxic ingredients of Aconiti Lateralis Radix Praeparata was accelerated to reach an effect of detoxication. The detoxication mechanism of compatibility of Aconiti Lateralis Radix Praeparata was verified from the viewpoint of liver metabolic enzymes.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Fígado
8.
Phytochemistry ; 178: 112459, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32888673

RESUMO

Nine unprecedented diterpenoid alkaloid, including a diterpenoid alkaloid featuring a diterpenoid moiety, anthoroidine A; one bisditerpenoid alkaloid joined with a carbon-carbon single bond, anthoroidine B; three racemulosine-type C20-diterpenoid alkaloids, anthoroidines C-E; one hetidine-type C20-diterpenoid alkaloid, anthoroidine F; and three hetisine-type C20-diterpenoid alkaloids, anthoroidines G-I, together with ten known diterpenoid alkaloids were isolated from Aconitum anthoroideum DC. Their structures were established via detailed spectroscopic analyses. Most of the isolated compounds along with five known diterpenoid alkaloids obtained in a previous study were screened for neuroprotective activities and acetylcholinesterase inhibitory effects. Nominine showed potent protective activity against MPP+-induced apoptosis in SH-SY5Y cells, with a rescue rate of 34.4% (50 µM). Rotundifosine F showed a significant inhibitory activity against AChE (IC50 = 0.3 µM). The structure-activity relationship of these alkaloids is also briefly discussed.


Assuntos
Aconitum , Alcaloides , Diterpenos , Acetilcolinesterase , Apoptose , Estrutura Molecular , Raízes de Plantas
9.
Ecotoxicol Environ Saf ; 205: 111342, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971455

RESUMO

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.


Assuntos
Aconitum/química , Alcaloides/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/toxicidade , Modelos Biológicos , Alcaloides/sangue , Alcaloides/isolamento & purificação , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Medicina Tradicional Chinesa , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
10.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1633-1640, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489043

RESUMO

According to the major differences of agricultural characters among various Aconitum carmichaelii cultivars, the lateral roots of Ai-leaf and Dahua-leaf A.carmichaelii plants were selected as the research objects. And the Illumina Hiseq high-throughput platform was used for transcriptome sequencing, assembly and annotation. We mostly focused the activity differential transcripts, metabolism pathways and enrichment functions. The results showed that a total of 52.23 Gb nucleotide bases were obtained from 6 A.carmichaelii transcriptome databases, with 52 471 unigenes and 28 765 matched annotation. There were 1 052 transcripts of the two kinds of A.carmichaelii with a difference of more than 2 times, 808 of which were annotated. Through GO and COG analysis, they were found to mainly concentrate in metabolic processes, cell processes, catalytic processes and transport processes, connections and other functions. KEGG analysis showed that 262 DEGs were enriched in 78 metabolic pathways, such as starch and sucrose metabolism, plant hormone signaling, carbon compounded transport etc. It was implied that many genes in Dahua-leaf A.carmichaelii regulated the conversion of starch to small molecules such as sucrose, glucose and maltose, while some other genes regulated the accumulation of amino acids, which may be the important biological principles for the formation of the differences between the quality and disease resistance of two leaf types of A.carmichaelii. This study will provide reference datas for A.carmichaelii breeding research.


Assuntos
Aconitum , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular
11.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1901-1908, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489076

RESUMO

To study the correlation between toxicity and efficacy of different processed Aconiti Kusnezoffii Radix productsin industrial production, in order to define the optimal processing method for "attenuation-preservation effects". The HPLC method was used to determine the content of six aconitine alkaloids in Aconiti Kusnezoffii Radix and its different processed products. The Bliss method was used to determine the half-lethal dose(LD_(50)) or the maximum dose of Aconiti Kusnezoffii Radix and its different processed products in mice. The toluene-induced ear swelling method and the acetic acid twist method were used to investigate the anti-inflammatory and analgesic effects of different processed products. The results showed that: ① the total amount of diester alkaloids incrude Aconiti Kusnezoffii Radix was 0.358 8%; the total amount of diester alkaloids in Aconiti Kusnezoffii Radix prepared by pharmacopoeia-based boiling method was 0.002 2%, and the total amount of monoester alkaloids was 0.036 2%; the total amount of diester alkaloids in Aconiti Kusnezoffii Radix produced by atmospheric steaming method was 0.006 0%, and the total amount of monoester alkaloids was 0.056 7%; ② the LD_(50) of Aconiti Kusnezoffii Radix was 5.4 g·kg~(-1),and the maximum dose of processed products by two methods were 133.34 g·kg~(-1); pathological observation showed that compared with the normal group, the two kinds of processed products of Aconiti Kusnezoffii Radix had certain damage to the heart, liver and kidney; ③products processed by pharmacopoeia-based boiling method and atmospheric steaming method had anti-inflammatory and analgesic effects(P<0.01 or P<0.05). The anti-inflammatory and analgesic effects were as follows: the atmospheric steaming method was superior to the pharmacopoeia-based boiling method. The above results suggest that the crude Aconiti Kusnezoffii Radixis more toxic. The atmospheric steaming method can significantly reduce the toxicity, while retaining its good anti-inflammatory and analgesic effects, which is significantly better than the pharmacopoeia-based boiling method. The atmospheric steaming process is simple and easy to operate, and suitable for industrial production.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Aconitina/análise , Animais , Cromatografia Líquida de Alta Pressão , Camundongos
12.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2073-2081, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495556

RESUMO

The iterative innovation of processing technology is one of the important tasks in studies on processing of traditional Chinese medicine(TCM). It is also the prerequisite for modern, refined, automatic and intelligent manufacturing of TCM pieces. Microwave processing is a new fire processing technique developed in the recent 30 years, with a unique thermodynamic form, and energy transfer and transformation laws. Moreover, it owns the advantages of a high processing efficiency, good product properties and low production energy consumption, with great application prospects. This paper introduced the study overview of microwave expansion technology in the food industry, reviewed the origin of microwave processing technology of TCM, and expounded the basic concept, principle and main purpose of microwave processing technology used in TCM. Then, the impacts of drug factors and microwave factors on the microwave processing effect were summarized, the industrial equipment that could be used for microwave processing was listed, and the impacts of microwave heating on starch, polysaccharide, protein and other components in Chinese herbal medicines were analyzed. Furthermore, the study advance of microwave processing of 14 herbs was investigated, including Aconiti Lateralis Radix Praeparaia, Galli Gigerii Endothelium Corneum and Asini Corii Colla; and the appearance and components of herbs processed by traditional processing method and microwave processing method were compared, so as to reveal the opportunities and challenges of microwave processing technology in the industrial transformation. We hoped that the systematic study of microwave processing technology could provide new ideas and techniques for the high-quality and high-level development of the TCM pieces industry in the new era, and promote its inheritance, innovation and transformation.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Micro-Ondas , Controle de Qualidade
13.
BMC Plant Biol ; 20(1): 137, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245411

RESUMO

BACKGROUND: Flower longevity plays an important role in pollen dispersal and reproductive success in plants. In dichogamous plants, the duration of anthesis as well as the time allocated to male and female functions can vary in response to intrinsic factors (e.g., flowering time and resource allocation) and pollination context along a growth season. However, the fitness consequences of phenological dynamics have rarely been examined. This study aims to unravel the potential causes driving variation in flower longevity, duration of sex phases, and phenotypic sex during a flowering season of strongly protandrous Aconitum gymnandrum, and particularly reproductive consequences of the phenological pattern. RESULTS: Population floral sex ratio shifted from completely male at the beginning to completely female at the end of the season, as is common in other protandrous plants. Phenological dynamics of the floral sex ratio and the duration of sex phases caused a shift from femaleness to maleness in the mean phenotypic sex over the whole season. Floral longevity was negatively correlated with flower size and positively affected by temperature. Early flowers within inflorescences rather than early-flowering individuals emphasized the duration of female over male phase. Owing to the dominance of male-phase flowers, early flowering for individual flowers and plants, or female-biased sex resulted in higher pollen deposition per flower and seed set. At the flower level, flower longevity positively affected female reproductive success, while the effect of flower size was negative. By contrast, plant-level female reproductive success was negatively affected by flower longevity but positively correlated to flower size. CONCLUSIONS: The major result of this study lies in elucidating the relationship between variation in phenological sex expression and floral longevity and their fitness consequences of protandrous A. gymnandrum. The contrasting results on female fitness for individual flowers and plants contribute to our current understanding of the adaptive significance of floral longevity.


Assuntos
Aconitum/fisiologia , Flores , Longevidade , Adaptação Fisiológica , Flores/crescimento & desenvolvimento , Flores/fisiologia , Organismos Hermafroditas/fisiologia , Polinização/fisiologia , Reprodução/fisiologia , Estações do Ano , Razão de Masculinidade , Tundra
14.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1082-1089, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237450

RESUMO

Some Chinese herbal medicine needs to be processed before it can be used as medicine, especially toxic Chinese medicine. Highly toxic Aconti Kusnezoffii Radix(Caowu in Chinese) is widely used in traditional Chinese medicine and Mongolian medicine. In traditional Chinese medicine, Caowu is usually processed by boiling with water(CW) until no white part inside and being tasted without tongue-numbing. In Mongolian medicine, it is usually soaked in Chebulae Fructus(Hezi in Chinese) decoction for several days(CH). Both methods could reduce toxicity according to reports. The biggest difference between CW and CH is that CW needs to be heated for 4-6 h, while CH needs Hezi as processing adjuvants. To explore the toxicity reduction mechanism of CW and CH, we studied the contents of various compounds in Caowu processed by two methods by UPLC-Orbitrap-MS. The results indicated that CW had 14 new ingredients, such as 14-O-anisoylneoline and dehydro-mesaconitine, while N-demethyl-mesaconitine and aconitine disappeared. At the same time, it could significantly decrease the content of diester diterpenoid alkaloids and increase the contents of monoester diterpenoid alkaloids and amine-diterpenoid alkaloids. CH had 9 new ingredients from Hezi, like gallic acid, chebulic acid and shikimic acid. Neither the kinds nor the contents of compositions from Caowu in CH changed little. This suggested that the processing mechanism of CW reduced highly toxic components(diester diterpenoid alkaloids) and increased the content of lowly toxic components(monoester diterpenoid alkaloids and amine-diterpenoid alkaloids). Attenuated principle of CH may be related to the components of Hezi. In this experiment, the conclusion shows that the chemical constituents of CW and CH are essentially different, and the two methods have different toxicity reduction principles.


Assuntos
Aconitum/química , Alcaloides/análise , Medicamentos de Ervas Chinesas/análise , Aconitina , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Medicina Tradicional Chinesa
15.
Fa Yi Xue Za Zhi ; 36(1): 115-119, 2020 Feb.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32250090

RESUMO

Abstract: Aconitum is one of the most widely used Chinese herbal medicines, and aconitine is the major toxic component in it. Aconitine can induce a variety of arrhythmias, resulting in death. Acute ethanol consumption causes arrhythmia as well. Poisoning cases caused by aconitum medicinal liquor are frequently encountered in the practice of forensic medicine. The molecular mechanisms of myocardial toxicity of these two drugs have much in common, and both of them affect the sodium channel, calcium channel and potassium channel of myocardial cell membrane and so on. This paper analyzes and discusses the possible co-effects of ethanol-aconitine on cardiomyocyte channel proteins, by reviewing researches on the mechanism of cardiotoxicity of ethanol and aconitine in recent years, in order to provide ideas and references for the research on the molecular mechanism of arrhythmia caused by combined poisoning.


Assuntos
Arritmias Cardíacas , Aconitina , Aconitum , Medicamentos de Ervas Chinesas , Etanol , Humanos
16.
Sci Rep ; 10(1): 2720, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066766

RESUMO

The study of intracellular gene transfer may allow for the detection of interesting evolutionary processes such as ancient polyploidization. We compared 24 plastid genomes (plastomes) from tribe Delphinieae, one from tribe Nigelleae and one from tribe Ranunculeae, including five newly sequenced genomes. The functional transfers of the plastids rpl32 and rps16 to the nucleus in tribe Delphinieae were identified. Unexpectedly, we discovered multiple divergent copies of the nuclear-encoded plastid rpl32 in the genus Aconitum. Phylogenetic and synonymous substitution rate analyses revealed that the nuclear-encoded plastid rpl32 underwent two major duplication events. These ancient gene duplication events probably occurred via multiple polyploidization events in Aconitum between 11.9 and 24.7 Mya. Furthermore, our sequence rate analysis indicated that the eight plastid-encoded rpl subunits in Aconitum had a significantly accelerated evolutionary rate compared to those in other genera, suggesting that highly divergent paralogs targeted to the plastid may contribute to an elevated rate of evolution in plastid rpl genes. In addition, heteroplasmy of the plastid matK from two Aconitum species suggested the existence of potentially functional plastid maturases in its plastome. Our results provide insight into the evolutionary history of the tribe Delphinieae.


Assuntos
Aconitum/genética , Evolução Biológica , Delphinium/genética , Genomas de Plastídeos , Nigella/genética , Proteínas de Plantas/genética , Plastídeos/genética , Aconitum/classificação , Sequência de Bases , Núcleo Celular/genética , Delphinium/classificação , Endorribonucleases/genética , Duplicação Gênica , Genoma de Planta , Nigella/classificação , Nucleotidiltransferases/genética , Poliploidia , Proteínas Ribossômicas/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
17.
Am J Chin Med ; 48(1): 1-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32054304

RESUMO

Pain is an unpleasant sensory and emotional experience in many diseases and is often caused by intense or damaging stimuli. Pain negatively affects the quality of life and increases high health expenditures. Drugs with analgesic properties are commonly used to relieve pain, but these Western medications could be overwhelmed by side effects including tolerance and addiction. Herbal medicines may provide alternative measures for pain management. In this review paper, after introduction of Chinese medicine theory and treatment modality, emphasis is placed on the application of Chinese herbs and herbal formulations in pain management. Three of the most commonly used herbs, i.e., Corydalis yanhusuo, Ligusticum chuanxiong, and Aconitum carmichaeli, are reviewed. Subsequently, using this ancient medical remedy, Chinese herbal formulation in treating common medical conditions associated with pain, such as headache/migraine, chest pain, abdominal pain, low back pain, neuropathic pain, osteoarthritis, and cancer pain, is presented. Chinese herbal medicines could be considered as a complementary and integrative approach in the modern armamentarium in combating pain.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Manejo da Dor/métodos , Dor/tratamento farmacológico , Aconitum/química , Corydalis/química , Humanos , Ligusticum/química , Medicina Tradicional Chinesa , Estrutura Molecular , Qualidade de Vida
18.
J Ethnopharmacol ; 252: 112581, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31968215

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The herbs of Aconitum are the essential Traditional Chinese medicine and have played an indispensable role in many Asian countries for thousands of years to treat critical illnesses, and chronic, stubborn diseases. However, Aconitum may induce severe neurotoxicity and even death. So far the mechanism of Aconitum penetrating the blood-brain barrier (BBB) is still unclear. AIM OF THE STUDY: To determine whether influx transporters contribute to the brain uptake of the highly toxic alkaloids in Aconitum including aconitine (AC), mesaconitine (MA) and hypaconitine (HA). MATERIALS AND METHODS: The uptake of AC, MA and HA was characterized using in vitro hCMEC/D3 model and in situ mouse brain perfusion. In hCMEC/D3 cells, the effect of incubation temperature, time, initial drug concentration, energy (NaN3), extracellular and intracellular pH (FCCP and NH4Cl), the prototypical substrates/inhibitors of known organic cation transporting carriers and trans-stimulation (pre-incubating with pyrilamine and diphenhydramine) on the cellular uptake were studied. In addition, the effect of silencing OCTN1, OCTN2 and PMAT by specific siRNA was investigated. In mice, the contribution of the proton-coupled antiporter on the brain uptake of Aconitum was investigated by chemical inhibition. RESULTS: In hCMEC/D3 cells, AC, MA and HA were each taken up in a temperature-, time- and concentration-dependent manner, which were reduced by NaN3 and FCCP. Regulation of extracellular and intracellular pH as well as trans-stimulation studies showed that AC, MA and HA were transported by a proton-coupled antiporter expressed at the plasma membrane that could also transport pyrilamine and diphenhydramine. Each uptake was markedly inhibited by various cationic drugs, but insensitive to the prototypical substrates/inhibitors of identified organic cation transporting carriers, such as OCTs, PMAT, MATEs and OCTNs. In addition, silence of OCTN1, OCTN2 and PMAT had no significant inhibitory effect on the uptake of AC, MA and HA. In mice, the brain uptake of each alkaloid measured by in situ brain perfusion was suppressed by diphenhydramine when the transport capacity of P-gp/Bcrp at the BBB was chemically inhibited. CONCLUSIONS: A novel proton-coupled organic cation antiporter plays a predominant role in the blood to brain influx of AC, MA and HA at the BBB, and thus affect the safety of Aconitum species.


Assuntos
Aconitina/análogos & derivados , Aconitum , Antiporters/metabolismo , Barreira Hematoencefálica/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Aconitina/farmacologia , Animais , Linhagem Celular , Humanos , Masculino , Camundongos Endogâmicos ICR , Proteínas de Transporte de Cátions Orgânicos/genética , Prótons , RNA Interferente Pequeno/genética
19.
Carbohydr Polym ; 230: 115586, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887942

RESUMO

α-Glycosidase is an essential target for the management of postprandial serum glucose in diabetic patients. Therefore, the interest has been growing in the screening of α-glycosidase inhibitor from natural resource. In the present study, the structure and α-glycosidase inhibitory activity of a polysaccharide (named as ACPP-1) from Aconitum coreanum were investigated. Based on the results from high performance gel permeation chromatography, GC-MS and 1D/2D nuclear magnetic resonance spectroscopy, ACPP-1 was a highly-linear polysaccharide with a molecular weight of 34.0 kD and containing over 90 % of glucose. It was composed of (1→4)-α-d-Glcp and α-Araf. ACPP-1 exhibited a dose-dependent inhibitory eff ;ect against α-glycosidase activity in vitro and the IC50 value was ∼0.8 mg/mL. In oral starch tolerance test, treatment with ACPP-1 (800 mg/kg) significantly improved the starch tolerance in mice. Taken together, this study provided a potential intervention and management for postprandial hyperglycemia by the polysaccharide fraction from A. coreanum.


Assuntos
Aconitum/química , Inibidores de Glicosídeo Hidrolases/química , Polissacarídeos/química , alfa-Glucosidases/química , Animais , Cromatografia em Gel , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Camundongos , Peso Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/ultraestrutura , alfa-Glucosidases/farmacologia , alfa-Glucosidases/ultraestrutura
20.
Fitoterapia ; 141: 104477, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927015

RESUMO

Extensive phytochemical investigation from the roots of Aconitum kirinense Nakai led to the identification of fifteen new compounds, including four ranaconitine type C18-diterpenoid alkaloids (kirisines A-D, 1-4), one lappaconitine type C18-diterpenoid alkaloid (kirisine E, 5), seven denudatine type C20-diterpenoid alkaloids (kirisines F-L, 6-12), and three napelline type C20-diterpenoid alkaloids (kirisines M-O, 13-15), together with 25 known ones. Their structures were elucidated by extensive spectroscopic analyses. Among them, compounds 1 and 2 are rare diterpenoid alkaloid with 9,14-methylenedioxy group, and the latter also has a rare chloro-substituent. The diterpenoid alkaloids isolated were C18, C19 and C20-category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The isolated compounds were tested for neuroprotective activity and acetylcholinesterase inhibitory activity. Compounds 7, 18, 30 and 40 which exhibited moderate activity at 80 µM against acetylcholinesterase.


Assuntos
Aconitum/química , Alcaloides/química , Diterpenos/química , Linhagem Celular Tumoral , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Humanos , Modelos Moleculares , Estrutura Molecular , Neuroblastoma , Neurônios/efeitos dos fármacos
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