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1.
Ecotoxicol Environ Saf ; 202: 110851, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32673966

RESUMO

Arsenic is a harmful and toxic substance to the growth and development of plants. Salicylic acid (SA) acts as a signaling molecule, plays pivotal roles in the overall growth and development of plants under various environmental stresses. Artemisinin extracted from the leaves of A. annua helps in malarial treatment. The present investigation is aimed to find out the possible ameliorative role of exogenously-applied salicylic acid (SA) on two varieties of Artemisia annua L., namely 'CIM-Arogya' and 'Jeevan Raksha' under arsenic (As) stress conditions. For this, growth, physiological and biochemical characterization, and artemisinin production was assessed. The various treatments applied on the plants were Control, 10-6 M SA, 10-5 M SA, 45 mg kg-1As, 45 mg kg-1 As + 10-6 M SA, and 45 mg kg-1 As + 10-5 M SA. Arsenic at 45 mg kg-1 of soil, reducing the overall performance of both varieties at 90 and 120 DAP. However, the levels of antioxidants were enhanced in As-stressed plants, and the supplementation of SA further increased these antioxidants in SA-treated plants. It has been observed that minimum reduction in growth and yield occurs with enhanced production of artemisinin in the case of 'CIM-Arogya' compared to 'Jeevan Raksha' under As stress (45 mg kg-1 of soil). Leaf-applied SA significantly increased the content (49.0% & 43.4%) and yield (53.3% & 46.3%) of artemisinin in both tolerant and sensitive varieties as compared to their respective controls. Thus, the variety 'CIM-Arogya' showed tolerant behavior over 'Jeevan Raksha' and is much adapted to higher As stress.


Assuntos
Arsênico/toxicidade , Artemisia annua/fisiologia , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Artemisia annua/crescimento & desenvolvimento , Artemisia annua/metabolismo , Artemisininas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Oxidativo , Folhas de Planta/metabolismo , Ácido Salicílico/farmacologia , Solo , Estresse Fisiológico/efeitos dos fármacos
2.
PLoS One ; 15(6): e0234410, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516341

RESUMO

The Eupatorium adenophorum have widespread invaded the karst ecosystem of southwest China and threatened the regional native community stability. Arbuscular mycorrhizae (AM) plays an important role in promoting growth for host plants via root external mycelia. However, whether AM regulates plant root traits underlying competition between invasive and native species via mycorrhizal networks in karst habitats, remains unclear. An experiment was conducted in a microcosm composed of two planting compartments flanking a competition compartment. The invasive E. adenophorum and native Artemisia annua were each placed in one of the two planting compartments with or without Glomus etunicatum fungus. The nutrient access treatments included the competitive utilization (Cu), single utilization (Su) and non-utilization (Nu) by using different nylon meshes allowed or prevented mycelium passing to acquire nutrients from the competition compartment. Root traits and nutrients of the two species were analyzed. The results showed that AM fungi had differential effects on root traits and nutrients of E. adenophorum and A. annua seedlings, which increased dry weight, length, surface area, volume, tips and branching points in roots, specific root length and volume, root nitrogen (N) and phosphorus (P) contents under Cu, Su and Nu treatments. AM fungus was also associated with decreases in the average diameter for both species. Under the Cu treatment, E. adenophorum had significantly greater length, surface area, volume, tips and branching points of roots, specific root traits, and root N and P than A. annua. AM fungi changed root phenotypes and nutrient uptake for both invasive and native plant species via interconnected mycorrhizal networks. Overall, our results suggest that through mycorrhizal networks, the invasive plant experiences greater benefits than the native plant in the nutrient competition, which fosters root morphological developments in karst soil.


Assuntos
Ageratina/metabolismo , Micorrizas/metabolismo , Microbiologia do Solo , Artemisia annua/metabolismo , China , Ecossistema , Micélio , Micorrizas/fisiologia , Nitrogênio , Nutrientes , Fósforo , Raízes de Plantas/crescimento & desenvolvimento , Plantas Daninhas/metabolismo , Solo , Árvores/crescimento & desenvolvimento
3.
Planta Med ; 86(12): 867-875, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32557519

RESUMO

Artemisia annua tea is a popular dosage form used to treat and prevent malaria in some developing countries. However, repeated drinking leads to an obviously decreased efficacy, which may be related to the induction of metabolizing enzymes by artemisinin. In the present study, the ability of different components in A. annua to activate the pregnane X receptor and constitutive androstane receptor was evaluated by the dual luciferase reporter gene system. The changes in mRNA and protein expression of CYP3A4 and CYP2B6 were determined by quantitative real-time PCR and Western blotting. Results showed that in the pregnane X receptor-mediated CYP3A4 reporter gene system, chrysosplenetin and arteannuin B exhibited a weak induction effect on pregnane X receptor wt, while arteannuin A had a strong induction effect on pregnane X receptor wt and pregnane X receptor 370 and a weak induction effect on pregnane X receptor 163. In the pregnane X receptor-mediated CYP2B6 reporter gene system, arteannuin A had a moderate induction effect on pregnane X receptor wt and pregnane X receptor 379, and a weak induction effect on pregnane X receptor 403, while arteannuin B had a weak induction effect on pregnane X receptor wt and pregnane X receptor 379. Arteannuin A had a strong induction effect on constitutive androstane receptor 3 in constitutive androstane receptor-mediated CYP3A4/2B6 reporter gene systems, while arteannuin B showed a weak induction effect on constitutive androstane receptor 3 in the constitutive androstane receptor-mediated CYP2B6 reporter gene system. The mRNA and protein expressions of CYP3A4 and CYP2B6 were increased when the pregnane X receptor or constitutive androstane receptor was activated. Various components present in A. annua differentially affect the activities of pregnane X receptor isoforms and the constitutive androstane receptor, which indicates the possibility of a drug-drug interaction. This partly explains the decline in efficacy after repeated drinking of A. annua tea.


Assuntos
Artemisia annua , Receptores de Esteroides/genética , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A , Indução Enzimática , Hepatócitos , Extratos Vegetais , Receptores Citoplasmáticos e Nucleares
4.
Bull Environ Contam Toxicol ; 104(5): 609-618, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32128603

RESUMO

The effects of copper (Cu) exposure on growth and physiological characteristics of three genotypes (CN-12, Cim-Sanjeevani and Cim-Arogya) of Artemisia annua L. were elucidated. The plants were grown under naturally illuminated greenhouse conditions and were harvested after physiological maturity (120 days after sowing). Results suggest that 10 mg kg- 1 Cu significantly enhanced the growth and physiological parameters like enzyme activities, photosynthesis. At higher concentrations, Cu inhibited the growth, biomass, photosynthetic parameters; while increased lipid peroxidation in all the genotypes. The activities of antioxidant enzymes viz. catalase, peroxidase and superoxide dismutase were upregulated by the Cu stress. The highest applied concentration of Cu (60 mg kg- 1) proved most toxic for plants. Moreover, artemisinin content was increased upto 10 mg kg- 1 of Cu treatment, compared with control, however, the artemisinin accumulation decreased at higher doses of Cu in all the genotypes. On the basis of studied parameters, Cim-Arogya was found to be most tolerant among all for Cu toxicity.


Assuntos
Antioxidantes/metabolismo , Artemisia annua/efeitos dos fármacos , Artemisininas/metabolismo , Cobre/toxicidade , Fotossíntese/efeitos dos fármacos , Artemisia annua/genética , Artemisia annua/crescimento & desenvolvimento , Catalase/metabolismo , Relação Dose-Resposta a Droga , Genótipo , Peroxidação de Lipídeos , Peroxidase/metabolismo , Solo/química , Poluentes do Solo/análise , Superóxido Dismutase/metabolismo
5.
Food Chem ; 312: 126070, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31911352

RESUMO

To evaluate the quality of Artemisia annua L., an accurate HPLC-DAD method has been developed, validated and applied to the simultaneous quantification of five flavonoids, two coumarins and four sesquiterpenes. An LC-ESI-QTOF-MS/MS confirmation method has been utilized to avoid false-positive results. Principal component analysis and hierarchical cluster analysis results indicated that their contents had obvious regional characteristics. Samples with high contents of artemisinin (8.24 ± 2.92 mg/g) and isorhamnetin (0.28 ± 0.25 mg/g) are mainly distributed south of the Yangtze River, and samples with high contents of scopolin (0.46 ± 0.22 mg/g), scopoletin (1.05 ± 0.17 mg/g), chrysosplenol D (0.64 ± 0.14 mg/g), casticin (1.07 ± 0.23 mg/g), arteannuin B (0.69 ± 0.18 mg/g) and artemisinic acid (3.02 ± 1.00 mg/g) are mainly distributed in eastern and northern China. Geographic content differences of the components in A. annua indicate the potential differences in the health-promoting effects of its clinical application.


Assuntos
Artemisia annua/química , Cumarínicos/análise , Flavonoides/análise , Compostos Fitoquímicos/análise , Sesquiterpenos/análise , China , Cromatografia Líquida de Alta Pressão/métodos , Análise de Componente Principal , Espectrometria de Massas em Tandem
6.
J Photochem Photobiol B ; 202: 111652, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760374

RESUMO

The Biocompatibility and stability of nanoparticles using plants have been widely investigated due to its applications in the biomedical industry. Currently, there is a growing interest in nanoparticles in bone remodelling. Artemisia annua is an herbal plant commonly used in the treatment of various ailments. This study investigated the zinc oxide nanoparticles (ZnO NPs) using the green synthesis technique from A. annua and the effects of A. annua ZnO-NPs on osteoblast differentiation and inhibition of osteoclast formation. The formulated ZnO-NPs from A. annua were characterized by using various spectroscopic and microscopic methods Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), and UV-Visible spectroscopy. The disc diffusion method was adopted to test the antimicrobial efficacy of ZnO-NPs. The viability of MG-63 cells were assayed by MTT test and Osteogenic-related assays like Real-time PCR and Mineralization assay were adopted to determine the effects of A. annua ZnO-NPs on the multiplication and differentiation of human osteoblast-like MG-63 cells. The characterization of A. annua ZnO-NPs revealed the crystalline nature with high zinc content and the presence of bioactive compounds from A. annua extract. The synthesized A. annua ZnO-NPs indicate significant antimicrobial potential. Besides, A. annua ZnO-NPs enhanced the proliferation, differentiation, and mineralization without causing significant cytotoxic impact on MG-63 cells. These effects indicate that A. annua ZnO-NPs can both stimulate bone formation via the differentiation of MG-63 cells. Hence, it was concluded that A. annua ZnO-NPs can be a promising agent for the treatment of bone deformities and bone-related diseases, however further research also required to explore the clear mechanism of A. annua ZnO-NPs in the formation and differentiation of MG-63 cells.


Assuntos
Artemisia annua/química , Diferenciação Celular , Proliferação de Células , Nanopartículas Metálicas/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Artemisia annua/metabolismo , Cálcio/metabolismo , Candida/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Humanos , Nanopartículas Metálicas/toxicidade , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química , Óxido de Zinco/química
7.
Ecotoxicol Environ Saf ; 189: 109988, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31767459

RESUMO

Tribolium casteneum is a major stored grains pest causing huge loss by secreting toxic quinones' which make the grains unfit for human consumption. Increasing concern about the fast-growing resistance in T. casteneum against fumigants has evoked more intense research worldwide. Therefore, finding an eco-friendly alternative for the management of the pest is of great importance. In this study, the insecticidal activity of the essential oils (EOs) of Artemisia annua is evaluated. Chemical composition of the EOs eluted with methanol and petroleum ether was analysed through Gas chromatography-mass spectrometry (GC-MS). The result has reported a total of 13 & 16 compounds in the methanol and petroleum ether EOs respectively. In contact toxicity studies, adults were found more susceptible to the petroleum ether EOs (LD50 = 0.43 mg adult-1) than the methanolic EOs (LD50 = 1.87 mg adult-1). Petroleum ether EOs was also superior in fumigant assays against both the adults (0.81 mg L air-1) and larvae (0.65 mg L air-1). Moreover, the same was also recorded as a strong repellent. The bio-molecular studies conducted to gain an insight into the extent of metabolic disturbances inflicted in the treatment sets has shown a significant increase in Lipid peroxidase and decrease (p˂0.01) in protein, Acetylcholinesterase, Glutathione S Transferees, Reduced Glutathione level. This indicates the major signs of oxidative stress in the treatment sets. The Results ascertain the knowledge to develop natural insecticides from Artemisia annua using a potential solvent to be used in the future as an efficient management tool against T. casteneum.


Assuntos
Artemisia annua/química , Controle de Insetos/métodos , Inseticidas/farmacologia , Óleos Voláteis/farmacologia , Tribolium/fisiologia , Animais , Repelentes de Insetos/química , Repelentes de Insetos/isolamento & purificação , Repelentes de Insetos/farmacologia , Inseticidas/química , Inseticidas/isolamento & purificação , Larva/metabolismo , Larva/fisiologia , Dose Letal Mediana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Tribolium/metabolismo
8.
Magn Reson Chem ; 58(3): 232-244, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31733071

RESUMO

Artemisia annua is a promising and potent antimalarial herbal drug. This activity has been ascribed to its component artemisinin, a sesquiterpene lactone. The ability to determine artemisinin and its known analogs in plant extracts is an especially difficult task because the compounds are present in low concentrations, are thermolabile, and lack ultraviolet or fluorescent chromophores. We report herein a facile and rapid 1-D 1 H, 1-D total correlation spectroscopy, 2-D 1 H-13 C heteronuclear single quantum coherence, and 1 H-13 C heteronuclear multiple bond correlation nuclear magnetic resonance techniques for the simultaneous identification and quantification of artemisinin and five of its analogs along with five flavonoids, an aromatic ketone, and camphor (in total, 13 compounds) in crude diethyl ether A. annua extract without the need of laborious isolation of the individual analytes. The above method was validated in terms of precision, linearity, and limit of detection. The analytical results were found to be in excellent agreement with those obtained with the use of the time consuming high-performance liquid chromatography with diode-array detection and liquid chromatography with tandem mass spectrometry for the compounds that standards were available.


Assuntos
Antimaláricos/química , Artemisia annua/química , Artemisininas/análise , Flavonoides/análise , Extratos Vegetais/química , Cânfora/química , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos/métodos , Cetonas/química , Limite de Detecção , Espectroscopia de Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
9.
Phytochem Anal ; 31(1): 5-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31370102

RESUMO

INTRODUCTION: Artemisinin (1), a well-known natural antimalarial drug, is a sesquiterpene lactone that contains a unique peroxide bridge. Since its discovery, the amount of research into the analysis of artemisinin has increased considerably, and it has been further intensified since the Noble Prize win by Tu Youyou in the year 2015 for the discovery of artemisinin. OBJECTIVE: To review literature on the extraction and analysis of artemisinin, published during 2017-present, and to present an appraisal of those methods. METHODOLOGY: Extensive literature search was carried out which involved, but not limited to, the use of, various databases, like Web of Knowledge, PubMed and Google Scholar, and relevant published materials including published books. The keywords used, in various combinations, with artemisinin being present in all combinations, in the search were artemisinin, Artemisia annua, analysis, extraction, quantitative, qualitative and quality control. RESULTS: During the period covered in this review, several methods of analysis of artemisinin have been reported, the most of which were liquid chromatography (LC)-based methods. However, the use of new methods like near-infrared analysis, fluorometirc analysis and molecular imprinting, and a significant increase in the use of computational tools have been observed. Mainly several methods involving supercritical fluid extraction and ultrasound-assisted extraction of artemisinin have dominated the extraction area. CONCLUSIONS: Newer analytical tools, as well as improved protocols for the known analytical tools, for qualitative and quantitative determination of artemisinin (1), have been made available by various researchers during the period covered by this review. Supercritical fluid extraction and ultrasound-assisted extraction are still the methods of choice for extraction of artemisinin.


Assuntos
Antimaláricos , Artemisia annua , Artemisininas , Cromatografia Líquida , Extratos Vegetais
10.
J Ethnopharmacol ; 247: 112281, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31600559

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. is a heat-clearing Chinese medicine and well-known for its antimalarial constituent, artemisinin. It has gained increasing attention for its anti-inflammatory and immunoregulatory activities. Interestingly, the crude polysaccahrides of A. annua exhibited potent anticomplement activity. This study was to isolate and characterize its anticomplement homogeneous polysaccharides from A. annua, and reveal the relationship between structures and anticomplement activities of the isolated polysaccharides. MATERIALS AND METHODS: Water-soluble crude polysaccharides from the aerial parts of A. annua were extracted and fractionated by DEAE-cellulose and Sephacryl S-300 gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, methylation and NMR analysis were performed to characterize the structures of homogeneous polysaccharides. Their anticomplement activities and targeting components in the complement activation cascade were evaluated by hemolytic assays. RESULTS: Three homogeneous polysaccharides (AAP01-1, AAP01-2 and AAP01-3) were obtained from A. annua. AAP01-1 was composed of seven monosaccharides, including mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose. AAP01-2 and AAP01-3 had similar monosaccharides with AAP01-1, except the absence of glucuronic acid. They were all branched acidic heteropolysaccharides with different contents of galacturonic acid (8%, 28% and 15% for AAP01-1, AAP01-2 and AAP01-3, respectively). AAP01-2 showed potent anticomplement activity with CH50 value of 0.360 ±â€¯0.020 mg/mL through the classical pathway and AP50 value of 0.547 ±â€¯0.033 mg/mL through the alternative pathway. AAP01-3 exhibited slightly weaker activity (CH50: 1.120 ±â€¯0.052 mg/mL, AP50: 1.283 ±â€¯0.061 mg/mL), while AAP01-1 was inactive. Moreover, AAP01-2 acted on C1q, C3, C4, C5 and C9 components and AAP01-3 interacted with C3, C4 and C5 components in the activation cascade of complement system. CONCLUSION: These results indicated that the relatively high contents of galacturonic acid were important for anticomplement activities of the polysaccharides from A. annua. The anticomplement polysaccharides are another kind of bioactive constituents conferring heat-clearing effects of A. annua.


Assuntos
Artemisia annua/química , Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Polissacarídeos/farmacologia , Animais , Bioensaio , Inativadores do Complemento/química , Inativadores do Complemento/isolamento & purificação , Proteínas do Sistema Complemento , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Cobaias , Hemólise/efeitos dos fármacos , Ácidos Hexurônicos/química , Ácidos Hexurônicos/isolamento & purificação , Ácidos Hexurônicos/farmacologia , Modelos Animais , Estrutura Molecular , Componentes Aéreos da Planta/química , Coelhos , Relação Estrutura-Atividade
11.
J Chromatogr A ; 1615: 460785, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-31864725

RESUMO

Artemisia annua L. is an annual weedy herb belonging to the Asteraceae family. As a traditional Chinese herb, Artemisia annua is a major source of artemisinin, an antimalarial drug. In addition to artemisinin, this plant contains several other molecular families presenting a wide range of biological properties. To facilitate the screening and the identification of active compounds, the present study describes their targeting by combining the dereplication information obtained by means of Molecular Networks and a crude extract fractionation by Centrifugal Partition Chromatography to obtain and test simplified fractions. This simple and fast approach was developed focused on the antioxidant activity of Artemisia annua with the aim of screening and identifying the antioxidant molecules for further cosmetic uses. Firstly, the aerial parts of Artemisia annua were extracted and their antioxidant activity was evaluated by DPPH, ABTS, CUPRAC, FRAP and iron (II) chelating assays. Extract with a positive response was subjected to UHPLC-HRMS with autoMS/MS experiments in order to build a Molecular Network using the GNPS (Global Natural Products Social Molecular Networking) platform. Secondly, the crude extract was fractionated using CPC with an adapted Arizona solvent system. The fractions obtained were evaluated for antioxidant activity to focus on active compounds, which were located on the Molecular Network and identified thanks to their MS/MS spectra. Using this approach, the major phenolic compound contributing to the antioxidant activity of Artemisia annua extract was identified.


Assuntos
Antioxidantes/análise , Artemisia annua/química , Técnicas de Química Analítica/métodos , Cromatografia Líquida , Extratos Vegetais/química , Antioxidantes/isolamento & purificação , Fracionamento Químico , Espectrometria de Massas em Tandem
12.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4992-4999, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872610

RESUMO

Artemisinin was isolated from traditional Chinese herb Artemisia annua for treating malaria. A series of derivatives,like dihydroartemisinin,artesunate,artemether,artether,had the same core chemical structure,and sesquiterpene lactone containing peroxide bridge constitute the basic chemical structure. Besides anti-malaria,artemisinin family drugs were found to ameliorate many different diseases,which have attracted wide attention in recent years. Among different diseases,artemisinin family drugs were found to have T lymphocytes immunomodulation effects,including activation,proliferation,differentiation,apoptosis and subsets function. Because T cell immunologic response is the key point of many diseases,and impact the pathogenic process,therapeutic effect and prognosis,the drug studies with it as the target have become hotspots in recent years. Studies of artemisinin family drug on T cell immunomodulation were still at the initial stage and involved in different disease; furthermore,T cell immune process involves complicated molecular mechanism,it is imperative to summarize the advance of current studies for further systematic explanation and exploration of their characteristics and mechanisms. This article will summarize the research progress of artemisinin family drugs for malaria,autoimmune disease,hypersensitivity reaction,tumor,schistosomiasis and AIDS relating to T cell immune modulation,so as to provide basic and professional reference for related research and application.


Assuntos
Antimaláricos , Artemisia annua , Artemisininas/farmacologia , Imunomodulação , Linfócitos T
13.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4285-4292, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872711

RESUMO

Artemisinin is a kind of sesquiterpene lactone containing endoperoxide bridge,which is the most effective anti-malarial drug at present. However,low content of artemisinin in Artemisia annua,ranging from 0. 1%-1. 0% of dry weight,as well as the complicated extraction process have resulted in low yield and high cost of artemisinin,making it difficult to meet market demand.Based on the development of high-throughput sequencing and molecular biology,the related enzyme genes and transcription factors involved in the artemisinin metabolic pathway were cloned and identified. Metabolic engineering and synthetic biology methods to modify the original metabolic pathway of A. annua and genetic engineering in heterologous host cells have become one of the hotspots in this field. Therefore,the molecular mechanism of artemisin biosynthesis,different strategies of genetic modifications of A. annua,and the research status and application prospect of artemisinin synthesis in heterologous host cells( Nicotiana benthamiana,Physcomitrella patens) were summarized in our review,hoping to provide molecular basis and theoretical basis for breeding new varieties of A. annua with high artemisinin output.


Assuntos
Antimaláricos , Artemisia annua , Artemisininas , Engenharia Metabólica , Fatores de Transcrição
14.
Molecules ; 24(21)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31652784

RESUMO

: Metabolic engineering is an integrated bioengineering approach, which has made considerable progress in producing terpenoids in plants and fermentable hosts. Here, the full biosynthetic pathway of artemisinin, originating from Artemisia annua, was integrated into the moss Physcomitrella patens. Different combinations of the five artemisinin biosynthesis genes were ectopically expressed in P. patens to study biosynthesis pathway activity, but also to ensure survival of successful transformants. Transformation of the first pathway gene, ADS, into P. patens resulted in the accumulation of the expected metabolite, amorpha-4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates the presence of endogenous promiscuous enzyme activity, possibly cytochrome P450s, in P. patens. Introduction of three pathway genes, ADS-CYP71AV1-ADH1 or ADS-DBR2-ALDH1 both led to the accumulation of artemisinin, hinting at the presence of one or more endogenous enzymes in P. patens that can complement the partial pathways to full pathway activity. Transgenic P. patens lines containing the different gene combinations produce artemisinin in varying amounts. The pathway gene expression in the transgenic moss lines correlates well with the chemical profile of pathway products. Moreover, expression of the pathway genes resulted in lipid body formation in all transgenic moss lines, suggesting that these may have a function in sequestration of heterologous metabolites. This work thus provides novel insights into the metabolic response of P. patens and its complementation potential for A. annua artemisinin pathway genes. Identification of the related endogenous P. patens genes could contribute to a further successful metabolic engineering of artemisinin biosynthesis, as well as bioengineering of other high-value terpenoids in P. patens.


Assuntos
Artemisininas/metabolismo , Bryopsida , Proteínas de Plantas , Plantas Geneticamente Modificadas , Artemisia annua/genética , Bryopsida/genética , Bryopsida/metabolismo , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo
15.
J Sep Sci ; 42(21): 3330-3339, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31483950

RESUMO

The traditional antimalarial herb Artemisia annua L., from which artemisinin is isolated, is widely used in endemic regions. It has been suggested that artemisinin activity can be enhanced by flavonoids in A. annua; however, how fast and how long the flavonoids are present in the body remains unknown. In the present study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of three major flavonoids components, i.e. chrysosplenol D, chrysoplenetin, and artemetin and their glucuronidated metabolites in rats after oral administrations of A. annua extracts at a therapeutic ultra-low dose. The concentration of the intact form was determined directly, and the concentration of the glucuronidated form was assayed in the form of flavonoids aglycones, after treatment with ß-glucuronidase/sulfatase. The method was linear in the range of 0.5-300.0 ng/mL for chrysoplenetin and artemetin, and 2-600 ng/mL for chrysosplenol D. All the validation data conformed to the acceptance requirements. The study revealed a significantly higher exposure of the flavonoid constituents in conjugated forms in rats, with only trace intact from. Multiple oral doses of A. annua extracts led to a decreased plasma concentration levels for three flavonoids.


Assuntos
Antimaláricos/sangue , Artemisia annua/química , Flavonoides/sangue , Glucuronídeos/sangue , Extratos Vegetais/sangue , Administração Oral , Animais , Antimaláricos/administração & dosagem , Antimaláricos/farmacocinética , Cromatografia Líquida de Alta Pressão , Flavonoides/administração & dosagem , Flavonoides/farmacocinética , Glucuronídeos/administração & dosagem , Glucuronídeos/farmacocinética , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem
16.
Plant Cell Physiol ; 60(12): 2826-2836, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504880

RESUMO

In Artemisia annua plants, glandular trichomes (GTs) are responsible for the biosynthesis and secretion of sesquiterpene lactones including artemisinin/arteannuin B. Nonspecific lipid transfer proteins (LTPs) in plants bind and carry lipid molecules across the cell membrane and are also known as secretary proteins. Interestingly, the transcripts of LTP genes are exceptionally abundant in the GTs of A. annua. In the present study, we isolated two trichome-specific LTP genes (AaLTP3 and AaLTP4) from a Korean ecotype of A. annua. AaLTP3 was expressed abundantly in shoots, whereas AaLTP4 was expressed in flowers. The GUS signal driven by the AaLTP3 or AaLTP4 promoter in transgenic A. annua plants revealed that the AaLTP3 promoter was active on hair-like non-GTs and that the AaLTP4 promoter was active on GTs. Analysis of enhanced cyan fluorescent protein (ECFP) fluorescence fused with the AaLTP3 or AaLTP4 protein in transgenic tobacco revealed that ECFP florescence was very bright on secreted lipids of long GTs. Moreover, the florescence was also bright on the head cells of short trichomes and their secreted granules. Immunoblotting analysis of GT exudates in petioles of A. annua revealed a strong positive signal against the AaLTP4 antibody. Overexpression of AaLTP3 or AaLTP4 in transgenic A. annua plants resulted in enhanced production of sesquiterpene lactones (arteannuin B, artemisinin, dihydroartemisinic acid and artemisinic acid) compared with those of wild type. The present study shows that LTP genes (AaLTP3 or AaLTP4) play important roles in the sequestration and secretion of lipids in GTs of A. annua, which is useful for the enhanced production of sesquiterpene lactones by genetic engineering.


Assuntos
Artemisia annua/metabolismo , Lactonas/metabolismo , Sesquiterpenos/metabolismo , Tricomas/genética , Artemisia annua/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética
17.
J Mycol Med ; 29(3): 201-209, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31378442

RESUMO

Candida albicans is a polymorphic opportunistic commensal that causes both superficial and systemic fungal infections especially in immunocompromised patients. Biologically synthesized silver nanoparticles (AgNPs) have emerged as potential antifungal agents. The present work evaluates the antifungal activity of Artemisia annua synthesized AgNPs against three Candida species (C. albicans ATCC 90028, C. tropicalis ATCC 750 and C. glabrata ATCC 90030). The in vitro effect of AgNPs was investigated for fungal growth, sterol content, secretion of hydrolytic enzymes and yeast-to-hyphal transition. The green synthesized AgNPs were effective against all the three species with minimum inhibitory concentration (MIC) in the range 80-120µgml-1. Candida glabrata showed greater sensitivity for AgNPs followed by Candida tropicalis and C. albicans. AgNPs at 4MIC were as effective as fluconazole (FLC) and caused only 5% haemolysis while FLC caused 50% haemolysis at the same concentration. The secretion of hydrolytic enzymes was the lowest in case of AgNP exposed C. glabrata. Yeast-to-hyphal transition was significantly reduced in treated C. albicans cells and showed disfigured morphology in SEM images. The decrease in ergosterol content was slightly higher (94%) in both C. glabrata and C. tropicalis in comparison to C. albicans (69%). Green synthesized AgNPs thus have immense potential as an antifungal and can play a crucial role in the management of Candida infections especially those caused by C. glabrata.


Assuntos
Antifúngicos/farmacologia , Artemisia annua/química , Candida/efeitos dos fármacos , Nanopartículas Metálicas/química , Prata/farmacologia , Candida/enzimologia , Candida/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Peptídeo Hidrolases/metabolismo , Fosfolipases/metabolismo
18.
Oxid Med Cell Longev ; 2019: 1615758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354901

RESUMO

Artemisia annua has been used for centuries in Traditional Chinese Medicine. Although used as an antimalarial drug, its active compound artemisinin and the semisynthetic derivatives have also been investigated for their anticancer properties, with interesting and promising results. The aims of this research were to evaluate (i) the cytotoxicity and the antiproliferative effect of pure artemisinin and a hydroalcoholic extract obtained from A. annua on the D-17 canine osteosarcoma cell line and (ii) the intracellular iron concentration and its correlation with the cytotoxic effects. Both artemisinin and hydroalcoholic extract induced a cytotoxic effect in a dose-dependent manner. Pure artemisinin caused an increase of cells in the S phase, whereas the hydroalcoholic extract induced an evident increase in the G2/M phase. A significant decrease of iron concentration was measured in D-17 cells treated with pure artemisinin and hydroalcoholic extract compared to untreated cells. In conclusion, although preliminary, the data obtained in this study are indicative of a more potent cytotoxic activity of the hydroalcoholic extract than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis. Considering the similarities between human and canine osteosarcomas, progress in deepening knowledge and improving therapeutic protocols will probably be relevant for both species, in a model of reciprocal translational medicine.


Assuntos
Artemisia annua/química , Artemisininas/química , Osteossarcoma/tratamento farmacológico , Extratos Vegetais/química , Animais , Linhagem Celular , Cães , Humanos , Medicina Tradicional Chinesa
19.
Parasitol Res ; 118(9): 2705-2713, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359134

RESUMO

Artemisinin, extracted from a medicinal herb Artemisia annua, is widely used to treat malaria and has shown potent anticancer activity. Artemisinin has been found to be effective against experimental visceral and cutaneous leishmaniasis. Despite extensive research to understand the complex mechanism of resistance to artemisinin, several questions remain unanswered. The artesunate (ART)-resistant line of Leishmania donovani was selected and cellular mechanisms associated with resistance to artemisinin were investigated. ART-resistant (AS-R) parasites showed reduced susceptibility towards ART both at promastigote and amastigote stage compared with ART sensitive (WT) parasites. WT and AS-R parasites were both more susceptible to ART at the early log phase of growth compared with late log phase. AS-R parasites were more infective to the host macrophages (p < 0.05). Evaluation of parasites' tolerance towards host microbicidal mechanisms revealed that AS-R parasites were more tolerant to complement-mediated lysis and nitrosative stress. ROS levels were modulated in presence of ART in AS-R parasites infected macrophages. Interestingly, infection of macrophages by AS-R parasites led to modulated levels of host interleukins, IL-2 and IL-10, in addition to nitric oxide. Additionally, AS-R parasites showed upregulated expression of genes of unfolded protein response pathway including methyltransferase domain-containing protein (HSP40) and flagellar attachment zone protein (prefoldin), that are reported to be associated with ART resistance in Plasmodium falciparum malaria. This study presents in vitro model of artemisinin-resistant Leishmania parasite and cellular mechanisms associated with ART resistance in Leishmania.


Assuntos
Antiprotozoários/administração & dosagem , Artemisininas/administração & dosagem , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/genética , Leishmaniose Visceral/imunologia , Extratos Vegetais/administração & dosagem , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Artemisia annua/química , Artesunato/administração & dosagem , Feminino , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/imunologia , Interações Hospedeiro-Parasita , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Leishmania donovani/crescimento & desenvolvimento , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/fisiopatologia , Macrófagos/imunologia , Camundongos Endogâmicos BALB C
20.
Carbohydr Res ; 483: 107753, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31362136

RESUMO

Artemisia annua is cultivated mainly for isolation of artemisinin, a potent antimalarial compound. Moderate salt stress has been proved to increase the artemisinin synthesis by the plant. The aim of this study was to evaluate the influence of salt stress on physiological parameters and cell wall polysaccharides of A. annua. Plants subjected to salt stress displayed reduction in the biomass and length and showed high damage of cellular membranes. Cell wall polysaccharides extracted from aerial parts with hot water, EDTA and NaOH also exhibited modifications in the yield and monosaccharide composition. The main changes were found in the pectic polysaccharides: increase of homogalacturonan domain, increase of neutral side chains and increase in the methyl esterification. 1H NMR analyses of pectins indicated that for A. annua, arabinans have an important role in coping with salt stress. Hemicellulose domain was also modified under salt stress, with increased xylose contents. The results indicated adaptations in the cell wall of A. annua under salt stress.


Assuntos
Artemisia annua/crescimento & desenvolvimento , Polissacarídeos/química , Estresse Salino , Artemisia annua/química , Biomassa , Parede Celular/química , Componentes Aéreos da Planta/química , Extratos Vegetais/química
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