A severe case of Plasmodium falciparum malaria imported by a French traveler from Cameroon to French Guiana despite regular intake of Artemisia annua herbal tea

ABSTRACT The use of herbal tea with Artemisia annua by travelers and traditional communities in Africa has increased in recent years as a supposed form of malaria prophylaxis, although its use is not recommended due to lack of efficacy. The risk of severe malaria complications that can lead to death is real regarding said behavior, and awareness needs to be raised. We report a case of severe Plasmodium falciparum malaria imported in the Amazon rainforest by a traveler returning from Cameroon who treated himself with Artemisia annua herbal tea.

Flavonoid glycosides from the water extract of Artemisia annua L / 药学学报

Twenty one flavonoid glycosides were isolated and purified from n-butanol portion of the water extract of A. annua by various chromatographic techniques such as HP-20 macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as axillarin-7-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside (1), orientin (2), apigenin-6-C-β-D-glucopyranosyl-8-C-β-L-arabinopyranoside (3), apigenin-6-C-β-D-galactopyranosyl-8-C-β-L-arabinopyranoside (4), apigenin-6-C-β-L-arabinopyranosyl-8-C-β-D-glucopyranoside (5), apigenin-6-C-α-L-arabinofuranosyl-8-C-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (7), apigenin-6-C-α-L-arabinopyranosyl-8-C-β-D-glucopyranoside (8), vicenin-2 (9), patuletin-7-O-β-D-glucopyranoside (10), luteolin-6-C-glucopyranoside (11), vitexin (12), kaempferol-3-O-β-galactopyranosyl-(1→2)-β-glucopyranoside (13), quercetin-7-O-β-D-glucopyranoside (14), patuletin-3-O-β-D-glucopyranoside (15), 7-O-methyl-quercetagetin-6-O-β-D-glucopyranoside (16), quercetin-3-O-β-D-glucopyranoside (17), nepitrin (18), rutin (19), kaempferol-3-O-β-sophoroside (20), and patuletin-3-O-rutinoside (21). Compound 1 is a new compound, compounds 2, 4, 6, 7, 10, 11, 13, 15, 16, 18, 20 and 21 are isolated from A. annua for the first time. In the anti-inflammatory assay, compound 1 inhibited the release of IL-6 from LPS-induced RAW264.7 cells to significantly degrees with the high (100 μmol·L-1), medium (50 μmol·L-1), low (25 μmol·L-1) concentration.

Mechanism of Artemisia annua L. in GIOP with kidney-yin deficiency based on network pharmacology / 药学实践杂志

Objective To predict and preliminarily verify the potential targets and related signaling pathways of Artemisia annua L. in treating glucocorticoid-induced osteoporosis (GIOP) with kidney-yin deficiency by network pharmacology and in vitro experiments. Methods The pharmacological targets of Artemisia annua L. were obtained from TCMSP database and were converted to gene names through Uniprot database. The target genes of GIOP with kidney-yin deficiency were obtained from GeneCards database, OMIM database and Drugbank database, and the common target genes were obtained by cross analysis with drug target gene. Protein-protein interaction (PPI) network was constructed by String database, and visualization analysis and core targets screening were performed by Cytoscape 3.9.0. All common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis through Metascape database. Finally, the prediction results were verified by in vitro experiments. Results Ninety-eight targets of Artemisia annua L. to GIOP with kidney-yin deficiency were screened, including 17 core genes. The results of GO and KEGG functional enrichment analysis indicated that Artemisia annua L. treating GIOP with kidney-yin deficiency was related to biological processes such as hormonal response, positive regulation of cell death and extracellular stimulation response, et al, as well as signaling pathways such as PI3K/AKT, AGE/RAGE, MAPK and IL-17 et al. The number of genes enriched in PI3K/AKT signaling pathway was the largest. In vitro experiment results showed that Artemisia annua L. promoted the proliferation of osteoblasts damaged by dexamethasone (DEX), increased alkaline phosphatase activity, activated PI3K/AKT pathway, and promoted the phosphorylation of AKT. Conclusion Artemisia annua L. treating GIOP with kidney-yin deficiency has the characteristics of multi-targets and multi-pathway, which could promote the proliferation and differentiation of osteoblasts through multiple pathways. The PI3K/AKT signaling pathway is an important pathway. Artemisia annua L. treating GIOP with kidney-yin deficiency might be related to its ability to promote the PI3K/AKT signaling pathway and promote the phosphorylation of AKT.

Study on pharmacodynamics and pharmacokinetics of Qinglian ningxin capsule in ischemic arrhythmia model rats / 中国药房

OBJECTIVE To study th e pharmacodynamics and pha rmacokinetics of Qinglian ningxin capsule in rats with ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group ，model control group ， Qinglian ningxin capsule group （4.00 g/kg），Artemisia annua group（1.43 g/kg），Coptis chinensis group（0.42 g/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；model control group and blank control group were given normal saline intragastrically ，once a day ，for consecutive 7 days. After last medication ，except for blank control group，other groups were given Posterior pituitary injection via tail vein （1 u/kg） to induce ischemic arrhythmia model. electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin capsule model group and Qinglian ningxin capsule control group （4.00 g/kg），A. annua model group and A. annua control group （1.43 g/kg），C. chinensis model group and C. chinensis control group （0.42 g/kg）. After the rats in each model group were injected with Posterior pituitary injection （1 u/kg）via tail vein ，administration groups were given relevant drugs intragastrically ， and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time points（0，0.25，0.75，1，2，4，6，8，12 and 24 h）. The concentrations of berberine hydrochloride and artemisinin in plasma were determined by HPLC ，and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with the model control groups ，Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and redu ced the prolongation of PR interval and QT interval significantly ，and the effects were generally better than those of A. annua group and C. chinensis group（P＜0.05）. Compared with A. annua control group and C. chinensis control group ，cmax，AUC0－t and AUC 0－∞ of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule control group，while CL was decreased significantly ；t1/2z of artemisinin was prolonged significantly （P＜0.05）. Compared with Qinglian ningxin capsule control group ，cmax（except artemisinin ），AUC0－t，AUC0－∞，MRT0－t and MRT 0－∞（except artemisinin ）of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule model group ，while CL was decreased significantly（P＜0.05）. CONCLUSIONS Qinglian ningxin capsule could significantly improve ischemic arrhythmia better than A. annua and C. chinensis ，and can improve the absorption of berberine hydrochloride and artemisinin in model rats and slow down their elimination.

Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua

Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

Induction of secondary metabolites on nanoparticles stress in callus culture of Artemisia annua L / Indução de metabólitos secundários no estresse de nanopartículas em cultura de calos de Artemisia annua L

Nanoparticles are known bio elicitors in plant biotechnology. Different concentrations of ZnO, CuO and CoO nanoparticles were used for the enhanced accumulation of secondary metabolites and antioxidant activities in the callus derived from root, shoot and leaf of Artemisia annua L. Biomass of callus was somehow affected on high concentrations of Nps. Phenolic content was observed maximum (60µg) in shoot callus at 0.1mg/l of CuONps. Total antioxidant activity was observed maximum (33µg) in root callus at 0.1mg/l of ZnOnps. Total reducing power maximum (33µg) was observed in root callus at concentration of 0.05 mg/l of CoONps. Maximum radical scavenging activity was observed in shoot callus at 0.05mg/l of ZnONps. Rutin gallic acid and caffic acid were also determined in most of the samples by HPLC. The study concludes that different Nps have positive effect on the induction of secondary metabolites in A.annua plant.

Nanopartículas são bio-elicitores conhecidos em biotecnologia de plantas. Diferentes concentrações de nanopartículas de ZnO, CuO e CoO foram usadas para o acúmulo aumentado de metabólitos secundários e atividades antioxidantes no calo derivado da raiz, parte aérea e folha de Artemisiaannua L. A biomassa do calo foi de alguma forma afetada em altas concentrações de Nps. O conteúdo fenólico foi observado no máximo (60 µg) no calo da parte aérea a 0,1 mg / l de CuONps. A atividade antioxidante total foi observada no máximo (33µg) no calo radicular a 0,1mg / l de ZnOnps. O poder de redução total máximo (33µg) foi observado no calo radicular na concentração de 0,05 mg / l de CoONps. Atividade máxima de eliminação de radicais foi observada no calo da parte aérea a 0,05mg / l de ZnONps. O ácido rutina-gálico e o ácido caffic também foram determinados na maioria das amostras por HPLC. O estudo conclui que diferentes Nps têm efeito positivo na indução de metabólitos secundários na planta de A.annua.

Establishment of allergic rhinitis mouse model sensitized by Artemisia annua and its immunological study / 中华微生物学和免疫学杂志

Objective:To optimize the BALB/c mouse rhinitis model sensitized by Artemisia annua pollen allergen, and explore the humoral and cellular immune indicators that can be used for the evaluation of allergic reactions. Methods:Using BALB/c mice as experimental animals, using Artemisia annua pollen allergen extract as sensitizing protein, through different content of the main allergen Art a1 and different sensitization times, different immunization programs were set to immunize mice subcutaneously, One week and five weeks after the last immunization, Artemisia annua pollen allergen extract containing 50 μg/ml and 500 μg/ml Art a1 was used for nasal stimulation, once a day, for 1 week each time.Observe the allergic reaction of mice, detect the pathological changes of nasal tissues, determine the levels and dynamic changes of antigen-specific IgE, IgG1, IgG2a and other antibodies in the serum of each group of mice. and detect the changes in the number of antigen-specific IL-4, IL-5, IL-2, IFN-γ and other lymphocytes in the spleen of mice. Results:Sensitized mice showed obvious scratching and sneezing reactions after being stimulated by antigen; obvious allergic inflammation appeared in nasal tissue; The increase in serum level of Artemisia annua pollen-specific IgE antibody was significantly correlated with the challenge antigen; The antigen-specific IL-4 lymphocytes in the spleen of the sensitized mice were significantly increased, but the IFN-γ-specific lymphocytes did not change significantly. Conclusions:The successful establishment of a mouse model of Artemisia annua pollen allergen allergy is the first domestic use of ELISPOT technology to detect an increase in the number of antigen-specific IL-4 lymphocytes in Artemisia annua allergy mice, laying a foundation for the subsequent evaluation of the efficacy of preparations for desensitization treatment basis.

An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment / 中西医结合学报

Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised: would A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties? PubMed/MEDLINE, Scopus, and Google Scholar were searched for peer-reviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that evidenced the herb's role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins including 3CL

Research on chemical constituents from Artemisia annua Ⅰ / 中国中药杂志

Chemical constituents were isolated and purified from the water extract of Artemisia annua by column chromatography of HP-20 macroporous resin, silica gel, ODS, Sephadex LH-20, HW-40, and semi-preparative RP-HPLC. Their structures were elucidated by physicochemical properties and spectral analyses. As a result, Fifteen compounds were isolated and identified as vitexnegheteroin M(1), sibricose A5(2), securoside A(3), citrusin D(4), annphenone(5), E-melilotoside(6), esculetin(7), scopoletin-7-O-β-D-glucoside(8), eleutheroside B_1(9), chrysosplenol D(10), patuletin-3-O-β-D-glucopyranoside(11), quercetin-7-O-β-D-glucoside(12), rutin(13), apigenin 6,8-di-C-β-D-glucopyranoside(14), isoschaftoside(15), among them, compounds 1-4 were identified from Artemisia for the first time. Additionally, the isolates were evaluated for their inhibitory effects on the production of PGE_2 in LPS-simulated RAW264.7 macrophages. The results showed that compounds 1, 2, 8, and 10-15 could reduce PGE_2 levels, to a certain extent.

Research advances of biosynthesis, in vivo analysis and pharmacokinetics of chemical constituents in Artemisiae Annuae Herba / 中国中药杂志

Artemisiae Annuae Herba is a traditional Chinese medicine for clearing deficiency and heat. It is the only natural source of artemisinin, which is a specific antimalarial drug, and has been widely concerned all over the world. In addition to artemisinin, Artemisiae Annuae Herba also contains many sesquiterpenes, coumarins, flavonoids, volatile oils, polysaccharides and other chemical components, which show antipyretic, anti-inflammatory, antiviral microorganisms, anti-asthma, anti-oxidation, anti-tumor and other pharmacological activities. In addition to their own pharmacological activities, some components could enhance the antimalarial activity of artemisinin through different mechanisms at absorption and metabolism in vivo. In order to understand the pharmacokinetic characte-ristics of the chemical constituents contained in Artemisiae Annuae Herba and provide reference for the full development and clinical utilization of Artemisiae Annuae Herba resources in China, this present paper systematically collated the modern research literatures, and summarized the biosynthesis, in vivo analysis and pharmacokinetics of the chemical constituents in Artemisiae Annuae Herba.

Analysis on Content Differences of Artemisinin and Arteannuin B in Different Provenances of Artemisia annua Under Indoor Hydroponic Conditions / 中国实验方剂学杂志

Objective:To establish a method for the determination of artemisinin and arteannuin B in different <italic>Artemisia annua</italic> germplasms， compare the differences of the two compounds among different <italic>A. annua</italic> germplasm under the condition of hydroponic homogenization and explore the key factors affecting contents of principal compounds in different<italic> A. annua</italic> germplasms. Method:Seedlings from different <italic>A. annua</italic> germplasms were arranged randomly and fed in a hydroponic cultivation system. Contents of artemisinin and arteannuin B were detected by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS） with multi-reaction monitoring mode and ACQUITY UPLC^® BEH C₁₈ column （2.1 mm×100 mm， 1.7 μm）， mobile phase was water-acetonitrile （95∶5， containing 0.1% formic acid， A） and acetonitrile-water （95∶5， containing 0.1% formic acid， B） for gradient elution （0-3.5 min， 25%-1%A； 3.5-3.6 min， 1%-25%A； 3.6-5.0 min， 25%A）， the flow rate was set at 0.4 mL·min^-1. The content differences of artemisinin and arteannuin B in different provenances of <italic>A. annua</italic> were detected and analyzed statistically. Result:The established method had high sensitivity and good separation. A significant difference of artemisinin and arteannuin B contents was observed in different germplasms under the same culture conditions， that is， under the constant temperature of 25 ℃ in hydroponics. The provenance with higher artemisinin content was Yunnan， and the content was 3 810.597 μg·g^-1. The highest strain of arteannuin B was Shanxi provenance germplasm with the content of 1 691.747 μg·g^-1. According to the content of artemisinin， the provenances were arranged as follows：Yunnan， Hainan， Hubei， Guangxi， Zhejiang， Shanxi， Beijing， Shandong， Heilongjiang， and Gansu province germplasms. Correlation analysis showed that there was a significant negative correlation between artemisinin content and latitude of <italic>A. annua</italic>， but there was no significant correlation between contents of artemisinin and arteannuin B and longitude. Conclusion:The contents of artemisinin and arteannuin B among different <italic>A. annua</italic> germplasms were significantly different under the same culture environment， and the dominant factors affecting biosynthesis and accumulation of artemisinin and arteannuin B in <italic>A. annua</italic> may be the genetic background， suggesting that germplasm improvement is the key factor to improve the medicinal quality of <italic>A. annua</italic> in subsequent cultivation.

A new lignan from Artemisiae Annuae Herba / 中草药

Objective: To study the constituents from the dried aboveground part of Artemisia annua. Methods: The chemical constituents were isolated by various chromatographic techniques and their structures were elucidated by spectroscopic analyses and comparison of NMR data with those reported in literatures. Results: Six compounds were obtained and characterized as artelignan (1), scopoletin (2), scoparone (3), chrysosplenol B (4), jaceidin (5) and mikanin (6). Conclusion: Compound 1 is identified as a new compound named artelignan.

Role of Prostaglandins in the Vasodilator Effect of the Aqueous Extract from Artemisia annua Plant in Streptozotocin-induced Diabetic Rats

Aims: One of the most important causes of mortality is vascular complications resulting from diabetes mellitus. Herbal medicines are commonly used for the treatment of cardiovascular conditions in diabetes. Artemisia annua (A. annua) as a medicinal plant has vasculature protective effects in diabetic rats. In the present study, the role of prostaglandins in the vasodilator effect of A. annua aqueous extract in diabetic rats has been studied. Study Design: This animal study was conducted on diabetic rats. Aqueous extract of Artemisia annua was used for diabetic rats. Then, isolated thoracic aortic rings were exposed to indomethacin and after exposure, the contractile responses were measured. Methodology: The studied animals were male Wistar rats (n=36) which were randomly divided into intact, untreated-diabetic, and A. annua aqueous extract treated-diabetic groups. For the induction of diabetes, streptozotocin was intraperitoneally (i.p.) administered (60 mg/kg). A. annua extract-treated group received i.p. 100 mg/kg of extract for one month. After one month, the dose contractile response of isolated aortic rings to phenylephrine (doses of 10-9-10-4 mol/L) in the absence and presence of indomethacin as a prostaglandins inhibitor was determined using isolated tissue setup. Results: Comparison of contractile responses before and after adding indomethacin in treated extract diabetic rats, showed that contractile responses of aorta ring with and without endothelium after adding indomethacin significantly increased at all concentrations of phenylephrine (P<0.05–P<0.0001) while indomethacin in diabetic rats did not effect on contractile response. Conclusions: Since the vasodilator effect of the aqueous extract of A. annua with a concentration of 100 mg/kg of body weight was pronounced even after endothelium removal, it can be claimed that the vasodilator effects of the extract are related to inhibition of prostaglandin generation both indirectly and directly.

Research progress on chemical constituents of Artemisia annua and its pharmacological activities / 中草药

As a commonly used Chinese materia medica, Artemisia annua mainly contains sesquiterpenoids, diterpenes, phenylpropionic acids, coumarins, flavonoids, volatile oil, and other chemical compositions. Its pharmacological activities are anti-malaria, anti-tumor, anti-microbial, anti-parasitic, antipyretic, anti-inflammatory, immunoregulation and so on. The significantly anti-malarial activity has led to its earlier use in the treatment of malaria. In this paper, the chemical constituents and pharmacological activities of A. annua in recent years are reviewed in order to provide a reference for the further development and rational utilization of this plant resource.

Rol genes enhance content of artemisinin and other secondary metabolites in Shennong hybrid of Artemisia annua / 中草药·英文版

Objective: Artemisia annua is the chief source of artemisinin, a potent antimalarial agent, in which other bioactive phytochemicals are also present. Due to low levels of bioactive compounds including artemisinin and flavonoids, it is necessary to increase the level of the secondary metabolites by regulating the expression of rol genes in the plant. Methods: A hybrid variety of A. annua (Hyb1209r, Shennong)developed by the Centre for Novel Agricultural Products, University of York, UK, was selected to produce transgenics of rolB and rolC genes. Genetic transformation was carried out via Agrobacterium tumefaciens GV3101 harboring rolB and rolC genes of Agrobacterium rhizogenes cloned separately. HPLC was used for the qualitative and quantitative analysis of flavonoids and artemisinin. Furthermore, thin layer chromatography (TLC)was also used to analyze artemisinin content. Results: Comparative analysis via HPLC revealed considerable enhancement in the phytochemical content of transgenic A. annua plants as compared to the wild type plant. Transgenics of rolB gene showed an average increase of 321% in rutin, 97.2% in caffeic acid, and 218.4% in myricetin, respectively. In the case of rolC gene transgenics, an average increase of 197.5% in rutin, 76.3% in caffeic acid, and 209.3% in myricetin was observed. Transgenics of rolB and rolC genes showed a 14.3%–28.6% and 2.8%–12.7% increase in artemisinin content respectively by HPLC analysis. TLC analysis showed that an average 142.2% and 110.2% enhancement in artemisinin for rolB and rolC transgenics respectively, compared with the wild type. An enhanced production of total flavonoids (average 30.2% and 25.5% increase in rolB and rolC transgenics, respectively)and total phenolics (average 34.3% and 25.8% increase in rolB and rolC transgenics, respectively)was observed as a result of transformation. Transformed A. annua plants showed improved free radical scavenging activity (average 46.5% and 29.1% increase in rolB and rolC transgenics, respectively)and total reducing power (average 32.7% and 26.4% increase in rolB and rolC transgenics, respectively)compared with untransformed plant. Conclusion: rolB and rolC genes were effective for developing A. annua plants with an enhanced level of phytochemicals.

A new coumarin glycoside isolated from Artemisia annua / 中草药

Objective: To study the chemical constituents with high polarity from the whole herb of Artemisia annua. Methods: The constituents were isolated and purified by column chromatography on Sephadex LH-20, silica gel, ODS, and preparative TLC. The structures were elucidated by the analysis of the spectroscopic data. Results: Fourteen compounds were obtained from the methanol soluble fraction of the 70% ethanol extract of A. annua by maceration at room temperature and identified as artemisiannuside A (1), scopolin (2), 2,4-dihydroxy-6-methoxyacetophenone-4-O-β-D-glucopyranoside (3), methyl caffeate (4), salicylic acid (5), ferulic acid (6), vanillic acid (7), 2,4-dihydroxy-6-methoxyacetophenone (8), homoeriodictyol (9), jaceidin (10), penduletin (11), axillarin (12), eriodictyol (13), and ®-15,16-didehydrocoriolic acid (14), respectively. Conclusion: Compound 1 is a new acylated coumarin glycoside. Compound 14 is isolated from the Artemisia genus for the first time and compound 9 is firstly isolated from A. annua.

Mechanism of high temperature promoting artemisinin biosynthesis in Artemisia annua / 中国中药杂志

Artemisia annua also known as Qinghao, is a kind of traditional Chinese medicine. Its active ingredient is artemisinin, a sesquiterpene lactone compound with a peroxy bridging group structure. A. annua is an effective antimalarial drug. Artemisinin, a secondary metabolite in A. annua, can be induced by many physical and chemical factors, such as salinity, moisture, light, and plant hormones. Temperature, as an important growth factor, also has a great influence on the synthesis of artemisinin. This article aims to study the effect of high temperature on inducing artemisinin biosynthesis in A. annua. The A. annua seedlings were placed at 25, 40 °C, and the samples were taken after 0, 3, 12 and 36 h. The content of artemisinin in each sample was determined by liquid chromatography-mass spectrometry. Total RNA was extracted from the samples, and then transcriptome sequencing and real-time fluorescence quantitative PCR were used to quantitatively analyze the expression of the key enzyme genes in artemisinin synthesis pathway and competition pathway. The results showed that artemisinin content was increased by 20%, 42% and 68% after 3, 12, 36 h of treatment at 40 °C. The expression levels of FDS, ALDH1, CYP71AV1 and ADS were up-regulated by 4.3, 3.3, 2.5, 1.9 times, and the expression levels of SQS and BPS were down-regulated by 37% and 90% respectively. In summary, high temperature can promote the biosynthesis of artemisinin by promoting the expression of synthetase genes in artemisinin synthesis pathway and inhibiting the expression of synthetase genes in artemisinin-competition pathway.

Molecular cloning and characterization of CMK from Artemisia annua / 中国中药杂志

Artemisinin is a preferred medicine in the treatment of malaria. In this study, AaCMK, a key gene involved in the upstream pathway of artemisinin biosynthesis, was cloned and characterized from Artemisia annua for the first time. The full-length cDNA of AaCMK was 1 462 bp and contained an ORF of 1 197 bp that encoded a 399-anomo-acid polypeptide. Tissue expression pattern analysis showed that AaCMK was expressed in leaves, flowers, roots and stems, but with higher expression level in glandular secretory trichomes. In addition, the expression of AaCMK was markedly increased after MeJA treatment. Subcellular localization showed that the protein encoded by AaCMK was localized in chloroplast. Overexpression of AaCMK in Arabidopsis increased the contents of chlorophyll a, chlorophyll b and carotenoids. These results suggest that AaCMK plays an important role in the biosynthesis of terpenoids in A. annua and this research provids a candidate gene that could be used for engineering the artemisinin biosynthesis.

Statues and research strategy of molecular breeding in Artemisia annua / 中国中药杂志

Malaria is one of the three most deadly diseases in the world. Artemisinin is the first line and effective drug for treating malaria, and only can be extracted from Artemisia annua. Therefore, it is of great significance to cultivate new varieties of A. annua with high artemisinin content. Based on the germplasm bank and the whole genome, transcriptome and genetic map, the authors can explore high-quality genes, stress-resistant genes and genetic markers which have been used for rapid breeding of superior varieties of A. annua. So these methods of molecular breeding will become the main breeding direction of A. annua in the future. The breeding times of new varieties of A. annua can be shortened with molecular breeding technology. Based on the genetic background and the current situation of molecular breeding of A. annua, the strategy and technical route of molecular breeding were discussed and worked out in this paper, which provided a guidance and scientific reference for molecular breeding of A. annua in the future.

In vitro and in vivo antileishmanial activity of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans

ABSTRACT INTRODUCTION: Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL. METHODS: The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL. RESULTS: Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion. CONCLUSION: Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.