Project description:KEY MESSAGE : Rooting of Artemisia annua increases trichome size on leaves and helps drive the final steps of the biosynthesis of the sesquiterpene antimalarial drug, artemisinin. Artemisia annua produces the antimalarial drug, artemisinin (AN), which is synthesized and stored in glandular trichomes (GLTs). In vitro-grown A. annua shoots produce more AN when they form roots. This may be a function not of the roots, but rather media components such as the phytohormones, ?-naphthaleneacetic acid (NAA) and 6-benzylaminopurine (BAP), or salts and sucrose used to maintain either rooted or unrooted shoot cultures. We investigated how three main media components altered artemisinic metabolite production, pathway gene transcripts, and GLT formation in both mature and developing leaves in rooted and unrooted cultures. Although transcript levels of AN biosynthetic genes were not altered, AN levels were significantly different, and there were major differences in both artemisinic metabolite levels and trichomes in mature versus developing leaves. For example, NAA induced higher AN production in rooted shoots, but only in mature leaves. In developing leaves, BAP increased GLT density on the leaf surface. When both phytohormones were present, GLTs were larger on young developing leaves, but smaller on mature leaves. Furthermore, although other media components increased GLT density, their size decreased on young leaves, but there was no effect on mature leaves. Roots also appeared to drive conversion of artemisinic precursors towards end products. These results suggest that, while the presence of roots affects AN and trichome production, phytohormones and other media constituents used for in vitro culture of A. annua also exert an influence.
Project description:Background:Artemisia annua is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for Artemisia annua-induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for Artemisia annua-related AR. Methods:This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 Artemisia annua-sensitized eligible patients were randomized in a ratio of 2:1 to receive Artemisia annua-SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced. Results:Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 ± 0.47 vs 1.88 ± 0.42, P < 0.0001 in full analysis set [FAS]; 1.49 ± 0.52 vs 1.95 ± 0.46, P < 0.0001 in per protocol set [PPS]); representing a 22.3% and 23.6% reduction, respectively, relative to placebo. In specifically Artemisia annua monosensitized patients, mean daily CSMRS reductions were demonstrated as 24.1% and 27.0% in the FAS and PPS populations, respectively, when comparing the active treatment to placebo treatment. Similarly, SLIT decreased dTNSS in peak pollen period by 19.0% in FAS and 22.3% in PPS, respectively, relative to placebo. In coincidence, dRMS in peak pollen period was reduced by 22.0% in FAS and 26.0% in PPS. 65.8% patients in SLIT group experienced treatment-related AEs, none of which was serious. Conclusion:This study indicates that SLIT with Artemisia annua drops is an effective and safe treatment option in Chinese patients with Artemisia Annua-induced AR.
Project description:Background: Central Asia is the center of origin and diversification of the Artemisia genus. The genus Artemisia is known to possess a rich phytochemical diversity. Artemisinin is the shining example of a phytochemical isolated from Artemisia annua, which is widely used in the treatment of malaria. There is great interest in the discovery of alternative sources of artemisinin in other Artemisia species. Methods: The hexane extracts of Artemisia plants were prepared with ultrasound-assisted extraction procedures. Silica gel was used as an adsorbent for the purification of Artemisia annua extract. High-performance liquid chromatography with ultraviolet detection was performed for the quantification of underivatized artemisinin from hexane extracts of plants. Results: Artemisinin was found in seven Artemisia species collected from Tajikistan. Content of artemisinin ranged between 0.07% and 0.45% based on dry mass of Artemisia species samples. Conclusions: The artemisinin contents were observed in seven Artemisia species. A. vachanica was found to be a novel plant source of artemisinin. Purification of A. annua hexane extract using silica gel as adsorbent resulted in enrichment of artemisinin.
Project description:BACKGROUND Artemisia annua exerts powerful effects in non-small cell lung carcinoma (NSCLC). Some studies have shown that Artemisia annua possesses the characteristics of new therapeutic drugs for NSCLC patients. However, the underlying molecular mechanism of Artemisia annua anti-NSCLC is not yet fully elucidated because Artemisia annua contains hundreds of ingredients. This study aimed to conduct network pharmacological analysis on the mechanism of action of Artemisia annua against NSCLC. MATERIAL AND METHODS The active ingredients and corresponding potential targets of Artemisia annua were searched and screened in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then through The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) databases to establish NSCLC related targets. Based on the matching results of Artemisia annua potential targets and NSCLC targets, a protein-protein interaction (PPI) network was constructed to analyze the interactions between these targets and topologically screen the central targets. Furthermore, Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment were carried out. RESULTS There were 19 main active ingredients of Artemisia annua screened for target prediction; 40 NSCLC-related common targets were identified via multiple NSCLC databases. The node area and corresponding degree value of AKT1, MYC, CCND1, VEGFA, JUN, MAPK1, EGFR, and ESR1 were large and could be easily found in the PPI network. The aforementioned results were further verified by the analysis of GO biological function and KEGG enrichment analysis. CONCLUSIONS The network pharmacology analysis reveals the molecular biological mechanism of Artemisia annua anti-NSCLC via multiple active components, multi-channels, and multi-targets. This suggests that Artemisia annua might be developed as a promising anti-NSCLC drug.
Project description:Artemisia annua, an annual herb used in traditional Chinese medicine, produces a wealth of monoterpenes and sesquiterpenes, including the well-known sesquiterpene lactone artemisinin, an active ingredient in the treatment for malaria. Here we report three new monoterpene synthases of A. annua. From a glandular trichome cDNA library, monoterpene synthases of AaTPS2, AaTPS5, and AaTPS6, were isolated and characterized. The recombinant proteins of AaTPS5 and AaTPS6 produced multiple products with camphene and 1,8-cineole as major products, respectively, and AaTPS2 produced a single product, ?-myrcene. Although both Mg(2+) and Mn(2+) were able to support their catalytic activities, altered product spectrum was observed in the presence of Mn(2+) for AaTPS2 and AaTPS5. Analysis of extracts of aerial tissues and root of A. annua with gas chromatography-mass spectrometry detected more than 20 monoterpenes, of which the three enzymes constituted more than 1/3 of the total. Mechanical wounding induced the expression of all three monoterpene synthase genes, and transcript levels of AaTPS5 and AaTPS6 were also elevated after treatments with phytohormones of methyl jasmonate, salicylic acid, and gibberellin, suggesting a role of these monoterpene synthases in plant-environment interactions. The three new monoterpene synthases reported here further our understanding of molecular basis of monoterpene biosynthesis and regulation in plant.
Project description:BACKGROUND AND OBJECTIVE:Prior small-scale clinical trials showed that Artemisia annua and Artemisia afra infusions, decoctions, capsules, or tablets were low cost, easy to use, and efficient in curing malaria infections. In a larger-scale trial in Kalima district, Democratic Republic of Congo, we aimed to show A. annua and/or A. afra infusions were superior or at least equivalent to artesunate-amodiaquine (ASAQ) against malaria. METHODS:A double blind, randomized clinical trial with 957 malaria-infected patients had two treatment arms: 472 patients for ASAQ and 471 for Artemisia (248 A. annua, 223 A. afra) remained at end of the trial. ASAQ-treated patients were treated per manufacturer posology, and Artemisia-treated patients received 1?l/d of dry leaf/twig infusions for 7 d; both arms had 28 d follow-up. Parasitemia and gametocytes were measured microscopically with results statistically compared among arms for age and gender. RESULTS:Artemisinin content of A. afra was negligible, but therapeutic responses of patients were similar to A. annua-treated patients; trophozoites cleared after 24? h, but took up to 14 d to clear in ASAQ-treated patients. D28 cure rates defined as absence of parasitemia were for pediatrics 82, 91, and 50% for A. afra, A. annua and ASAQ; while for adults cure rates were 91, 100, and 30%, respectively. Fever clearance took 48 ?h for ASAQ, but 24 ?h for Artemisia. From D14-28 no Artemisia-treated patients had microscopically detectable gametocytes, while 10 ASAQ-treated patients remained gametocyte carriers at D28. More females than males were gametocyte carriers in the ASAQ arm but were unaffected in the Artemisia arms. Hemoglobin remained constant at 11?g/dl for A. afra after D1, while for A. annua and ASAQ it decreased to 9-9.5? g/dl. Only 5.0% of Artemisia-treated patients reported adverse effects, vs. 42.8% for ASAQ. CONCLUSION:A. annua and A. afra infusions are polytherapies with better outcomes than ASAQ against malaria. In contrast to ASAQ, both Artemisias appeared to break the cycle of malaria by eliminating gametocytes. This study merits further investigation for possible inclusion of Artemisia tea infusions as an alternative for fighting and eradicating malaria.
Project description:Traditional remedies have been used for thousand years for the prevention and treatment of infectious diseases, particularly in developing countries. Of growing interest, the plant Artemisia annua, known for its malarial properties, has been studied for its numerous biological activities including metabolic, anti-tumor, anti-microbial and immunomodulatory properties. Artemisia annua is very rich in secondary metabolites such as monoterpenes, sesquiterpenes and phenolic compounds, of which the biological properties have been extensively studied. The purpose of this review is to gather and describe the data concerning the main chemical components produced by Artemisia annua and to describe the state of the art about the biological activities reported for this plant and its compounds beyond malaria.
Project description:Artemisia annua is an important medicinal plant producing the majority of the antimalarial compound artemisinin. Jasmonates are potent inducers of artemisinin accumulation in Artemisisa annua plants. As the receptor of jasmonates, the F-box protein COI1 is critical to the JA signaling required for plant development, defense, and metabolic homeostasis. AaCOI1 from Artemisia annua, homologous to Arabidopsis AtCOI1, encodes a F-box protein located in the nuclei. Expressional profiles of the AaCOI1 in the root, stem, leaves, and inflorescence was investigated. The mRNA abundance of AaCOI1 was the highest in inflorescence, followed by in the leaves. Upon mechanical wounding or MeJA treatment, expression of AaCOI1 was upregulated after 6 h. When ectopically expressed, driven by the native promoter from Arabidopsis thaliana, AaCOI1 could partially complement the JA sensitivity and defense responses, but fully complemented the fertility, and the JA-induced anthocyanin accumulation in a coi1-16 loss-of-function mutant. Our study identifies the paralog of AtCOI1 in Artemisia annua, and revealed its implications in development, hormone signaling, defense, and metabolism. The results provide insight into JA perception in Artemisia annua, and pave the way for novel molecular breeding strategies in the canonical herbs to manipulate the anabolism of pharmaceutic compounds on the phytohormonal level.