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Stephanie H Kung, Sean Lund, Abhishek Murarka, Derek McPhee, Chris J Paddon
The antimalarial drug artemisinin is a natural product produced by the plant Artemisia annua . Extracts of A. annua have been used in Chinese herbal medicine for over two millennia. Following the re-discovery of A. annua extract as an effective antimalarial, and the isolation and structural elucidation of artemisinin as the active agent, it was recommended as the first-line treatment for uncomplicated malaria in combination with another effective antimalarial drug (Artemisinin Combination Therapy) by the World Health Organization (WHO) in 2002...
2018: Frontiers in Plant Science
Jiaqin Wang, Yanying Zhou, Man Wang, Wentao Bi, Hongli Li, David Da Yong Chen
A fast, simple, efficient, and high-throughput analytical protocol using deep eutectic solvents (DES) for mechanochemical extraction (MCE) combined with direct analysis in real time mass spectrometry (DART-MS) was developed to quantify heat-labile bioactive compounds artemisinin (AN), arteannuin B, and artemisinic acid from Aretemisia annua. MCE is performed at room temperature, and target analytes are released into DESs within seconds; this method demonstrated multiple advantages over traditional extraction methods and organic solvents...
March 6, 2018: Analytical Chemistry
Ting-Ting Shi, Xiao-Bo Zhang, Lan-Ping Guo, Hui Wang, Zhi-Xian Jing, Lu-Qi Huang
Dao-di herbs are preferred by long-term clinical application of Chinese medicine, they are produced in a specific area and affected by the specific production and processing methods. Dao-di herbs have a high reputation, compared with other regions produced by the same kind of herbs with good quality, good efficacy and stable quality characteristics. Geo-herbal is a unique concept that has been formed by the history of Chinese civilization for thousands of years and the history of Chinese medicine. According to the definition of geo-herbal, it can be seen that there are some differences in the quality and efficacy of the same kind of medicinal herbs in different regions, and there is some similarity in the specific area...
November 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Sun Kyoung Lee, Hyungkeun Kim, Junhee Park, Hyun-Jeong Kim, Ki Rim Kim, Seung Hwa Son, Kwang-Kyun Park, Won-Yoon Chung
The activities of osteoclasts and osteoblasts are balanced to maintain normal bone density. Many pathological conditions cause osteoclastic bone resorption in excess of osteoblastic bone formation, resulting in osteoporosis. We found that oral administration of Artemisia annua ethanol extract (AaE) or major components, artemisinin and arteannuin B, to ovariectomized (OVX) mice prevented bone loss, as verified by examining three-dimensional images and bone morphometric parameters derived from microcomputed tomography analysis, as well as serum levels of bone turnover markers and proinflammatory cytokines...
December 11, 2017: Scientific Reports
Xiaobo Zhang, Yuping Zhao, Lanping Guo, Zhidong Qiu, Luqi Huang, Xiaobo Qu
BACKGROUND: Daodi-herb is a part of Chinese culture, which has been naturally selected by traditional Chinese medicine clinical practice for many years. Sweet wormwood herb is a kind of Daodi-herb, and comes from Artemisia annua L. Artemisinin is a kind of effective antimalarial drug being extracted from A. annua. Because of artemisinin, Sweet wormwood herb earns a reputation. Based on the Pharmacopoeia of the People's Republic of China (PPRC), Sweet wormwood herb can be used to resolve summerheat-heat, and prevent malaria...
2017: PloS One
Xixian Chen, Congqiang Zhang, Heng-Phon Too
One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in Saccharomyces cerevisiae, and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated. The first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step, and a series of N-terminal truncation and transcriptional tuning improved the enzymatic activity...
August 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Paulina Fuentes, Tegan Armarego-Marriott, Ralph Bock
Metabolic pathway engineering by transgene expression from the plastid (chloroplast) genome offers significant attractions, including straightforward multigene engineering by pathway expression from operons, high transgene expression levels, and increased transgene containment due to maternal inheritance of plastids in most crops. In addition, it provides direct access to the large and diverse metabolite pools in chloroplasts and non-green plastid types. Here, we review recent progress with extending the toolbox for plastid engineering and highlight selected applications in the area of metabolic engineering, including the combined engineering of nuclear and plastid genomes for the production of artemisinic acid, the direct harness of chloroplast reducing power for the synthesis of dhurrin and the use of an edible host for the production of astaxanthin...
February 2018: Current Opinion in Biotechnology
Kinjalka Ghosh, M G Muddeshwar, Manoj Lokhande, Kanjaksha Ghosh
BACKGROUND: We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albumin (IMA) assay as a prognostic marker for severe malaria in a medical college setting. METHODS: Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy. RESULTS: 100 consecutive patients (50 with vivax and 50 with falciparum malaria) were evaluated...
2017: Mediterranean Journal of Hematology and Infectious Diseases
James Reed, Michael J Stephenson, Karel Miettinen, Bastiaan Brouwer, Aymeric Leveau, Paul Brett, Rebecca J M Goss, Alain Goossens, Maria A O'Connell, Anne Osbourn
Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products...
July 2017: Metabolic Engineering
Dongming Ma, Gui Li, Fatima Alejos-Gonzalez, Yue Zhu, Zhen Xue, Aimin Wang, Hui Zhang, Xing Li, Hechun Ye, Hong Wang, Benye Liu, De-Yu Xie
We recently characterized a gene-terpene network that is associated with artemisinin biosynthesis in self-pollinated (SP) Artemisia annua, an effective antimalarial plant. We hypothesize that an alteration of gene expression in the network may improve the production of artemisinin and its precursors. In this study, we cloned an isopentenyl pyrophosphate isomerase (IPPI) cDNA, AaIPPI1, from Artemisia annua (Aa). The full-length cDNA encodes a type-I IPPI containing a plastid transit peptide (PTP) at its amino terminus...
August 2017: Plant Journal: for Cell and Molecular Biology
Philipp Arendt, Karel Miettinen, Jacob Pollier, Riet De Rycke, Nico Callewaert, Alain Goossens
Saponins are a structurally diverse family of triterpenes that are widely found as main constituents in many traditional plant-based medicines and often have bioactivities of industrial interest. The heterologous production of triterpene saponins in microbes remains challenging and only limited successful pathway engineering endeavors have been reported. To improve the production capacities of a Saccharomyces cerevisiae saponin production platform, we assessed the effects of several hitherto unexplored gene knockout targets on the heterologous production of triterpenoids...
March 2017: Metabolic Engineering
Liangyun Zhou, Guang Yang, Haifeng Sun, Jinfu Tang, Jian Yang, Yizhan Wang, Thomas Avery Garran, Lanping Guo
This study aims to elucidate the underlying molecular mechanisms of artemisinin accumulation induced by Cd. The effects of different Cd concentrations (0, 20, 60, and 120 μmol/L) on the biosynthesis of Artemisia annua L. were examined. Intermediate and end products were quantified by HPLC-ESI-MS/MS analysis. The expression of key biosynthesis enzymes was also determined by qRT-PCR. The results showed that the application of treatment with 60 and 120 μmol/L Cd for 3 days significantly improved the biosynthesis of artemisinic acid, arteannuin B, and artemisinin...
March 2017: Frontiers of Medicine
Mingxuan Wang, Jiachen Zi, Jianhua Zhu, Shan Chen, Pu Wang, Liyan Song, Rongmin Yu
To investigate the effect of artemisinic acid (AA) on improving the production of terpenoid indole alkaloids (TIAs) of Catharanthus roseus cambial meristematic cells (CMCs), feeding AA to C. roseus CMCs caused 2.35-fold and 2.51-fold increases in the production of vindoline and catharanthine, respectively, compared with those of the untreated CMCs. qRT-PCR experiments showed that AA resulted in a 1.36-8.52 fold increase in the transcript levels of several related genes, including octadecanoid-derivative responsive Catharanthus AP2-domain protein 3 (ORCA3), tryptophan decarboxylase (TDC), strictosidine synthase (STR) and desacetoxyvindoline 4-hydroxylase (D4H)...
June 2016: Natural Product Communications
Bo Wang, Arman Beyraghdar Kashkooli, Adrienne Sallets, Hieng-Ming Ting, Norbert C A de Ruijter, Linda Olofsson, Peter Brodelius, Mathieu Pottier, Marc Boutry, Harro Bouwmeester, Alexander R van der Krol
Our lack of full understanding of transport and sequestration of the heterologous products currently limit metabolic engineering in plants for the production of high value terpenes. For instance, although all genes of the artemisinin/arteannuin B (AN/AB) biosynthesis pathway (AN-PW) from Artemisia annua have been identified, ectopic expression of these genes in Nicotiana benthamiana yielded mostly glycosylated pathway intermediates and only very little free (dihydro)artemisinic acid [(DH)AA]. Here we demonstrate that Lipid Transfer Protein 3 (AaLTP3) and the transporter Pleiotropic Drug Resistance 2 (AaPDR2) from A...
November 2016: Metabolic Engineering
Zongyou Lv, Shu Wang, Fangyuan Zhang, Lingxian Chen, Xiaolong Hao, Qifang Pan, Xueqing Fu, Ling Li, Xiaofen Sun, Kexuan Tang
The NAC (NAM, ATAF and CUC) superfamily is one of the largest plant-specific transcription factor families. NAC transcription factors always play important roles in response to various abiotic stresses. A NAC transcription factor gene AaNAC1 containing a complete open reading frame (ORF) of 864 bp was cloned from Artemisia annua. The expression of AaNAC1 could be induced by dehydration, cold, salicylic acid (SA) and methyl jasmonate (MJ), suggesting that it might be a key regulator of stress signaling pathways in A...
September 2016: Plant & Cell Physiology
Sibo Wang, Melissa J Towler, Pamela J Weathers
Roots of plants with high artemisinin-producing leaves increased leaf production of artemisinin in low-producing plants and vice versa indicating roots are involved in controlling artemisinin biosynthesis in shoots. The anti-malarial sesquiterpene, artemisinin, is produced and stored in glandular trichomes (GLTs) of Artemisia annua. Evidence suggested roots, which produce no significant artemisinin nor precursor compounds, regulate production of artemisinin biosynthesis in the leaves. Using grafting, we studied the relationship between rootstock and scion by measuring GLTs and five artemisinic metabolites (artemisinin, deoxyartemisinin, dihydroartemisinic acid, artemisinic acid, arteannuin B) in scions of ungrafted, self-grafted, and cross-grafted plants among three cultivars: S and 15 both having GLTs with artemisinin at 1...
November 2016: Planta
Nicholas Moore, Nawel Hamza, Benedicte Berke, Anwar Umar
Ethnopharmacology aims to identify new therapeutic agents based on their traditional use. It begins by the identification of disease states, and of the traditional therapies for these, most commonly herbals. Herbals of interest are selected from ethnopharmacological surveys, and tested on experimental models of the diseases of interest. Once the activity of the traditional remedy is demonstrated, including dose-dependence, if possible comparatively to reference medications, the active ingredients can be explored, if possible using bioguided extraction...
January 2017: British Journal of Clinical Pharmacology
Paulina Fuentes, Fei Zhou, Alexander Erban, Daniel Karcher, Joachim Kopka, Ralph Bock
Artemisinin-based therapies are the only effective treatment for malaria, the most devastating disease in human history. To meet the growing demand for artemisinin and make it accessible to the poorest, an inexpensive and rapidly scalable production platform is urgently needed. Here we have developed a new synthetic biology approach, combinatorial supertransformation of transplastomic recipient lines (COSTREL), and applied it to introduce the complete pathway for artemisinic acid, the precursor of artemisinin, into the high-biomass crop tobacco...
June 14, 2016: ELife
Paskorn Muangphrom, Hikaru Seki, Munenori Suzuki, Aya Komori, Mika Nishiwaki, Ryota Mikawa, Ery Odette Fukushima, Toshiya Muranaka
The production of artemisinin, the most effective antimalarial compound, is limited to Artemisia annua. Enzymes involved in artemisinin biosynthesis include amorpha-4,11-diene synthase (ADS), amorpha-4,11-diene 12-monooxygenase (CYP71AV1) and artemisinic aldehyde Δ(11)13 reductase (DBR2). Although artemisinin and its specific intermediates are not detected in other Artemisia species, we reported previously that CYP71AV1 and DBR2 homologs were expressed in some non-artemisinin-producing Artemisia plants. These homologous enzymes showed similar functions to their counterparts in A...
August 2016: Plant & Cell Physiology
Ritesh Kumar Yadav, Rajender Singh Sangwan, Avadesh K Srivastava, Neelam S Sangwan
Artemisia annua accumulates substantial quantities of unique and highly useful antimalarial sesquiternoid artemisinin and related phytomolecules as well as its characteristic essential oil in its glandular trichomes. The phytomolecules are mainly produced in its leaves and inflorescences. Artemisia annua plants were grown under NaCl salinity (50, 100 and 200 mM) stress conditions imposed throughout the entire life cycle of the plant. Results revealed that specialized metabolites like artemisinin, arteannuin-B, artemisinic acid + dihydroartemisinic acid and essential oil accumulation were positively modulated by NaCl salinity stress...
January 2017: Protoplasma
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