{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:54:04Z","timestamp":1791132844355,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,5,31]],"date-time":"2018-05-31T00:00:00Z","timestamp":1527724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong, Macao &amp; Taiwan Science and Technology Cooperation Project","award":["2015DFM30030"],"award-info":[{"award-number":["2015DFM30030"]}]},{"name":"funding of University of Macau","award":["MYRG2016-00055-ICMS-QRCM"],"award-info":[{"award-number":["MYRG2016-00055-ICMS-QRCM"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["ZZ10-024"],"award-info":[{"award-number":["ZZ10-024"]}]},{"name":"Major New Drug Creation \u201cStudy on the Innovative Drugs of Artemisinin and its Derivatives\u201d","award":["2017ZX09101002-003-001"],"award-info":[{"award-number":["2017ZX09101002-003-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Artemisinin, which has been isolated from Artemisia annua L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the content of artemisinin in A. annua is therefore becoming an increasing research interest, as the chemical synthesis of this metabolite is not viable. Ultraviolet B and C irradiation have been reported to improve the artemisinin content in A. annua, but they are harmful to plant growth and development. Therefore, we screened other light sources to examine if they could promote artemisinin content without affecting plant growth and development. We found that red and blue light could enhance artemisinin accumulation by promoting the expression of the genes that were involved in artemisinin biosynthesis, such as amorpha-4,11-diene synthase (ADS) and cytochrome P450 monooxygenase (CYP71AV1) genes. Thus, in addition to being the main light sources for photosynthesis, red and blue light play a key role in plant secondary metabolism, and optimizing the combination of these light might allow for the productionof artemisinin-rich A. annua.<\/jats:p>","DOI":"10.3390\/molecules23061329","type":"journal-article","created":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T03:02:50Z","timestamp":1527822170000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia annua L."],"prefix":"10.3390","volume":"23","author":[{"given":"Dong","family":"Zhang","sequence":"first","affiliation":[{"name":"Artemisinin Reserch Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Shi","sequence":"additional","affiliation":[{"name":"Artemisinin Reserch Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wu","sequence":"additional","affiliation":[{"name":"Artemisinin Reserch Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-563X","authenticated-orcid":false,"given":"Tianyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xiang","sequence":"additional","affiliation":[{"name":"Artemisinin Reserch Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,31]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018, December 09). World Malaria Report 2015. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs094\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin Resistance in Plasmodium falciparum Malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_3","first-page":"572","article-title":"Advances on the study of the pharmacological effects of artemisinin and its derivatives","volume":"15","author":"Bin","year":"2010","journal-title":"Chin. J. Clin. Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/494160a","article-title":"Malaria drug made in yeast causes market ferment","volume":"494","author":"Peplow","year":"2013","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature12051","article-title":"High-level semi-synthetic production of the potent antimalarial artemisinin","volume":"496","author":"Paddon","year":"2013","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1094\/MPMI.2003.16.12.1118","article-title":"Laminarin elicits defense responses in grapevine and induces protection against Botrytis cinerea and Plasmopara viticola","volume":"16","author":"Aziz","year":"2003","journal-title":"Mol. Plant-Microbe. Interact."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1365-3040.2008.01800.x","article-title":"Heterosis in the freezing tolerance, and sugar and flavonoid contents of crosses between Arabidopsis thaliana accessions of widely varying freezing tolerance","volume":"31","author":"Korn","year":"2008","journal-title":"Plant Cell Environ."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.foodchem.2013.03.032","article-title":"Effects of UV-B irradiation on the levels of anthocyanin, rutin and radical scavenging activity of buckwheat sprouts","volume":"141","author":"Tsurunaga","year":"2013","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S1360-1385(03)00049-9","article-title":"Dissecting the phytochrome A-dependent signaling network in higher plants","volume":"8","author":"Wang","year":"2003","journal-title":"Trends Plant Sci."},{"key":"ref_10","first-page":"217","article-title":"Light-regulated transcriptional networks in higher plants","volume":"8","author":"Jiao","year":"2007","journal-title":"Genetics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.pbi.2010.07.001","article-title":"Plant hormone signaling lightens up: Integrators of light and hormones","volume":"13","author":"Lau","year":"2010","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/j.1751-1097.1993.tb02333.x","article-title":"Protection of the D1 photosystem II reaction center protein from degradation in ultraviolet radiation following adaptation of Brassica napus L. to growth in ultraviolet radiation","volume":"57","author":"Wilson","year":"1993","journal-title":"Photochem. Photobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1104\/pp.109.4.1159","article-title":"Arabidopsis mutants lacking phenolic sunscreens exhibit enhanced ultraviolet-B injury and oxidative damage","volume":"109","author":"Landrey","year":"1995","journal-title":"Plant Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1021\/jf0009910","article-title":"Stilbene content of 3 mature Vitis vinifera berries in response to UV-C elicitation","volume":"48","author":"Adrian","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1021\/jf010672o","article-title":"Stilbene compounds and stilbene synthase expression during ripening, wilting, and UV treatment in grape cv. Corvina","volume":"49","author":"Versari","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2503\/jjshs.73.193","article-title":"Induction of resveratrol biosynthesis in skins of three grape cultivars by ultraviolet irradiation","volume":"73","author":"Takayanagi","year":"2004","journal-title":"J. Jpn. Soc. Hortic. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2503\/hrj.10.249","article-title":"Effect of cultivation practices on resveratrol content in grape berry skins","volume":"10","author":"Nishikawa","year":"2011","journal-title":"Hortic. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jphotobiol.2011.09.004","article-title":"UV-B and UV-C pre-treatments induce physiological changes and artemisinin biosynthesis in Artemisia annua L.\u2014An antimalarial plant","volume":"105","author":"Rai","year":"2011","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.phytochem.2009.10.015","article-title":"Artemisinin biosynthesis in growing plants of Artemisia annua. A 13CO2 study","volume":"71","author":"Schramek","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11627-011-9343-x","article-title":"Trichomes + roots + ROS = artemisinin: Regulating artemisinin biosynthesis in Artemisia annua L.","volume":"47","author":"Nguyen","year":"2011","journal-title":"In Vitro Cell. Dev. Biol.-Plant"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11103-012-9986-y","article-title":"Trichome-specific expression of the amorpha-4,11-diene 12-hydroxylase (cyp71av1) gene, encoding a key enzyme of artemisinin biosynthesis in Artemisia annua, as reported by a promoter-GUS fusion","volume":"81","author":"Wang","year":"2013","journal-title":"Plant Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1134\/S0026893311040145","article-title":"Cloning and Characterization of Trichome Specific Promoter of cpr71av1 Gene Involved in Artemisinin Biosynthesis in Artemisia annua L.","volume":"45","author":"Wang","year":"2011","journal-title":"Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.febslet.2006.01.065","article-title":"Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin","volume":"580","author":"Teoh","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_24","first-page":"31","article-title":"Research in biosynthesis of artemisinin (in Chinese)","volume":"33","author":"Fang","year":"2015","journal-title":"Sci. Technol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/j.1744-7909.2012.01161.x","article-title":"Transcriptional regulation of plant secondary metabolism","volume":"54","author":"Yang","year":"2012","journal-title":"J. Integr. Plant Biol."},{"key":"ref_26","first-page":"1236","article-title":"Transcriptional regulation of secondary metabolite biosynthesis in plants","volume":"1829","author":"Patra","year":"2013","journal-title":"BBA-Gene Regul. Mech."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/pcp\/pcp149","article-title":"Isolation and characterization of AaWRKY1, an Artemisia annua transcription factor that regulates the amorpha-4,11-diene synthase gene, a key gene of artemisinin biosynthesis","volume":"50","author":"Ma","year":"2009","journal-title":"Plant Cell Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/nph.12207","article-title":"AaORA, a trichome-specific AP2\/ERF transcription factor of Artemisia annua, is a positive regulator in the artemisinin biosynthetic pathway and in disease resistance to Botrytis cinerea","volume":"198","author":"Lu","year":"2013","journal-title":"New Phytol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/pcp\/pcu090","article-title":"Cloning and Characterization of AabHLH1, a bHLH Transcription Factor that Positively Regulates Artemisinin Biosynthesis in Artemisia annua","volume":"55","author":"Ji","year":"2014","journal-title":"Plant Cell Physiol."},{"key":"ref_30","unstructured":"Tang, K.X., Shen, Q., Lu, X., Fu, X.Q., Yan, T.X., Sun, X.F., and Wang, G.F. (2013). Sweet Wormwood MYC2 Transcription Factor Protein Coding Sequence and Applications Thereof. (ZL201310413155.3), China Patent."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.molp.2014.12.004","article-title":"A Basic Leucine Zipper Transcription Factor, AabZIP1, Connects Abscisic Acid Signaling with Artemisinin Biosynthesis in Artemisia annua L.","volume":"8","author":"Zhang","year":"2015","journal-title":"Mol. Plant"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1146\/annurev.arplant.56.032604.144208","article-title":"Phytochrome structure and signaling mechanisms","volume":"57","author":"Rockwell","year":"2006","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1126\/science.7638620","article-title":"Association of flavin adenine dinucleotide with the Arabidopsis blue light receptor CRY1","volume":"269","author":"Lin","year":"1995","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6892","DOI":"10.1021\/bi00020a037","article-title":"Putative blue-light photoreceptors from Arabidopsis thaliana and Sinapis alba with a high degree of sequence homology to DNA photolyase contain the two photolyase cofactors but lack DNA repair activity","volume":"34","author":"Malhotra","year":"1995","journal-title":"Biochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13871","DOI":"10.1021\/bi962209o","article-title":"Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins","volume":"35","author":"Hsu","year":"1996","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18225","DOI":"10.1073\/pnas.0507187102","article-title":"A UV-B-specific signaling component orchestrates plant UV protection","volume":"102","author":"Brown","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","unstructured":"Moore, R., Clark, W.D., Kingsley, R.S., and Vodopich, D. (1995). Plant physiology and growth. Botany, Wm. C. Brown Pub. Chapter 7."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11816-010-0156-x","article-title":"Enhancement of artemisinin content by constitutive expression of the HMG-CoA reductase gene in highyielding strain of Artemisia annua L.","volume":"5","author":"Nafis","year":"2011","journal-title":"Plant Biotechnol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1093\/jxb\/erp190","article-title":"Unravelling the regulatory mechanisms that modulate the MEP pathway in higher plants","volume":"60","author":"Cordoba","year":"2009","journal-title":"J. Exp. Bot."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fpls.2017.00077","article-title":"Overexpression and Suppression of Artemisia annua 4-Hydroxy- 3-Methylbut-2-enyl Diphosphate Reductase 1 Gene (AaHDR1) Differentially Regulate Artemisinin and Terpenoid Biosynthesis","volume":"8","author":"Ma","year":"2017","journal-title":"Front. Plant Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11240-010-9775-8","article-title":"Overexpression of farnesyl pyrophosphate synthase (FPS) gene affected artemisinin content and growth of Artemisia annua L.","volume":"103","author":"Banyai","year":"2010","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_42","first-page":"64","article-title":"Over-expressing CYP71AV1 and CPR genes enhances artemisinin content in Artemisia annua L.","volume":"10","author":"Jing","year":"2008","journal-title":"J. Agric. Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/bab.1234","article-title":"Overexpression of artemisinic aldehyde \u039411(13) reductase gene-enhanced artemisinin and its relative metabolite biosynthesis in transgenic Artemisia annua L.","volume":"62","author":"Yuan","year":"2015","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/BA20080068","article-title":"Development of transgenic Artemisia annua (Chinese wormwood) plants with an enhanced content of artemisinin, an effective anti-malarial drug, by hairpin-RNA-mediated gene silencing","volume":"52","author":"Zhang","year":"2009","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/35013076","article-title":"Targeted destabilization of HY5 during light-regulated development of Arabidopsis","volume":"405","author":"Osterlund","year":"2000","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1101\/gad.1122903","article-title":"The COP1-SPA1 interaction defines a critical step in phytochrome A-mediated regulation of HY5 activity","volume":"17","author":"Saijo","year":"2003","journal-title":"Genes Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1093\/molbev\/msg088","article-title":"The basic helix-loop-helix transcription factor family in plants: A genome-wide study of protein structure and functional diversity","volume":"20","author":"Heim","year":"2003","journal-title":"Mol. Biol. Evol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1467-7652.2011.00634.x","article-title":"WRKY transcription factors: Key components in abscisic acid signalling","volume":"10","author":"Rushton","year":"2012","journal-title":"Plant Biotechnol. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1126\/science.1146281","article-title":"Transposase-derived transcription factors regulate light signaling in Arabidopsis","volume":"318","author":"Lin","year":"2007","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhang, T., Song, C., Song, L., Shang, Z., Yang, S., Zhang, D., Sun, W., Shen, Q., and Zhao, D. (2017). RNA Sequencing and Coexpression Analysis Reveal Key Genes Involved in \u03b1-Linolenic Acid Biosynthesis in Perilla frutescens Seed. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112433"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nbt.1883","article-title":"Trinity: Reconstructing a full-length transcriptome without a genome from RNA-Seq data","volume":"29","author":"Grabherr","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1093\/nar\/gkn176","article-title":"High-throughput functional annotation and data mining with the Blast2GO suite","volume":"36","author":"Terol","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1007\/s00438-015-1038-2","article-title":"Genome-wide identification and characterization of aquaporin gene family in common bean (Phaseolus vulgaris L.)","volume":"290","author":"Ariani","year":"2015","journal-title":"Mol. Genet. Genom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1093\/bioinformatics\/btr045","article-title":"PiNGO: A Cytoscape plugin to find candidate genes in biological networks","volume":"27","author":"Smoot","year":"2011","journal-title":"Bioinformatics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/6\/1329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:06:44Z","timestamp":1760195204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/6\/1329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,31]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["molecules23061329"],"URL":"https:\/\/doi.org\/10.3390\/molecules23061329","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,31]]}}}