{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T16:15:11Z","timestamp":1760890511601,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2018VFA0900100","32100027","KQTD20180413181837372"],"award-info":[{"award-number":["2018VFA0900100","32100027","KQTD20180413181837372"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018VFA0900100","32100027","KQTD20180413181837372"],"award-info":[{"award-number":["2018VFA0900100","32100027","KQTD20180413181837372"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["2018VFA0900100","32100027","KQTD20180413181837372"],"award-info":[{"award-number":["2018VFA0900100","32100027","KQTD20180413181837372"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Artemisinin (ART) is an endoperoxide molecule derived from the medicinal plant Artemisia annua L. and is clinically used as an antimalarial drug. As a secondary metabolite, the benefit of ART production to the host plant and the possible associated mechanism are not understood. It has previously been reported that Artemisia annua L. extract or ART can inhibit both insect feeding behaviors and growth; however, it is not known whether these effects are independent of each other, i.e., if growth inhibition is a direct outcome of the drug\u2019s antifeeding activity. Using the lab model organism Drosophila melanogaster, we demonstrated that ART repels the feeding of larvae. Nevertheless, feeding inhibition was insufficient to explain its toxicity on fly larval growth. We revealed that ART provoked a strong and instant depolarization when applied to isolated mitochondria from Drosophila while exerting little effect on mitochondria isolated from mice tissues. Thus, ART benefits its host plant through two distinct activities on the insect: a feeding-repelling action and a potent anti-mitochondrial action which may underlie its insect inhibitory activities.<\/jats:p>","DOI":"10.3390\/ijms24086912","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:26:06Z","timestamp":1681097166000},"page":"6912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-Mitochondrial and Insecticidal Effects of Artemisinin against Drosophila melanogaster"],"prefix":"10.3390","volume":"24","author":[{"given":"Mengjiao","family":"Zhong","sequence":"first","affiliation":[{"name":"School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6585-9284","authenticated-orcid":false,"given":"Bing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10210","DOI":"10.1002\/anie.201601967","article-title":"Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture)","volume":"55","author":"Tu","year":"2016","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2471","article-title":"The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine","volume":"17","author":"Tu","year":"2011","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s11427-015-4955-8","article-title":"Artemisinin (Qinghaosu): A mesmerizing drug that still puzzles","volume":"58","author":"Zhou","year":"2015","journal-title":"Sci. China Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Huang, M., Cao, X., Jiang, Y., Shi, Y., Ma, Y., Hu, D., and Song, X. (2022). Evaluation of the Combined Effect of Artemisinin and Ferroptosis Inducer RSL3 against Toxoplasma gondii. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010229"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102218","DOI":"10.1016\/j.parint.2020.102218","article-title":"Leishmania amazonensis response to artemisinin and derivatives","volume":"80","author":"Machin","year":"2021","journal-title":"Parasitol. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1128\/AAC.00452-09","article-title":"Combination chemotherapy against Clonorchis sinensis: Experiments with artemether, artesunate, OZ78, praziquantel, and tribendimidine in a rat model","volume":"53","author":"Keiser","year":"2009","journal-title":"Antimicrob. Agents. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15058","DOI":"10.3390\/molecules190915058","article-title":"New uses for old drugs: The tale of artemisinin derivatives in the elimination of Schistosomiasis japonica in China","volume":"19","author":"Liu","year":"2014","journal-title":"Molecules"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1039\/B816679J","article-title":"Artemisinin and its derivatives: A novel class of anti-malarial and anti-cancer agents","volume":"39","author":"Chaturvedi","year":"2010","journal-title":"Chem. Soc. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.pharmthera.2013.12.001","article-title":"Artemisinins: Pharmacological actions beyond anti-malarial","volume":"142","author":"Ho","year":"2014","journal-title":"Pharm. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1086\/591195","article-title":"The antiviral activities of artemisinin and artesunate","volume":"47","author":"Efferth","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.biotechadv.2018.01.001","article-title":"Beyond malaria: The inhibition of viruses by artemisinin-type compounds","volume":"36","author":"Efferth","year":"2018","journal-title":"Biotechnol. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.3109\/13880209.2010.528433","article-title":"Artemisia annua extracts, artemisinin and 1,8-cineole, prevent fruit infestation by a major, cosmopolitan pest of apples","volume":"49","author":"Durden","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_13","first-page":"9593","article-title":"Controlling bruchid pests of stored cowpea seeds with dried leaves of Artemisia annua and two other common botanicals","volume":"10","author":"Brisibe","year":"2011","journal-title":"Afr. J. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2478\/v10045-010-0014-4","article-title":"A study on the toxicity of a medicinal plant, Artemisia annua L.(Asteracea) extracts to the sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae)","volume":"50","author":"Zibaee","year":"2010","journal-title":"J. Plant Prot. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1007\/s10886-005-5795-y","article-title":"Laboratory evaluation of Artemisia annua L. extract and artemisinin activity against Epilachna paenulata and Spodoptera eridania","volume":"31","author":"Maggi","year":"2005","journal-title":"J. Chem. Ecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.pestbp.2010.12.009","article-title":"The effects of Artemisia annua L. and Achillea millefolium L. crude leaf extracts on the toxicity, development, feeding efficiency and chemical activities of small cabbage Pieris rapae L. (Lepidoptera: Pieridae)","volume":"99","author":"Hasheminia","year":"2011","journal-title":"Pestic. Biochem Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1603\/0022-0493-93.1.43","article-title":"Repellency and toxicity of oil from Artemisia annua to certain stored-product beetles","volume":"93","author":"Tripathi","year":"2000","journal-title":"J. Econ. Entomol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pestbp.2008.01.003","article-title":"Effects of Artemisia annua L. (Asteracea) on nutritional physiology and enzyme activities of elm leaf beetle, Xanthogaleruca luteola Mull. (Coleoptera: Chrysomellidae)","volume":"91","author":"Shekari","year":"2008","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109988","DOI":"10.1016\/j.ecoenv.2019.109988","article-title":"Bioactivity and efficacy of essential oils extracted from Artemisia annua against Tribolium casteneum (Herbst. 1797) (Coleoptera: Tenebrionidae): An eco-friendly approach","volume":"189","author":"Deb","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s10886-014-0384-6","article-title":"Potential ecological roles of artemisinin produced by Artemisia annua L.","volume":"40","author":"Duke","year":"2014","journal-title":"J. Chem. Ecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4172\/2155-6202.1000105","article-title":"Effect of Artemisia annua L.(Asterales: Asteraceae) Essential Oil on Mortality, Development, Reproduction and Energy Reserves of Plodia Interpunctella (Hubner). (Lepidoptera: Pyralidae)","volume":"2","author":"Zamani","year":"2011","journal-title":"J. Biofertil. Biopestici."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/ps\/76.8.1156","article-title":"Effects of components of Artemisia annua on coccidia infections in chickens","volume":"76","author":"Allen","year":"1997","journal-title":"Poult. Sci."},{"key":"ref_23","first-page":"11","article-title":"Effects of biochemicals of Artemisia annua in plants","volume":"21","author":"Paramanik","year":"2008","journal-title":"J. Phytol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10522-015-9624-6","article-title":"Context- and dose-dependent modulatory effects of naringenin on survival and development of Drosophila melanogaster","volume":"17","author":"Chattopadhyay","year":"2016","journal-title":"Biogerontology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s00253-011-3236-0","article-title":"Basidiomycete Clitocybe nebularis is rich in lectins with insecticidal activities","volume":"91","author":"Pohleven","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s10522-013-9487-7","article-title":"Korean mistletoe (Viscum album coloratum) extract extends the lifespan of nematodes and fruit flies","volume":"15","author":"Lee","year":"2014","journal-title":"Biogerontology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.15698\/mic2015.01.181","article-title":"Two distinct and competitive pathways confer the cellcidal actions of artemisinins","volume":"2","author":"Sun","year":"2015","journal-title":"Microb. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/jac\/dkt486","article-title":"Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides involves ROS-dependent depolarization of the membrane potential","volume":"69","author":"Antoine","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, J., Huang, L., Li, J., Fan, Q., Long, Y., Li, Y., and Zhou, B. (2010). Artemisinin directly targets malarial mitochondria through its specific mitochondrial activation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009582"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"196","DOI":"10.15698\/mic2016.05.498","article-title":"The molecular and cellular action properties of artemisinins: What has yeast told us?","volume":"3","author":"Sun","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1017\/S0043174500060458","article-title":"Artemisinin, a constituent of annual wormwood (Artemisia annua), is a selective phytotoxin","volume":"35","author":"Duke","year":"1987","journal-title":"Weed Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"PJ91","DOI":"10.1055\/s-0029-1234896","article-title":"Chemical composition of Iranian Artemisia annua L. essential oil and its antibacterial, antifungal and antioxidant effects","volume":"75","author":"Emadi","year":"2009","journal-title":"Planta. Med."},{"key":"ref_33","first-page":"229","article-title":"Chemical composition and antifungal activity of the essential oil of Artemisia annua L. against foliar and soil-borne fungal pathogens","volume":"112","author":"Soylu","year":"2005","journal-title":"Z. Pflanzenkrankh. Pflanzenschutz. J. Plant Dis. Prot."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00436-009-1651-2","article-title":"Insecticidal activity of essential oils from native medicinal plants of Central Argentina against the house fly, Musca domestica (L.)","volume":"106","author":"Palacios","year":"2009","journal-title":"Parasitol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1017\/S0043174500089001","article-title":"Allelopathic activity of annual wormwood (Artemisia annua) and the role of artemisinin","volume":"45","author":"Lydon","year":"1997","journal-title":"Weed Sci."},{"key":"ref_36","first-page":"317","article-title":"Herbicidal potential of artemisinin and allelopathic properties of Artemisia annua L.: From the laboratory to the field","volume":"21","author":"Delabays","year":"2008","journal-title":"J. Plant Dis. Prot."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1007\/BF01020500","article-title":"Plant growth regulatory activities of artemisinin and its related compounds","volume":"16","author":"Chen","year":"1990","journal-title":"J. Chem. Ecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.chemosphere.2012.05.009","article-title":"Isolation and identification of an anti-algal compound from Artemisia annua and mechanisms of inhibitory effect on algae","volume":"88","author":"Ni","year":"2012","journal-title":"Chemosphere"},{"key":"ref_39","first-page":"67","article-title":"The influence of distribution of antimalarial constituents in Artemisia annua L. on time and method of harvest","volume":"390","author":"Laughlin","year":"1995","journal-title":"Int. Soc. Hortic. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1086\/297304","article-title":"Floral Morphology of Artemisia annua with Special Reference to Trichomes","volume":"156","author":"Jorge","year":"1995","journal-title":"Int. J. Plant Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11101-010-9166-0","article-title":"Artemisinin production in Artemisia annua: Studies in planta and results of a novel delivery method for treating malaria and other neglected diseases","volume":"10","author":"Weathers","year":"2011","journal-title":"Phytochem. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7603","DOI":"10.3390\/molecules15117603","article-title":"The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao)","volume":"15","author":"Brown","year":"2010","journal-title":"Molecules"},{"key":"ref_43","unstructured":"Janick, J. (1996). Progress in New Crops, ASHS Press."},{"key":"ref_44","first-page":"203","article-title":"Selection and breeding for high artemisinin (qinghaosu) yielding strains of Artemisia annua","volume":"303","author":"Delabays","year":"1993","journal-title":"Int. Soc. Hortic. Sci. ISHS"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, W., Mo, W., Shen, D., Sun, L., Wang, J., Lu, S., Gitschier, J.M., and Zhou, B. (2005). Yeast model uncovers dual roles of mitochondria in action of artemisinin. PLoS Genet, 1.","DOI":"10.1371\/journal.pgen.0010036"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.3390\/molecules15031378","article-title":"Biological actions of artemisinin: Insights from medicinal chemistry studies","volume":"15","author":"Li","year":"2010","journal-title":"Molecules"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, X., and Zhou, B. (2023). Zinc Protoporphyrin-9 Potentiates the Anticancer Activity of Dihydroartemisinin. Antioxidants, 12.","DOI":"10.3390\/antiox12020250"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"El-Keredy, A., Schleyer, M., Konig, C., Ekim, A., and Gerber, B. (2012). Behavioural analyses of quinine processing in choice, feeding and learning of larval Drosophila. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040525"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0891-5849(03)00464-7","article-title":"Superoxide and hydrogen peroxide production by Drosophila mi-tochondria","volume":"35","author":"Miwa","year":"2003","journal-title":"Free. Radic. Biol. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6912\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:15Z","timestamp":1760123535000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6912"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24086912"],"URL":"https:\/\/doi.org\/10.3390\/ijms24086912","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,4,7]]}}}