Planta Med 2021; 87(08): 584-599
DOI: 10.1055/a-1345-9528
Biological and Pharmacological Activity
Reviews

Artemisia annua – Importance in Traditional Medicine and Current State of Knowledge on the Chemistry, Biological Activity and Possible Applications

Halina Ekiert
1   Chair and Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland
,
Joanna Świątkowska
1   Chair and Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland
,
Paweł Klin
2   Family Medicine Clinic, Medizinisches Versorgungszentrum (MVZ) Burgbernheim GmbH, Burgbernheim, Germany
,
Agnieszka Rzepiela
3   Museum of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland
,
1   Chair and Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland
› Author Affiliations
Supported by: Polish Ministry of Science and Higher Education N42/DBS/000010

Abstract

Artemisia annua (annual mugwort) is a species that has long been used in traditional Asian medicine, mainly Chinese and Hindu. The species is widespread and known as a medicinal plant not only in Asia but also in Europe, in both Americas, and Australia. The species has become a subject of particular interest due to the 2015 Nobel Prize awarded for detecting the sesquiterpene lactone artemisinin in it and proving its antimalarial activities. The raw materials obtained from this species are Artemisiae annuae folium and Artemisiae annuae herba. The leaves are a raw material in the Chinese Pharmacopoeia and Vietnamese Pharmacopoeia. Both raw materials are in the International Pharmacopoeia published by the WHO. The main components of these raw materials are mainly specific sesquiterpene lactones, essential oil, flavonoids, coumarins, and phenolic acids. In traditional Asian medicine, the species is used, for example, in the treatment of jaundice and bacterial dysentery, as an antipyretic agent in malaria and tuberculosis, in the treatment of wounds and haemorrhoids, and in viral, bacterial, and autoimmune diseases. Professional pharmacological studies conducted today have confirmed its known traditional applications and explain previously unknown mechanisms of its biological action and have also found evidence of new directions of biological activity, including, among others, anti-inflammatory, analgesic, antioxidant, antitumour, and nephroprotective activities. The species is of growing importance in the cosmetics industry.



Publication History

Received: 16 October 2020

Accepted after revision: 16 December 2020

Article published online:
22 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Efferth T, Zacchino S, Georgiev MI, Liu L, Wagner H, Panossian A. Nobel Prize for artemisinin brings phytotherapy into the spotlight. Phytomedicine 2015; 22: 1-4
  • 2 Ekiert H, Kubica P, Kwiecień I, Szopa A. Nagroda Nobla 2015 z medycyny-zwycięstwo badań z zakresu fitochemii, bakteriologii i farmakologii. Farm Pol 2016; 72: 315-326
  • 3 Aftab T, Ferreira JFS, Masroor M, Khan A, Naeem M. Artemisia annua – Pharmacology and Biotechnology. Berlin, Heidelberg: Springer Berlin Heidelberg; 2014
  • 4 Bora KS, Sharma A. The genus Artemisia: a comprehensive review. Pharm Biol 2011; 49: 101-109
  • 5 Alesaeidi S, Miraj S. A systematic review of anti-malarial properties, immunosuppressive properties, anti-inflammatory properties, and anti-cancer properties of Artemisia annua . Electron Physician 2016; 8: 3150-3155
  • 6 Das S. Artemisia annua (qinghao): a pharmacological review. Int J Pharm Sci Res 2012; 3: 4573-4577
  • 7 Brown GD. The biosynthesis of artemisinin (qinghaosu) and the phytochemistry of Artemisia annua L. (qinghao). Molecules 2010; 15: 7603-7698
  • 8 World Health Organization. WHO monograph on good agricultural and collection practices (GACP) for Artemisia annua L. Geneva: World Health Organization; 2006: 300 Accessed September 10 2020 at: https://apps.who.int/iris/bitstream/handle/10665/43509/9241594438_eng.pdf;jsessionid=A927467AFDCFEA879E90A88074766735?sequence=1
  • 9 Ding F, Ma T, Hao M, Wang Q, Chen S, Wang D, Huang L, Zhang X, Jiang D. Mapping worldwide environmental suitability for Artemisia annua L. Sustainability 2020; 12: 1309
  • 10 Editorial Committee on Flora of the Peopleʼs Republic of China of the Chinese Academy of Sciences. Flora of the Peopleʼs Republic of China. 2nd ed.. ed. Beijing: Science Press; 1991
  • 11 van Wyk BE, Wink M. Medicinal Plants of the World. Portland: Timber Press; 2004
  • 12 Willcox M. Artemisia species: From traditional medicines to modern antimalarials-and back again. J Altern Complement Med 2009; 15: 101-109
  • 13 Pellicer J, Saslis-Lagoudakis CH, Carrió E, Ernst M, Garnatje T, Grace OM, Gras A, Mumbrú M, Vallès J, Vitales D, Rønsted N. A phylogenetic road map to antimalarial Artemisia species. J Ethnopharmacol 2018; 225: 1-9
  • 14 Phuong Thao NT, Thi Thuy N, Minh Hoi T, Huy Thai T, Muselli A, Bighelli A, Castola V, Casanova J. Artemisia vulgaris L. from Vietnam: chemical variability and composition of the oil along the vegetative life of the plant. J Essent Oil Res 2004; 16: 358-361
  • 15 Nguyen T. Vietnamese Pharmacopoeia. Hanoi: Vietnamese Pharmacopoeia Commission; 2005
  • 16 Chinese Pharmacopoeia Commission. Pharmacopoeia of the Peopleʼs Republic of China. Beijing: China Chemical Industry Press; 2005
  • 17 van der Kooy F, Sullivan SE. The complexity of medicinal plants: the traditional Artemisia annua formulation, current status and future perspectives. J Ethnopharmacol 2013; 150: 1-13
  • 18 Garcia LC. A review of Artemisia annua L.: Its genetics, biochemical characteristics, and anti-malarial efficacy. Int J Sci Technol 2015; 5: 38-46
  • 19 Ryu JH, Lee SJ, Kim MJ, Shin JH, Cho KM, Sung NJ. Antioxidant and anticancer activities of Artemisia annua L. and determination of functional compounds. J Korean Soc Food Sci Nutr 2011; 40: 509-516
  • 20 Slezakova S, Ruda-Kucerova J. Anticancer activity of artemisinin and its derivatives. Anticancer Res 2017; 37: 5995-6003
  • 21 Rolta R, Salaria D, Kumar V, Sourirajan A, Dev K. Phytocompounds of Rheum emodi, Thymus serpyllum and Artemisia annua inhibit COVID-19 binding to ACE2 receptor: in silico approach. Res Sq 2020; 5: 1-23
  • 22 Law S, Leung AW, Xu C. Is the traditional Chinese herb “Artemisia annua” possible to fight against COVID-19?. Integr Med Res 2020; 9: 100474
  • 23 Dong R, Xiong X, Chen G. Discuss about the application of Artemisia annua prescriptions in the treatment of COVID-19. TMR Mod Herb Med 2020; 3: 1-2
  • 24 Kapepula PM, Kabengele JK, Kingombe M, Van Bambeke F, Tulkens PM, Sadiki Kishabongo A, Decloedt E, Zumla A, Tiberi S, Suleman F, Tshilolo L, Muyembe-TamFum JJ, Zumla A, Nachega JB. Artemisia spp. derivatives for COVID-19 treatment: anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials. Am J Trop Med Hyg 2020; 103: 960-964
  • 25 Yu J, Wang G, Jiang N. Study on the repairing effect of cosmetics containing Artemisia annua on sensitive skin. J Cosmet Dermatological Sci Appl 2020; 10: 8-19
  • 26 Missouri Botanical Garden. Accessed August 31, 2020 at: http://www.Tropicos.org
  • 27 GBIF. GBIF Home Page. https://www.gbif.org/
  • 28 The Plant List. Accessed September 1, 2020 at: http://www.theplantlist.org/
  • 29 The Herb Society of America. Artemesia: an essential Guide. 2014 Accessed September 1, 2020 at: https://www.herbsociety.org/file_download/inline/d52eae8c-be89-497d-94b3-7fc8da4105f1
  • 30 Zeb S, Ali A, Zaman W, Zeb S, Ali S, Ullah F, Shakoor A. Pharmacology, taxonomy and phytochemistry of the genus Artemisia specifically from Pakistan: a comprehensive review. Pharm Biomed Res 2019; 4: 1-12
  • 31 Ferreira J, Anick J. Annual Wormwood (Artemisia annua L.). New Crop Fact Sheet 2009. Accessed August 30, 2020 at: https://hort.purdue.edu/newcrop/CropFactSheets/artemisia.pdf
  • 32 Sudnik-Wójcikowska B. Rośliny synantropijne. Warszawa: Multico; 2011
  • 33 Tu Y. From Artemisia annua L. to Artemisinins. The Discovery and Development of Artemisinins and antimalarial Agents. London, UK: Chemical Industry Press, Elsevier Inc.; 2017
  • 34 Wąsowicz A. Occurrence of Artemisia annua L. in Wrocław city area (Lower Silesia, Poland). Bot Silesiaca 2002; 1: 141-146
  • 35 Gingade S, Varghese TS, Manivel P. Cultivation of Artemisia (Artemisia annua Linn.). Boriavi: ICAR – Directorate of medicinal and aromatic plants research, Boriavi, Anand, Gujarat; 2014
  • 36 Willcox M, Bodeker G, Rasoanaivo P, Addae-Kyereme J. Traditional medicinal Plants and Malaria. Boca Raton: CRC Press; 2004
  • 37 Verma RK, Chauhan A, Verma RS, Gupta AK. Influence of planting date on growth, artemisinin yield, seed and oil yield of Artemisia annua L. under temperate climatic conditions. Ind Crops Prod 2011; 34: 860-864
  • 38 Weathers PJ, Arsenault PR, Covello PS, McMickle A, Teoh KH, Reed DW. Artemisinin production in Artemisia annua: studies in planta and results of a novel delivery method for treating malaria and other neglected diseases. Phytochem Rev 2011; 10: 173-183
  • 39 Nafis T, Akmal M, Ram M, Alam P, Ahlawat S, Mohd A, Zainul Abdin M. Enhancement of artemisinin content by constitutive expression of the HMG-CoA reductase gene in high-yielding strain of Artemisia annua L. Plant Biotechnol Rep 2011; 5: 53-60
  • 40 Nair P, Misra A, Singh A, Shukla AK, Gupta MM, Gupta AK, Gupta V, Khanuja SP, Shasany AK. Differentially expressed genes during contrasting growth stages of Artemisia annua for artemisinin content. PLoS One 2013; 8: e60375
  • 41 Graham LA, Besser K, Blumer S, Branigan CA, Czechowski T, Elias L, Guterman I, Harvey D, Isaac PG, Khan AM, Larson TR, Li Y, Pawson T, Penfield T, Rae AM, Rathbone DA, Reid S, Ross J, Smallwood MF, Segura V, Townsend T, Vyas D, Winzer T, Bowles D. The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin. Science 2010; 327: 328-331
  • 42 Marinas IC, Oprea E, Chifiriuc MC, Badea IA, Buleandra M, Lazar V. Chemical composition and antipathogenic activity of Artemisia annua essential oil from Romania. Chem Biodivers 2015; 12: 1554-1564
  • 43 Hwang DI, Won KJ, Kim DY, Yoon SW, Park JH, Kim B, Lee HM. Anti-adipocyte differentiation activity and chemical composition of essential oil from Artemisia annua . Nat Prod Commun 2016; 11: 539-542
  • 44 Nageeb A, Al-Tawashi A, Mohammad Emwas AH, Abdel-Halim Al-Talla Z, Al-Rifai N. Comparison of Artemisia annua bioactivities between traditional medicine and chemical extracts. Curr Bioact Compd 2014; 9: 324-332
  • 45 Kumar Ashok P, Upadhyaya K. Preliminary phytochemical screening and physico-chemical parameters of Artemisia absinthium and Artemisia annua . J Pharmacogn Phytochem 2013; 1: 2668735
  • 46 Weathers PJ, Towler M, Hassanali A, Lutgen P, Engeu PO. Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries?. World J Pharmacol 2014; 3: 39-55
  • 47 Bora KS, Sharma A. The genus Artemisia: a comprehensive review. Pharm Biol 2011; 49: 101-109
  • 48 Cala AC, Ferreira JFS, Chagas ACS, Gonzalez JM, Rodrigues RA, Foglio MA, Oliveira MC, Sousa IM, Magalhães PM, Barioni Júnior W. Anthelmintic activity of Artemisia annua L. extracts in vitro and the effect of an aqueous extract and artemisinin in sheep naturally infected with gastrointestinal nematodes. Parasitol Res 2014; 113: 2345-2353
  • 49 Elfawal MA, Towler MJ, Reich NG, Golenbock D, Weathers PJ, Rich SM. Dried whole plant Artemisia annua as an antimalarial therapy. PLoS One 2012; 7: 1-7
  • 50 Akhila A, Thakur RS, Popli SP. Biosynthesis of artemisinin in Artemisia annua . Phytochemistry 1987; 26: 1927-1930
  • 51 Weathers PJ, Towler MJ. The flavonoids casticin and artemetin are poorly extracted and are unstable in an Artemisia annua tea infusion. Planta Med 2012; 78: 1024-1026
  • 52 Ferreira JFS, Luthria DL, Sasaki T, Heyerick A. Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules 2010; 15: 3135-3170
  • 53 Ko YS, Lee WS, Panchanathan R, Joo YN, Choi YH, Kim GS, Jung JM, Ryu CH, Shin SC, Kim HJ. Polyphenols from Artemisia annua L inhibit adhesion and EMT of highly metastatic breast cancer cells MDA-MB-231. Phyther Res 2016; 20: 1180-1188
  • 54 Carbonara T, Pascale R, Argentieri MP, Papadia P, Fanizzi FP, Villanova L, Avato P. Phytochemical analysis of a herbal tea from Artemisia annua L. J Pharm Biomed Anal 2012; 62: 79-86
  • 55 De Donno A, Grassi T, Idolo A, Guido M, Papadia P, Caccioppola A, Villanova L, Merendino A, Bagordo F, Fanizzi FP. First-time comparison of the in vitro antimalarial activity of Artemisia annua herbal tea and artemisinin. Trans R Soc Trop Med Hyg 2012; 106: 696-700
  • 56 Kim KE, Ko KH, Heo RW, Yi CO, Shin HJ, Kim JY, Park JH, Nam S, Kim H, Roh GS. Artemisia annua leaf extract attenuates hepatic steatosis and inflammation in high-fat diet-fed mice. J Med Food 2016; 19: 290-299
  • 57 Silva LF, Magalhães PM, Costa MR, Alecrim Md. Chaves FC, Hidalgo Ade F, Pohlit AM, Vieira PP. In vitro susceptibility of Plasmodium falciparum Welch field isolates to infusions prepared from Artemisia annua L. cultivated in the Brazilian Amazon. Mem Inst Oswaldo Cruz 2012; 107: 859-866
  • 58 Tang C, Zhao Y, Huang S, Jin Y, Liu J, Luo J, Zheng J, Shi D. Influence of Artemisia annua extract derivatives on proliferation, apoptosis and metastasis of osteosarcoma cells. Pak J Pharm Sci 2015; 28: 773-779
  • 59 Melillo de Magalhães P, Dupont I, Hendrickx A, Joly A, Raas T, Dessy S, Sergent T, Schneider YJ. Anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cells. Food Chem 2012; 134: 864-871
  • 60 Phadungrakwittaya R, Chotewuttakorn S, Piwtong M, Thamsermsang O, Laohapand T, Akarasereenont P. Identification of apigenin and luteolin in Artemisia annua L. for the quality control. Siriraj Med J 2019; 71: 240-245
  • 61 Han J, Ye M, Qiao X, Xu M, Wang BR, Guo DA. Characterization of phenolic compounds in the Chinese herbal drug Artemisia annua by liquid chromatography coupled to electrospray ionization mass spectrometry. J Pharm Biomed Anal 2008; 47: 516-525
  • 62 Engeu PO, Omujal F, Agwaya M, Kyakulaga H, Obua C. Variations in antimalarial components of Artemisia annua Linn. from three regions of Uganda. Afr Health Sci 2015; 15: 828-834
  • 63 Abid Ali Khan MM, Jain DC, Bhakuni RS, Zaim M, Thakur RS. Occurrence of some antiviral sterols in Artemisia annua . Plant Sci 1991; 75: 161-165
  • 64 Kazemi M. Essential oil of the aerial parts of Artemisia annua (Asteraceae) from Iran. J Essent Oil Bearing Plants 2015; 18: 1003-1005
  • 65 Singh ND, Kumar S, Daniell H. Expression of β-glucosidase increases trichome density and artemisinin content in transgenic Artemisia annua plants. Plant Biotechnol J 2016; 14: 1034-1045
  • 66 Brisibe EA, Umoren UE, Brisibe F, Magalhäes PM, Ferreira JFS, Luthria D, Wu X, Prior RL. Nutritional characterisation and antioxidant capacity of different tissues of Artemisia annua L. Food Chem 2009; 115: 1240-1246
  • 67 Donato R, Santomauro F, Bilia AR, Flamini G, Sacco C. Antibacterial activity of Tuscan Artemisia annua essential oil and its major components against some foodborne pathogens. LWT – Food Sci Technol 2015; 64: 1251-1254
  • 68 Radulović NS, Randjelović PJ, Stojanović NM, Blagojević PD, Stojanović-Radić ZZ, Ilić IR, Djordjević VB. Toxic essential oils. Part II: Chemical, toxicological, pharmacological and microbiological profiles of Artemisia annua L. volatiles. Food Chem Toxicol 2013; 58: 37-49
  • 69 Cafferata LFR, Gatti WO, Mijailosky S. Secondary gaseous metabolites analyses of wild Artemisia annua L. Molec Med Chem 2010; 21: 48-52
  • 70 Yan T, Chen M, Shen Q, Li L, Fu X, Pan Q, Tang Y, Shi P, Lv Z, Jiang W, Ma YN, Hao X, Sun X, Tang K. Homeodomain protein 1 is required for jasmonate-mediated glandular trichome initiation in Artemisia annua . New Phytol 2017; 213: 1145-1155
  • 71 Efferth T, Zacchino S, Georgiev MI, Liu L, Wagner H, Panossian A. Nobel Prize for artemisinin brings phytotherapy into the spotlight. Phytomedicine 2015; 22: A1-A3
  • 72 Golenser J, Waknine JH, Krugliak M, Hunt NH, Grau GE. Current perspectives on the mechanism of action of artemisinins. Int J Parasitol 2006; 36: 1427-1441
  • 73 Długońska H. The Nobel Prize 2015 in physiology or medicine for highly effective antiparasitic drugs. Ann Parasitol 2015; 61: 299-301
  • 74 Singh Bhakuni R, Singh T, Prakash Kahol A, Amit T, Sundeep T, Tandon S, Preet Singh Khanuja S. Single pot conversion of artemisinin into artemether. 2002 Accessed September 2, 2020 at: https://patents.google.com/patent/US6683193B2/en
  • 75 Ching FM. Chinese Herbal Drug Research Trends – Felix M. Ching. New York: Nova Biomedical Book; 2007
  • 76 Unschuld PU. Medicine in China: A History of Pharmaceutics. Los Angeles, London: University of California Press Berkeley; 1986
  • 77 Riddle J. Goddesses, Elixirs, and Witches: Plants and Sexuality throughout human History. New York: Elsevier Inc.; 2010
  • 78 Błaszczak T. Podstawy medycyny chińskiej. Kraków: Proherba; 2012
  • 79 Neill US. From branch to bedside: Youyou Tu is awarded the 2011 Lasker DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria. J Clin Invest 2011; 121: 2768-3773
  • 80 Mueller MS, Karhagomba IB, Hirt HM, Wemakor E. The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics: agricultural, chemical and clinical aspects. J Ethnopharmacol 2000; 73: 487-493
  • 81 Zhang YX, Sun HX. Immunosuppressive effect of ethanol extract of Artemisia annua on specific antibody and cellular responses of mice against ovalbumin. Immunopharmacol Immunotoxicol 2009; 31: 625-630
  • 82 Ram S. Research output on Artemisia (Artemisia annua): a bibliometric study. Ann Libr Inf Stud 2011; 58: 237-248
  • 83 Sadiq A, Hayat MQ, Ashraf M. Ethnopharmacology of Artemisia annua L.: a Review. In: Aftab T, Ferreira JFS, Khan MMA, Naeem M. Artemisia Annua – Pharmacology and Biotechnology. Berlin, Heidelberg: Springer Berlin Heidelberg; 2014: 9-25
  • 84 World Health Organization. Guidelines for the Treatment Malaria, 3rd Edition. Accessed September 11, 2020 at: https://www.who.int/publications/i/item/9789241549127
  • 85 Chrubasik C, Jacobson RL. The development of artemisinin resistance in malaria: reasons and solutions. Phyther Res 2010; 24: 1104-1106
  • 86 Byakika-Kibwika P, Lamorde M, Mayanja-Kizza H, Khoo S, Merry C, Van Geertruyden JP. Artemether-lumefantrine combination therapy for treatment of uncomplicated malaria: the potential for complex interactions with antiretroviral drugs in HIV-infected individuals. Malar Res Treat 2011; 2011: 1-5
  • 87 Mueller MS, Runyambo N, Wagner I, Borrmann S, Dietz K, Heide L. Randomized controlled trial of a traditional preparation of Artemisia annua L. (annual wormwood) in the treatment of malaria. Trans R Soc Trop Med Hyg 2004; 98: 318-321
  • 88 Zime-Diawara H, Ganfon H, Gbaguidi FA, Gbaguidi F, Yemoa A, Bero J, Jansen O, Evrard B, Moudachirou M, Frederich M, Quetin-Leclercq J. The antimalarial action of aqueous and hydro alcoholic extracts of Artemisia annua L. cultivated in Benin: in vitro and in vivo studies. JAPS 2015; 7: 817-823
  • 89 Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, OʼNeill PM, Bray PG, Ward SA, Krishna S. Artemisinins target the SERCA of Plasmodium falciparum . Nature 2003; 424: 957-961
  • 90 Islamuddin M, Farooque A, Dwarakanath BS, Sahal D, Afrin F. Extracts of Artemisia annua leaves and seeds mediate programmed cell death in Leishmania donovani . J Med Microbiol 2012; 61: 1709-1718
  • 91 Noori S, Naderi GA, Hassan ZM, Habibi Z, Bathaie SZ, Hashemi SM. Immunosuppressive activity of a molecule isolated from Artemisia annua on DTH responses compared with cyclosporin A. Int Immunopharmacol 2004; 4: 1301-1306
  • 92 Stebbings S, Beattie E, McNamara D, Hunt S. A pilot randomized, placebo-controlled clinical trial to investigate the efficacy and safety of an extract of Artemisia annua administered over 12 weeks, for managing pain, stiffness, and functional limitation associated with osteoarthritis of the hip and knee. Clin Rheumatol 2016; 35: 1829-1836
  • 93 Iqbal S, Younas U, Chan KW, Zia-Ul-Haq M, Ismail M. Chemical composition of Artemisia annua L. leaves and antioxidant potential of extracts as a function of extraction solvents. Molecules 2012; 17: 6020-6032
  • 94 Michaelsen FW, Saeed MEM, Schwarzkopf J, Efferth T. Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma. Phytomedicine 2015; 22: 1223-1231
  • 95 Derda M, Hadaś E, Cholewiński M, Skrzypczak Ł, Grzondziel A, Wojtkowiak-Giera A. Artemisia annua L. as a plant with potential use in the treatment of acanthamoebiasis. Parasitol Res 2016; 115: 1635-1639
  • 96 Grajek W, Olejnik A, Stanaszek K. Kultury komórkowe nabłonka jelitowego jako model do badania transportu trans nabłonkowego. Biotechnologia 2006; 2: 148-165
  • 97 Pieniążek M, Donizy P, Ziętek M, Szynglarewicz B, Matkowski R. The role of TGF-β-related signal transduction pathways in pathogenesis of epithelial-mesenchymal transition as a key element in cancer development and progression. Postepy Hig Med Dosw 2012; 66: 583-591
  • 98 European Commission Cosing. Cosing – Cosmetics Database. Accessed September 15, 2020 at: https://ec.europa.eu/growth/sectors/cosmetics/cosing_en
  • 99 Leng X, Ye ST. An investigation on in vivo allergenicity of Artemisia annua leaves and stems. Asian Pac J Allergy Immunol 1987; 5: 125-128
  • 100 Tang R, Sun JL, Yin J, Li Z. Artemisia allergy research in China. Biomed Res Int 2015; 2015: 179426
  • 101 Taylor WRJ, White NJ. Antimalarial drug toxicity: a review. Drug Saf 2004; 27: 25-61
  • 102 McIntosh H, Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database Syst Rev 2000; (1999): CD000256
  • 103 European Food Safety Authority. Compendium of botanicals reported to contain naturally occuring substances of possible concern for human health when used in food and food supplements. EFSA J 2012; 10: 2663