Correlation analysis between artemisinin and its derivative contents and trichome characteristics from different Artemisia species

Yun Ji Park1, To Quyen Truong1,2, Yeong Bin Choi1, Phuong Kim Huynh2,1, Jinyoung Moon1, Song Yi Koo3, Hyoung Seok Kim1, Sang Min Kim2,1
1Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung, Republic of Korea
2Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul, Republic of Korea
3Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Republic of Korea

Tóm tắt

Artemisia species have significant commercial, medical, and economic value and are widely used in the traditional medicine and pharmaceutical industries. Artemisinin, a powerful antimalarial agent, is an important pharmaceutical metabolite that primarily accumulates within the glandular trichomes (GTs) on the leaf surface of Artemisia plants. Trichomes arising from the elongation of epidermal cells can be classified into GTs and non-glandular trichomes (NGTs) based on their morphology. GTs and NGTs are present in Artemisia species, and the relationship between GTs and artemisinin has been extensively studied; however, the correlation between NGTs and artemisinin remains relatively unexplored. In this study, we inferred artemisinin derivatives and trichome characteristics based on the type of species, developmental stage, and leaf age and conducted correlation analyses to investigate the factors influencing artemisinin content across different Artemisia species. Artemisinin and its derivatives exhibited variations in distribution based on species and leaf age, with a decreasing trend observed across most species as the developmental stage progressed. Noticeable differences among Artemisia species were observed in leaf shape, morphology, and trichome distribution. Although the observed data did not evidently differentiate between species, developmental stage, and leaf age groups, principal component analysis revealed that artemisinin was positively associated with the NGTs density, indicating a correlation coefficient of 0.56 (p < 0.0001). Therefore, the number of NGTs may affect the artemisinin content in different Artemisia species.

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Tài liệu tham khảo

Singh P, Bajpai V, Khandelwal N, Varshney S, Gaikwad AN, Srivastava M, Singh B, Kumar B (2021) Determination of bioactive compounds of Artemisia Spp. plant extracts by LC-MS/MS technique and their in-vitro anti-adipogenic activity screening. J Pharm Biomed Anal 193:113707 da Silva JAT, Yonekura L, Kaganda J, Mookdasanit J, Nhut DT, Afach G (2005) Important secondary metabolites and essential oils of species within the Anthemideae (Asteraceae). J Herbs Spices Med Plants 11:1–46 Bora KS, Sharma A (2011) The genus Artemisia: a comprehensive review. Pharm Biol 49:101–109 Brown GD (2010) The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao). Molecules 15:7603–7698 Mannan A, Ahmed I, Arshad W, Asim MF, Qureshi RA, Hussain I, Mirza B (2010) Survey of artemisinin production by diverse Artemisia species in northern Pakistan. Malar J 9:1–9 Mutabingwa TK (2005) Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy! Acta Trop 95:305–315 Xiao L, Tan H, Zhang L (2016) Artemisia annua glandular secretory trichomes: the biofactory of antimalarial agent artemisinin. Sci Bull 61:26–36 Hassani D, Fu X, Shen Q, Khalid M, Rose JK, Tang K (2020) Parallel transcriptional regulation of artemisinin and flavonoid biosynthesis. Trends Plant Sci 25:466–476 Schilmiller AL, Last RL, Pichersky E (2008) Harnessing plant trichome biochemistry for the production of useful compounds. Plant J 54:702–711 Wu T, Wang Y, Guo D (2012) Investigation of glandular trichome proteins in Artemisia annua L. using comparative proteomics. PLoS ONE 7:41822 Werker E (2000) Trichome diversity and development. Adv Bot Res 31:1–35 Hussain A, Hayat MQ, Sahreen S, Bokhari SAI (2019) Unveiling the foliar epidermal anatomical characteristics of genus Artemisia (Asteraceae) from northeast (Gilgit-Baltistan), Pakistan. Int J Agric Biol 21:630–638 Duke MV, Paul RN, Elsohly HN, Sturtz G, Duke SO (1994) Localization of artemisinin and artemisitene in foliar tissues of glanded and glandless biotypes of Artemisia annua L. Int J Plant Sci 155:365–372 Soni R, Shankar G, Mukhopadhyay P, Gupta V (2022) A concise review on Artemisia annua L.: A major source of diverse medicinal compounds. Ind Crops Prod 184:115072 Hussain A (2020) The genus Artemisia (Asteraceae): A review on its ethnomedicinal prominence and taxonomy with emphasis on foliar anatomy, morphology, and molecular phylogeny. Proc Pak Acad Sci 57:1–28 Hayat MQ, Ashraf M, Khan MA, Yasmin G, Shaheen N, Jabeen S (2009) Diversity of foliar trichomes and their systematic implications in the genus Artemisia (Asteraceae). Int J Agric Biol 11:566–570 Salehi M, Karimzadeh G, Naghavi MR, Naghdi Badi H, Rashidi Monfared S (2018) Expression of key genes affecting artemisinin content in five Artemisia species. Sci Rep 8:12659 Maes L, Van Nieuwerburgh FC, Zhang Y, Reed DW, Pollier J, Vande Casteele SR, Inzé D, Covello PS, Deforce DL, Goossens A (2011) Dissection of the phytohormonal regulation of trichome formation and biosynthesis of the antimalarial compound artemisinin in Artemisia annua plants. New Phytol 189:176–189 Liu C, Liu S, Tse WM, Tse KWG, Erbu A, Xiong H, Lanzi G, Liu Y, Ye B (2023) A distinction between Fritillaria Cirrhosa Bulbus and Fritillaria Pallidiflora Bulbus via LC–MS/MS in conjunction with principal component analysis and hierarchical cluster analysis. Sci Rep 13:2735 Salehi M, Karimzadeh G, Naghavi MR, Badi HN, Monfared SR (2018) Expression of artemisinin biosynthesis and trichome formation genes in five Artemisia species. Ind Crops Prod 112:130–140 Lommen WJ, Elzinga S, Verstappen FW, Bouwmeester HJ (2007) Artemisinin and sesquiterpene precursors in dead and green leaves of Artemisia annua L. crops. Planta Med 73:1133–1139 Arsenault PR, Wobbe KK, Weathers PJ (2008) Recent advances in artemisinin production through heterologous expression. Curr Med Chem 15:2886–2896 Ranjbar M, Naghavi MR, Alizadeh H, Soltanloo H (2015) Expression of artemisinin biosynthesis genes in eight Artemisia species at three developmental stages. Ind Crops Prod 76:836–843 Nguyen KT, Arsenault PR, Weathers PJ (2011) Trichomes + roots + ROS = artemisinin: regulating artemisinin biosynthesis in Artemisia annua L. In Vitro Cell Dev Biol Plant 47:329–338 Ferreira JF, Janick J (1995) Floral morphology of Artemisia annua with special reference to trichomes. Int J Plant Sci 156:807–815 Telfer A, Bollman KM, Poethig RS (1997) Phase change and the regulation of trichome distribution in Arabidopsis thaliana. Development 124:645–654 Mata-Nicolás E, Montero-Pau J, Gimeno-Paez E, García-Pérez A, Ziarsolo P, Blanca J, Van der Knaap E, Díez MJ, Cañizares J (2021) Discovery of a major QTL controlling trichome IV density in tomato using K-seq genotyping. Genes 12:243 Arsenault PR, Vail D, Wobbe KK, Erickson K, Weathers PJ (2010) Reproductive development modulates gene expression and metabolite levels with possible feedback inhibition of artemisinin in Artemisia annua. Plant Physiol 154:958–968 Tellez MR, Canel C, Rimando AM, Duke SO (1999) Differential accumulation of isoprenoids in glanded and glandless Artemisia annua L. Phytochemisty 52:1035–1040 Chen M, Yan T, Shen Q, Lu X, Pan Q, Huang Y, Tang Y, Fu X, Liu M, Jiang W (2017) GLANDULAR TRICHOME-SPECIFIC WRKY 1 promotes artemisinin biosynthesis in Artemisia annua. New Phytol 214:304–316 Mukaka MM (2012) A guide to appropriate use of correlation coefficient in medical research. Malawi Med J 24:69–71 Asuero AG, Sayago A, González A (2006) The correlation coefficient: An overview. Crit Rev Anal Chem 36:41–59 Soetaert SS, Van Neste CM, Vandewoestyne ML, Head SR, Goossens A, Van Nieuwerburgh FC, Deforce DL (2013) Differential transcriptome analysis of glandular and filamentous trichomes in Artemisia annua. BMC Plant Biol 13:1–14 Judd R, Bagley MC, Li M, Zhu Y, Lei C, Yuzuak S, Ekelöf M, Pu G, Zhao X, Muddiman DC (2019) Artemisinin biosynthesis in non-glandular trichome cells of Artemisia annua. Mol Plant 12:704–714