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Quantitative metabolomics-driven elucidation of flavonoid diversity and novel quality assessment strategy in Artemisia argyi Levl. et Van germplasms

DOI: https://doi.org/10.24326/asphc.2026.5562
Submitted: 4 July 2025
Published: 13.02.2026

Abstract

This study employed quantitative metabolomics to conduct a comprehensive and systematic analysis of the diversity and accumulation patterns of flavonoid compounds in the leaves of six different genotypes of Artemisia argyi Levl. et Van (A. argyi) germplasms. The aim was to establish a metabolite-marker-based quality evaluation system and provide theoretical underpinnings for germplasm conservation and targeted development. Flavonoids were quantitatively analyzed using ultra- performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). A combination of principal component analysis (PCA) and hierarchical cluster analysis (HCA) of heatmaps was applied to reveal the disparities in metabolic profiles among different germplasms. Orthogonal partial least squares discriminant analysis (OPLS-DA) was utilized to identify differential metabolites, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the underpinnings of metabolic pathways. The findings demonstrated that a total of 76 flavonoids belonging to 11 categories were identified. Flavones (24 compounds) and flavonols (20 compounds) were the predominant classes, accounting for 57.9% of the total. Aa36 and Aa60 all displayed the highest diversity with 64 compounds. The total flavonoid content ranged from 8.70 to 14.01 μg/g, and Aa41 had the highest content. Seven flavonoids of jaceosidin, eriodictyol, eupatorin, hispidulin, chrysosplenetin, scutellarin, quercimeritrin consistently ranked among the top 10 components in six germplasms, thereby constituting the common pharmacodynamic foundation. PCA and HCA classified six germplasms into two metabolic types. Group I, composed of Aa9, Aa13, Aa36, Aa38, and Aa41, was abundant in methoxylated flavonoids. Group II, only Aa60, had a distinctive profile dominated by scutellarin, which accounted for 52.4% of the total content (34.7 μg/g). The differential metabolites were significantly enriched in the secondary metabolite biosynthesis pathway (ko01110), flavonoid biosynthesis pathway (ko00941), and flavone/flavonol biosynthesis pathway (ko00944), which uncovered the regulatory mechanisms. The seven identified core flavonoids can function as stable metabolic markers for the quality assessment of germplasms. Meanwhile, the scutellarin dominant profile of Aa60 offers a distinct resource orientation for the development of A. argyi cultivars with cardio-cerebrovascular protective functions.

References

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  19. Bsharat, O., Salama, Y., Al-Hajj, N. et al. (2025a). Chemical profiling and biological assessment of essential oil from Artemisia herba-alba. Sci. Rep., 15, 31538. https://doi.org/10.1038/s41598-025-17221-9
  20. Bsharat, O., Salama, Y., Al-Hajj, N. et al. (2025b). Chiliadenus iphionoides: from chemical profiling to anticancer, antioxidant, α-amylase, and α-glycosidase activities. PLoS One, 20(7), e0327632. https://doi.org/10.1371/journal.pone.0327632
  21. Chen, H.L., Jia, W.J., Li, H.E. et al. (2020). Scutellarin exerts anti-inflammatory effects in activated microglia/brain macrophage in cerebral ischemia and in activated BV-2 microglia through regulation of MAPKs signaling pathway. Neuromol. Med., 22(2), 264–277. https://doi.org/10.1007/s12017-019-08582-2
  22. Chen, W., Gao, Y., Xie, W. et al. (2014). Genome-wide association analyses provide genetic and biochemical insights into natural variation in rice metabolism. Nat. Genet., 46(7), 714–721. https://doi.org/10.1038/ng.3007
  23. Chen, L.L., Zhang, H.J., Chao, J. et al. (2017). Essential oil of Artemisia argyi suppresses inflammatory responses by inhibiting JAK/ STATs activation. J. Ethnopharmacol., 204, 107–117. https://doi.org/10.1016/j.jep.2017.04.017
  24. Dong, P.P., Mei, Q.X., Dai, W.B. (2016). [Comparison study on contents of total flavonoids and heavy metals and Se in folium Artemisiae Argyi from different producing areas]. Lishizhen Med. Mat. Med. Res., 27(1), 74–76. [In Chinese].
  25. Doyle, M.G.J., Mair, B.A., Sib, A. et al. (2024a). A practical guide for the preparation of C1-labeled α-amino acids using aldehyde catalysis with isotopically labeled CO2. Nat. Protoc., 19, 2147–2179. https://doi.org/10.1038/s41596-024-00974-4
  26. Doyle, M.G.J., Bsharat, O., Sib, A. et al. (2024b). Enantioselective carbon isotope exchange. J. Am. Chem. Soc. 146(28), 18804–18810. https://doi.org/10.1021/jacs.4c03685
  27. Gong, M., Lu, J.Q., Xiao, Y.S. (2019). [Determination of total flavonoids and three main aglycones in folium Artemisiae Argyi from different origins]. China Pharm., 22(5), 966–968, 975. [In Chinese].
  28. Hong, Y., He, S., Zou, Q. et al. (2023). Eupatilin alleviates inflammatory response after subarachnoid hemorrhage by inhibition of TLR4/MyD88/NF-κB axis. J. Biochem. Mol. Toxicol., 37(5), e23317. https://doi.org/10.1002/jbt.23317
  29. Li, Y., Yao, J., Han, C. et al. (2016). Quercetin, inflammation and immunity. Nutrients, 8(3), 167. https://doi.org/10.3390/nu8030167
  30. Lee, D., Kim, C.E., Park, S.Y. et al. (2018). Protective effect of Artemisia argyi and its flavonoid constituents against contrast-induced cytotoxicity by iodixanol in LLC-PK1 Cells. Int. J. Mol. Sci., 19(5), 1387. https://doi.org/10.3390/ijms19051387
  31. Liu, L.N., Tang, H.Z., Li, X.Y. (2022). [Study on the effect of quercetin on the expression of inflammatory factors in Pg-LPS-induced RAW264.7 cells based on the ROS/TXNIP/NLRP3 pathway]. Chinese Trad. Patent Med., 44(12), 4049–4052. [In Chinese].
  32. Li, F., Zhang, L., Zhang, X.X. et al. (2024). Rutin alleviates Pb-induced oxidative stress, inflammation and cell death via activating Nrf2/ARE system in SH-SY5Y cells. NeuroToxicol., 104, 1–10. https://doi.org/10.1016/j.neuro.2024.07.010

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