Storage Process: A New Method Reduces the Acute Toxicity of the Essential Oil of Artemisia argyi H. Lév. & Vaniot by 40%

Abstract

Background and objectives: Artemisia argyi H. Lév. & Vaniot essential oil (AAEO) holds significant pharmacological potential, but its application is constrained by hepatotoxicity. This study aimed to investigate the feasibility of reducing AAEO’s toxicity through storage and to evaluate changes in chemical composition, toxicity, and bioactivity.

Methods: Gas chromatography-mass spectrometry was used to analyze compositional changes during storage. Zebrafish acute toxicity tests and the liver-specific transgenic zebrafish model Tg(fabp10:EGFP) were used to assess toxicity. Antimicrobial, analgesic, and antioxidant assays evaluated variations in bioactivity.

Results: Over the 150-day storage period, gas chromatography-mass spectrometry analysis identified 39 components. Zebrafish acute toxicity tests showed that the LD₅₀ of AAEO stored for 0, 30, 60, 90, 120, and 150 days were 0.10 µL·mL⁻¹, 0.10 µL·mL⁻¹, 0.10 µL·mL⁻¹, 0.11 µL·mL⁻¹, 0.13 µL·mL⁻¹, and 0.14 µL·mL⁻¹, respectively, demonstrating a 40% reduction in acute toxicity after 150 days of storage. Using the liver-specific green fluorescent transgenic Tg(fabp10:EGFP) zebrafish model, the inhibition rates of AAEO on hepatic fluorescence intensity were measured at 68.5%, 43.5%, 42.6%, 37.8%, 34.6%, and 31.9% at different time points, confirming reduced hepatotoxicity after storage. Additionally, the antioxidant and analgesic activities of AAEO were significantly enhanced (p < 0.05) after storage, while the antibacterial activity decreased (p < 0.05).

Conclusions: After storage, AAEO significantly reduces hepatotoxicity, with a 40% decrease in acute toxicity after 150 days. Meanwhile, the antioxidant and analgesic activities of AAEO increase, while its antibacterial activity decreases after storage.

Keywords

Artemisia argyi H. Lév. & Vaniot essential oil / Toxicity / Storage process / Hepatotoxicity reduction / Bioactivity changes / Zebrafish model

References

[1] Liu Y, He Y, Wang F, Xu R, Yang M, Ci Z, et al. From longevity grass to contemporary soft gold: Explore the chemical constituents, pharmacology, and toxicology of Artemisia argyi H.Lév. & vaniot essential oil. J Ethnopharmacol 2021;279:114404. doi:10.1016/j.jep.2021.114404, PMID:34246739.

[2] Chen P, Bai Q, Wu Y, Zeng Q, Song X, Guo Y, et al. The Essential Oil of Artemisia argyi H.Lév. and Vaniot Attenuates NLRP3 Inflammasome Activation in THP-1 Cells. Front Pharmacol 2021;12:712907. doi:10.3389/fphar.2021.712907, PMID:34603026.

[3] Ge YB, Wang ZG, Xiong Y, Huang XJ, Mei ZN, Hong ZG. Anti-inflammatory and blood stasis activities of essential oil extracted from Artemisia argyi leaf in animals. J Nat Med 2016; 70(3):531-538. doi:10.1007/ s11418-016-0972-6, PMID:26894818.

[4] Du K, Zheng C, Kuang Z, Sun Y, Wang Y, Li S, Meng D. Gastroprotective effect of eupatilin, a polymethoxyflavone from Artemisia argyi H.Lév. & Vaniot, in ethanol-induced gastric mucosal injury via NF- κB signaling pathway. J Ethnopharmacol 2024;318(Pt B):116986. doi:10.1016/j.jep.2023.116986, PMID:37536645.

[5] Joshi RK. Volatile composition and antimicrobial activity of the essential oil of Artemisia absinthium growing in Western Ghats region of North West Karnataka, India. Pharm Biol 2013; 51(7):888-892. doi :10.3109/13880209.2013.768676, PMID:23570523.

[6] Obistioiu D, Cristina RT, Schmerold I, Chizzola R, Stolze K, Nichita I, et al. Chemical characterization by GC-MS and in vitro activity against Candida albicans of volatile fractions prepared from Artemisia dracunculus, Artemisia abrotanum, Artemisia absinthium and Artemisia vulgaris. Chem Cent J 2014; 8(1):6. doi:10.1186/1752-153X-8-6, PMID:24475951.

[7] Wang K, Ma J, Li Y, Han Q, Yin Z, Zhou M, et al. Effects of essential oil extracted from Artemisia argyi leaf on lipid metabolism and gut microbiota in high-fat diet-fed mice. Front Nutr 2022;9:1024722. doi:10.3389/fnut.2022.1024722, PMID:36407543.

[8] Lu ST, Tang LL, Zhou LH, Lai YT, Liu LX, Duan Y. Study on the Multitarget Mechanism and Active Compounds of Essential Oil from Artemisia argyi Treating Pressure Injuries Based on Network Pharmacology. Evid Based Complement Alternat Med 2022; 2022:1019289. doi:10.1155/2022/1019289, PMID:35096100.

[9] Li Y, Tian Y, Zhong W, Wang N, Wang Y, Zhang Y, et al. Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway. Front Cell Dev Biol 2021;9:664791. doi:10.3389/fcell.2021.664791, PMID:34268303.

[10] Ding YP, Liu JY, Tian Y, Li YL, Wu MZ, Zhao ZH. Inhibitory effects of essential oil from Artemisia argyi Folium on A549 cells. Chin Tradit Pat Med 2019; 41(9):2063-2068.

[11] Zhang XY, Xue C, Li R, Chai X, Yang J, Wang YF. The variation rule of volatile components in drying, storage and processing of Artemisia Argyi Folium. Chin Med Mat 2020; 43(6):1349-1352. doi:10.13863/j.issn1001-4454.2020.06.011.

[12] Zhang N, Zhang J, Cui W, Wu D, Zhang J, Wei B, et al. Artemisia argyi H.Lév. & Vaniot essential oil induces ferroptosis in pancreatic cancer cells via up-regulation of TFR1 and depletion of γ-glutamyl cycle. Fitoterapia 2023;168:105522. doi:10.1016/j.fitote.2023.105522, PMID:37169131.

[13] Su SH, Sundhar N, Kuo WW, Lai SC, Kuo CH, Ho TJ, et al. Artemisia argyi extract induces apoptosis in human gemcitabine-resistant lung cancer cells via the PI3K/MAPK signaling pathway. J Ethnopharmacol 2022;299:115658. doi:10.1016/j.jep.2022.115658, PMID:36075273.

[14] Zhang JL, Tao L, Guan YM, Jin C, Zang ZZ, Chen LH. Promoting effect of transdermal absorption of essential oils from Chinese materia medica and problem analysis in study of topical preparations. Chin Tradit Herbal Drugs 2017; 48(24):5263-5269. doi:10.7501/j.issn.0253-2670.2017.24.031.

[15] Feng X. Research progress on the applicability of volatile oils for promoting permeability. Chin Tradit Pat Med 2013; 35(1):157-161,164.

[16] Du J, Gao R, Zhao J. The Effect of Volatile Oil from Chinese Mugwort Leaf on Human Demodecid Mites In Vitro. Acta Parasitol 2021; 66(2):615-622. doi:10.1007/s11686-020-00314-y, PMID:33394383.

[17] Luo DY, Yan ZT, Che LR, Zhu JJ, Chen B. Repellency and insecticidal activity of seven Mugwort (Artemisia argyi) essential oils against the malaria vector Anopheles sinensis. Sci Rep 2022; 12(1):5337. doi:10.1038/s41598-022-09190-0, PMID:35351963.

[18] Yang XR, Wang ZN, Jiang HL, Tian YQ, Zhang PW, Zhang ZX. The effect of Artemisia argyi essential oil on the Trichogramma ostriniae and their combined effect on the Corcyra cephalonica. Journal of Environmental Entomology 2019; 41(3):619-625. doi:10.3969/j. issn.1674-0858.2019.03.24.

[19] Qiang MJ, Cui YH, Lu XX. Study of different concentration of Argyi leaf essential oil microemulsion on the preservation of cherry. Food Ferment Ind 2020; 46(24):132-137. doi:10.13995/j.cnki.11-1802/ ts.025049.

[20] Ge LY, Li XH, Wang J. Devellopment and application of grain protectant Artemisia Argyi. Journal of Grain Storage 2010; 39(5):3-6.

[21] Wu FF, He YS, Lu JM, Li SS. Research advance of repelling function of Artemisia argyi on mosquitoes and other insects. Journal of Agriculture 2015; 5(9):96-99.

[22] He ZJ, Huang X, Lei Z. Study on bacteriostatic effect of a new hand sanitizer with Mugwort leaf. Journal of Science and Technology 2016; 26(17):264-265.

[23] Lu Z. Study on bacteriostatic effect of air freshener of volatile oil from Artemisia Argyi. Lishizhen Medicine and Materia Medica Research 2011; 22(9):2179-2180. doi:10.3969/j.issn.1008-0805.2011.09.058.

[24] Ekiert H, Klimek-Szczykutowicz M, Rzepiela A, Klin P, Szopa A. Artemisia Species with High Biological Values as a Potential Source of Medicinal and Cosmetic Raw Materials. Molecules 2022; 27(19):6427. doi:10.3390/molecules27196427, PMID:36234965.

[25] Huang W, Zhang YR, Wang H, Zhu LL, Sun R. Expermential study on the “dose-time-toxicity” relationship of single dose hepatotoxicity induced by different components from folium Artemisia Argyi in mice. Chin J Pharmacov 2011; 8(7):392-396.

[26] Cui W, Cao Q, Liu L, Yin X, Wang X, Zhao Y, et al. Artemisia Argyi essential oil ameliorates acetaminophen-induced hepatotoxicity via CYP2E1 and γ-glutamyl cycle reprogramming. Phytomedicine 2024;135:156106. doi:10.1016/j.phymed.2024.156106, PMID:39366156.

[27] Wang ZL, Zhang X, Liu SJ, Chen HP, Liu YP. Historical evolution and research status of citri reticulatae pericarpium. Chinese Archives of Traditional Chinese Medicine 2017; 35(10):2580-2584. doi:10.13193/j. issn.1673-7717.2017.10.031.

[28] Zhou T, Jiang Y, Wen L, Yang B. Characterization of polysaccharide structure in Citrus reticulate ‘Chachi’ peel during storage and their bioactivity. Carbohydr Res 2021;508:108398. doi:10.1016/j. carres.2021.108398, PMID:34274819.

[29] Fu M, Xu Y, Chen Y, Wu J, Yu Y, Zou B, et al. Evaluation of bioactive flavonoids and antioxidant activity in Pericarpium Citri Reticulatae (Citrus reticulata ‘Chachi’) during storage. Food Chem 2017; 230:649-656. doi:10.1016/j.foodchem.2017.03.098, PMID:28407962.

[30] Zheng G, Chao Y, Liu M, Yang Y, Zhang D, Wang K, et al. Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata ‘Chachi’) under different harvesting and drying conditions. J Sci Food Agric 2021; 101(8):3280-3289. doi:10.1002/jsfa.10957, PMID:33222189.

[31] Tian C, Xu H, Li J, Han Z. Characteristics and intestinal immunomodulating activities of water-soluble pectic polysaccharides from Chenpi with different storage periods. J Sci Food Agric 2018; 98(10):3752-3757. doi:10.1002/jsfa.8888, PMID:29330852.

[32] Dong JH.Study on the Scientific Connotation of Euodia rutaecarpa “the older, the better” [Dissertation]. Nanchang: Jiangxi University of Traditional Chinese Medicine; 2019. doi:10.27180/d.cnki. gjxzc.2019.000238.

[33] Yin JL, Yin CJ. Comparison of clinical efficacy of Chen Ai and Xin Ai in the treatment of lumbar disc herniation. Asia-Pacific Traditional Medicine 2014; 10(10):121-122.

[34] Liu Y, Hu Q, He YN, Jiang Y, Wu JY, Yang X, et al. Screening of Quality Markers of Antibacterial Activity of Artemisia Argyi Leaves Essential Oil Based on Spectrum-Effect Relationships. Nat Prod Res Dev 2023; 35:1017-1026,996. doi:10.16333/j.1001-6880.2023.6.011.

[35] Dong J.Antibacterial mechanism of camphor essential oil on Escherichia coli [Dissertation]. Nanchang: Nanchang University; 2020. doi:10.27232/d.cnki.gnchu.2020.003189.

[36] Xiao SS.The prediction and verification of anti-inflammation, analgesic, anti-blood stasis and anti-acne functions of borneol essential oil [Dissertation]. Wuxi: Jiangnan University; 2021. doi:10.27169/d.cnki. gwqgu.2021.001899.

[37] Wang YH.Studies of preparation of L-borneol and essential oil from the leaves of Blumea balsamifera and their antioxidant and antimicrobial activities [Dissertation]. Wuxi: Jiangnan University; 2013.

[38] Fidyt K, Fiedorowicz A, Strządała L, Szumny A. β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Cancer Med 2016; 5(10):3007-3017. doi:10.1002/ cam4.816, PMID:27696789.

[39] Segat GC, Manjavachi MN, Matias DO, Passos GF, Freitas CS, Costa R, et al. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. Neuropharmacology 2017; 125:207-219. doi:10.1016/j.neuropharm.2017.07.015, PMID:28729222.

[40] Ojha S, Javed H, Azimullah S, Haque ME. β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease. Mol Cell Biochem 2016; 418(1-2):59-70. doi:10.1007/ s11010-016-2733-y, PMID:27316720.

[41] Yeo D, Hwang SJ, Song YS, Lee HJ. Humulene Inhibits Acute Gastric Mucosal Injury by Enhancing Mucosal Integrity. Antioxidants (Basel) 2021; 10(5):761. doi:10.3390/antiox10050761, PMID:34064830.