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The use of plant extracts is of high interest in complementary medicine. Yet, extracts are multicomponent mixtures, and difficult to pinpoint their exact mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We hypothesise that network pharmacology and bioinformatics can help experimental findings depict the exact active components and mechanism of action by which they induce their effects. Additionally, the toxicity and variability can be lowered and standardised with proper encapsulation methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Here, we propose the formulation of phytoniosomes encapsulating two <jats:italic>Artemisia<\/jats:italic> species (<jats:styled-content style=\"fixed-case\"><jats:italic>Artemisia dracunculus<\/jats:italic><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>Artemisia absinthium<\/jats:italic><\/jats:styled-content>) to mitigate AGEs and their induced cell redox dysregulation in the liver. Extracts from different solvents were identified via liquid chromatography quadrupole time\u2010of\u2010flight mass spectrometry (LC\u2010Q\u2010TOF\u2010MS\/MS). Phytoniosomes were explored for their anti\u2010glycating effect and modulation of AGE\u2010induced damages in THLE\u20102 liver cells. Network pharmacology tools were used to identify possible targets and signalling pathways implicated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data demonstrated that <jats:styled-content style=\"fixed-case\"><jats:italic>A. absinthium<\/jats:italic><\/jats:styled-content> phytoniosomes had a significant anti\u2010AGE effect comparable to reference molecules and higher than <jats:styled-content style=\"fixed-case\"><jats:italic>A. dracunculus<\/jats:italic><\/jats:styled-content>. They were able to restore cell dysfunction through the restoration of tumour necrosis alpha (TNF\u2010\u03b1), interleukin 6 (IL\u20106), nitric oxide, and total antioxidant capacity. Phytoniosomes were able to protect cells from apoptosis by decreasing caspase 3 activity. Network pharmacology and bioinformatic analysis confirmed the induction of the effect via Akt\u2010PI3K\u2010MAPK and AGE\u2010RAGE signalling pathways through quercetin and luteolin actions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The current report highlights the potential of <jats:italic>Artemisia<\/jats:italic> phytoniosomes as strong contenders in AGE\u2010related disease therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pca.3159","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T02:50:56Z","timestamp":1657162256000},"page":"1058-1067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combination of LC\u2010Q\u2010TOF\u2010MS\/MS, network pharmacology, and nanoemulsion approaches identifies active compounds of two <i>Artemisia<\/i> species responsible for tackling early diabetes\u2010related metabolic complications in the liver"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-6415","authenticated-orcid":false,"given":"Hichem","family":"Moulahoum","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8541-0540","authenticated-orcid":false,"given":"Faezeh","family":"Ghorbanizamani","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Sciences Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zineb","family":"Khiari","sequence":"additional","affiliation":[{"name":"Laboratory of Ethnobotany and Natural Substances, Department of Natural Sciences Higher Normal School Kouba  Algiers Algeria"},{"name":"Laboratory of Cellular and Molecular Biology (BCM), Biochemistry &amp; Extracellular Matrix Remodelling, Faculty of Biological Sciences 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