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However, its bioactive compounds and therapeutic mechanisms remain unknown. The main chemical composition of LGZGD was analyzed by high\u2010performance liquid chromatography\u2013mass spectrometry (HPLC\u2013MS). Furthermore, the underlying mechanisms of LGZGD against GDM were elucidated through network pharmacology and molecular docking. The therapeutic efficacy and targets of LGZGD were further confirmed via an in vitro GDM model (high glucose [HG]\u2010treated HTR\u20108\/SVneo cells). Four compounds of LGZGD, namely, cinnamaldehyde, glycyrrhizic acid, 2\u2010atractylenolide, and pachymic acid, were detected. A total of 26 targets for LGZGD treating GDM were obtained, which were mainly involved in oxidative stress and the PI3K\u2013AKT signaling pathway. The protein\u2013protein interaction (PPI) network unveiled that AKT1, TLR4, TP53, and NOS3 were hub therapeutic targets. Molecular docking showed that these targets had strong affinity with key compounds. In vitro experiments confirmed that LGZGD treatment promoted HG\u2010induced cell viability, migration, and invasion ability while inhibited the apoptosis rate and oxidative stress. Mechanically, western blot revealed that LGZGD may protect HG\u2010treated cells by activating the PI3K\u2013AKT pathway and suppressing TLR4 expression. Our study preliminarily explored the mechanism of LGZGD in GDM treatment, providing a scientific basis for the clinical application of LGZGD.<\/jats:p>","DOI":"10.1002\/bmc.6042","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T06:52:33Z","timestamp":1731480753000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lingguizhugan decoction alleviates gestational diabetes mellitus by modulating the PI3K\u2013AKT pathway and oxidative stress: Network pharmacology and experimental evidence"],"prefix":"10.1002","volume":"39","author":[{"given":"Chenyue","family":"Cao","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Department The Second Affiliated Hospital of Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology 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