{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:55:13Z","timestamp":1784868913914,"version":"3.55.0"},"reference-count":27,"publisher":"Baishideng Publishing Group Inc.","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"BACKGROUND<\/jats:p>\n Alcoholic liver disease (ALD) is driven by oxidative stress, lipid metabolism, inflammation, and apoptosis. Current therapies lack efficacy in targeting multi-pathway mechanisms. Xing-Pi-Qing-Gan decoction (XPQG) is an improved traditional Chinese medicine designed to alleviate ALD, but its molecular mechanism remains unknown.<\/jats:p>\n AIM<\/jats:p>\n To illustrate the therapeutic targets and molecular pathways of XPQG for the treatment of ALD by integrating chemical profiling, network pharmacology, transcriptomics, and experimental verification in vivo and in vitro .<\/jats:p>\n METHODS<\/jats:p>\n The components of XPQG were analyzed using ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Then, the protective effect of XPQG on ethanol-induced liver injury, especially its regulatory effect on DDIT3 expression and associated Nrf2 \/HO-1 antioxidant signaling, was investigated through in vivo animal experiments and in vitro cell experiments. A mouse model of ALD was developed, and the mechanism of XPQG was validated through hematoxylin and eosin (H&E) staining, Western blot, and quantitative RT-PCR. In addition, the key role of DDIT3 in XPQG-mediated protection was further verified by siDDIT3 cell transfection technology. Animal experiments with the reactive oxygen species inhibitor N-acetylcysteine (NAC) further validated the mechanism of XPQG to alleviate liver injury by regulating oxidative stress.<\/jats:p>\n RESULTS<\/jats:p>\n In ethanol-treated HepG2 cells, XPQG dose-dependently reduced the formation of lipid droplets, inhibited the expression of tumor necrosis factor-\u03b1, interleukin-6, interleukin-1\u03b2, and alleviated oxidative stress. In mice, XPQG (15.2 g\/kg) lowered the liver\/body weight ratio, alanine aminotransferase, aspartate aminotransferase, \u03b3-glutamyl transferase; H&E and Oil Red O demonstrated a reduction in steatosis. Network pharmacology and RNA-seq converged on MAPK signaling, suggesting DDIT3 as a likely key effector in XPQG-mediated protection. DDIT3 knockdown in HepG2 cells attenuated the benefits of XPQG, supporting DDIT3 as a critical effector mechanism in XPQG-mediated protection. The use of NAC further illustrates the correlation of drugs to oxidative stress in disease effects.<\/jats:p>\n CONCLUSION<\/jats:p>\n In summary, the results of the study suggest that XPQG is effective in improving ethanol-induced acute liver injury (ALD). Its mechanism involves the suppression of DDIT3 and the enhancement of Nrf2 \/HO-1 pathway activity.<\/jats:p>","DOI":"10.3748\/wjg.v32.i8.115077","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:45:52Z","timestamp":1770695152000},"source":"Crossref","is-referenced-by-count":1,"title":["Xing-Pi-Qing-Gan decoction alleviates alcoholic liver disease by down-regulating\n DDIT3<\/i>\n and restoring\n Nrf2<\/i>\n \/\n HO-1<\/i>\n antioxidant signaling: Multi-omics and experimental evidence"],"prefix":"10.3748","volume":"32","author":[{"given":"Na-Fei","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Feng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2018.09.006"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04166-8"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.09.002"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112712"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.469"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002572"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.915535"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6410"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI176345"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-05061-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B2200612"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2022.111259"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.06.024"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118840"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113497"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-00985-x"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003732"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.04.017"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2007.09.004"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.119118"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108543"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/jcp-2023-208963"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2023.112946"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-80066-x"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084285"}],"container-title":["World Journal of Gastroenterology"],"original-title":[],"link":[{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v32\/i8\/115077.htm","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v32\/i8\/115077.htm","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:46:06Z","timestamp":1770695166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v32\/i8\/115077.htm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":27,"journal-issue":{"issue":"8"},"alternative-id":["115077"],"URL":"https:\/\/doi.org\/10.3748\/wjg.v32.i8.115077","relation":{},"ISSN":["1007-9327"],"issn-type":[{"value":"1007-9327","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2,28]]}}}