{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:31:26Z","timestamp":1774344686602,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Chongqing Municipality","award":["cstc2021jcyj-msxmX0365"],"award-info":[{"award-number":["cstc2021jcyj-msxmX0365"]}]},{"name":"Science and Technology Research Program of the Chongqing Municipal Education Commission","award":["KJZD-K202215101"],"award-info":[{"award-number":["KJZD-K202215101"]}]},{"name":"Science and Technology Research Program of the Chongqing Municipal Education Commission","award":["KJZD-M202515104"],"award-info":[{"award-number":["KJZD-M202515104"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2025M783952"],"award-info":[{"award-number":["2025M783952"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Joint Research Fund for Technological Innovation by Chongqing Bishan District Bureau of Science and Technology and Chongqing University of Chinese Medicine","award":["BSZYYLH010"],"award-info":[{"award-number":["BSZYYLH010"]}]},{"name":"Sichuan\u2013Chongqing Collaborative Innovation Science and Technology Project funded by the Sichuan Provincial Department of Science and Technology","award":["2024YFHZ0083"],"award-info":[{"award-number":["2024YFHZ0083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Cytokine storm is a central pathogenic mechanism underlying sepsis-induced acute lung injury (SALI) and severe coronavirus disease 2019 (COVID-19), yet effective therapeutic strategies remain limited. Eupatorium lindleyanum DC. (EL), a traditional Chinese medicinal herb, has been reported to possess anti-inflammatory, antioxidant, and antiviral-related activities; however, its protective mechanisms in SALI and virus-associated inflammatory lung injury remain incompletely understood. In this study, an integrated strategy combining computational prediction and experimental validation was employed to investigate the therapeutic potential and underlying mechanisms of EL. The chemical constituents of EL were characterized by UPLC\u2013Q\u2013TOF\/MS, followed by network pharmacology, molecular docking, and molecular dynamics analyses to predict key targets and signaling pathways. A cecal ligation and puncture (CLP)-induced SALI rat model was used to evaluate lung histopathology, pulmonary edema, cytokine production, and inflammatory signaling activation. In parallel, LPS-stimulated RAW264.7 macrophages were used to assess cytokine secretion and pathway regulation in vitro. In addition, a SARS-CoV-2 pseudovirus-induced mouse model was employed to further evaluate the in vivo relevance of the representative bioactive compound hyperoside in pseudovirus-associated lung injury. A total of 32 active compounds and 697 putative targets were identified, among which 116 were associated with sepsis and COVID-19. In vivo, EL markedly alleviated lung injury, reduced the lung coefficient and wet\/dry ratio, and suppressed excessive production of proinflammatory cytokines and activation of key signaling proteins. In vitro, EL dose-dependently inhibited TNF-\u03b1 and IL-6 secretion and regulated the PI3K\u2013Akt and NF-\u03baB signaling pathways. Notably, hyperoside showed favorable predicted interactions with PI3K\u2013Akt pathway-related targets (EGFR, PI3K, and Akt), while molecular dynamics simulations supported stable interactions with several COVID-19-related targets, including ACE2, Mpro, and RdRp. Furthermore, hyperoside significantly alleviated SARS-CoV-2 pseudovirus-associated lung injury, reduced ACE2 protein expression, and downregulated EGFR, PI3K, and Akt mRNA levels in vivo. Collectively, these findings indicate that EL exerts protective effects through multi-component, multi-target, and multi-pathway mechanisms, and support its potential value for further investigation in SALI and virus-associated inflammatory lung injury.<\/jats:p>","DOI":"10.3390\/cimb48030333","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:59:36Z","timestamp":1774267176000},"page":"333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eupatorium lindleyanum DC. Suppresses Cytokine Storm by Inhibiting NF-\u03baB and PI3K\u2013Akt Signaling in Sepsis-Associated and Virus-Related Acute Lung Injury"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3954-4406","authenticated-orcid":false,"given":"Chen","family":"Luo","sequence":"first","affiliation":[{"name":"College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China"},{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peilin","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Xia","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daike","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiduo","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7634-054X","authenticated-orcid":false,"given":"Junjie","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Jing","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianqin","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China"},{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S2213-2600(23)00330-2","article-title":"Profiling the dysregulated immune response in sepsis: Overcoming challenges to achieve the goal of precision medicine","volume":"12","author":"Cajander","year":"2024","journal-title":"Lancet Respir. 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