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This study integrated network pharmacology, molecular docking, in vitro pharmacodynamics and HPLC-based fingerprint and quality evaluation to elucidate SSP\u2019s anti-influenza mechanisms and optimize its fermentation process. Network pharmacology identified genistein and daidzein as key bioactive constituents targeting hub proteins TNF, AKT1, EGFR, SRC, and MMP9, which mediate pathological process in influenza. Molecular docking confirmed their strong binding affinities, particularly to lung-expressed AKT1 and SRC both of which are upstream activating kinases of the NF-\u03baB p65 signaling pathway. Guided by these computational predictions, genistein and daidzein were evaluated in A549 cells using LPS and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced influenza lung injury models. They significantly inhibited NF-\u03baB p65 nuclear translocation, suppressed transcription and secretion of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-8, PTGS2), upregulated antioxidant defense genes (NQO1, GCLM, SOD2), and reduced oxidative stress markers (ROS, MDA), thereby highlighting SSP\u2019s potential protective effects during influenza-induced pulmonary infection. Concurrently, SSP fermentation parameters were optimized (water-to-material ratio of 20:1 (v\/w), 30\u2009\u00b1\u20092\u00a0\u00b0C, open conditions), yielding nine SSP batches with high chromatographic similarity (&gt;\u20090.989) and genistein\/daidzein total contents exceeding Chinese Pharmacopoeia standards. Compared to commercial products, optimized SSP showed significantly higher indicator constituents\u2019 levels and superior quality consistency. This study establishes a robust, scalable framework for standardized SSP production, enhancing its clinical reliability and industrial applicability in influenza management.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-47737-7","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:25:27Z","timestamp":1775715927000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Network pharmacology-guided optimization of Semen Sojae Praeparatum fermentation for enhanced anti-influenza efficacy"],"prefix":"10.1038","volume":"16","author":[{"given":"Wenping","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-7895","authenticated-orcid":false,"given":"Wenlong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"47737_CR1","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1186\/s12879-025-10701-3","volume":"25","author":"H Xiang","year":"2025","unstructured":"Xiang, H. et al. 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