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Diverse stimuli can disrupt spleen homeostasis, resulting in spleen injury and immune dysfunction. This study employed a porcine model to assess the therapeutic potential of salvianolic acid B (SAB) against lipopolysaccharide (LPS)-induced splenic injury. Methods: Seventy-two male weanling piglets were randomly assigned to one of four groups: CON-SS, SAB-SS, CON-LPS, and SAB-LPS. The CON-SS and CON-LPS groups received a basal diet, while SAB-SS and SAB-LPS groups received a SAB-supplemented diet. After 14 d, the CON-SS and SAB-SS groups received an intraperitoneal injection of sterile saline, whereas the CON-LPS and SAB-LPS groups were injected with LPS. Blood and spleen tissues were harvested 6 h post-injection for biochemical analysis. Results: LPS induced systemic immune disorders in piglets, as evidenced by increased immune organ indices and decreased white blood cell, lymphocyte, and basophil counts in blood (p &lt; 0.05). LPS also caused histoarchitectural disruption, cell apoptosis, oxidative stress, and inflammation in the spleen (p &lt; 0.05). Conversely, SAB improved splenic histopathology and reduced splenic apoptosis and pro-inflammatory mediators in piglets (p &lt; 0.05). SAB significantly mitigated peroxidation accumulation by facilitating the nuclear translocation of nuclear factor erythroid 2-related factor 2 and strengthening the antioxidant system, and inhibited nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activation (p &lt; 0.05). Mechanistically, SAB attenuated LPS-induced splenic oxidative stress and NLRP3 inflammasome activation by restoring mitochondrial structure and function (p &lt; 0.05). Conclusions: This research unveils that SAB alleviates LPS-induced spleen disorder by reinforcing antioxidant system and suppressing NLRP3 inflammasome, highlighting SAB\u2019s potential as a prospective therapeutic agent for spleen disorders.<\/jats:p>","DOI":"10.3390\/antiox14070883","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T12:09:53Z","timestamp":1752840593000},"page":"883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Salvianolic Acid B Alleviates LPS-Induced Spleen Injury by Remodeling Redox Status and Suppressing NLRP3 Inflammasome"],"prefix":"10.3390","volume":"14","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"National Key Laboratory for the Development and Utilization of Forest Food Resources, Nanjing Forestry University, Nanjing 210037, China"},{"name":"Key Laboratory of Veterinary Biological Products Engineering, Ministry of Agriculture and Rural Affairs, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Dou","sequence":"additional","affiliation":[{"name":"Shandong Provincial Forestry Protection and Development Service Center, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Forestry Protection and Development Service Center, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Key Laboratory for the Development and Utilization of Forest Food Resources, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory for the Development and Utilization of Forest Food Resources, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianjuan","family":"Qiao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Forestry Protection and Development Service Center, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Forestry Protection and Development Service Center, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science & Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhuan","family":"Lai","sequence":"additional","affiliation":[{"name":"National Key Laboratory for the Development and Utilization of Forest Food Resources, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory for the Development and Utilization of Forest Food Resources, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yong","sequence":"additional","affiliation":[{"name":"National Key Laboratory for the Development and Utilization of Forest Food Resources, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. 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