Salvianolic Acid B Alleviates LPS-Induced Spleen Injury by Remodeling Redox Status and Suppressing NLRP3 Inflammasome.

Abstract

<b>Background</b>: The spleen is the primary reservoir of immune cells in mammals. 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> < 0.05). LPS also caused histoarchitectural disruption, cell apoptosis, oxidative stress, and inflammation in the spleen (<i>p</i> < 0.05). Conversely, SAB improved splenic histopathology and reduced splenic apoptosis and pro-inflammatory mediators in piglets (<i>p</i> < 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 (<i>p</i> < 0.05). Mechanistically, SAB attenuated LPS-induced splenic oxidative stress and NLRP3 inflammasome activation by restoring mitochondrial structure and function (<i>p</i> < 0.05). <b>Conclusions</b>: This research unveils that SAB alleviates LPS-induced spleen disorder by reinforcing antioxidant system and suppressing NLRP3 inflammasome, highlighting SAB's potential as a prospective therapeutic agent for spleen disorders.