Sesamoside Alleviates Inflammatory Response in Septic Shock-Associated Acute Liver Injury by Modulating the NF-κB/MAPK Signaling Pathway.

OBJECTIVES: Acute liver injury, a lethal septic shock complication with scarce treatments, lacks research on Sesamoside's liver-protective function. We explored its protective mechanisms against lipopolysaccharide (LPS)-induced liver injury via the nuclear factor kappa B/mitogen-activated protein kinases (NF-κB/MAPK) pathway. METHODS: Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and NF-κB/MAPK pathway were screened via bioinformatic analysis, and an LPS-induced mouse model was established for in vivo verification. Quantitative real-time polymerase chain reaction (qPCR) detected cytokines and vasoactive factors; Western blot measured proteins; Hematoxylin and eosin (H&E) staining and Immunohistochemistry (IHC) assessed liver pathology. RESULTS: 1-, 5-, and 10 mg/kg Sesamoside suppressed LPS- triggered excess TNF-α (∼97%, p < 0.0001), IL-6 (∼95%, p < 0.0001), IL-1β (∼91%, p = 0.0011) and nitric oxide (NO) (∼96%, p < 0.0001). It reduced NOD-like receptor family pyrin domain-containing 3 (NLRP3) by ∼25% (p < 0.0001), and decreased nuclear factor-kappa B p65 subunit (P65), phosphorylated extracellular signal-regulated kinase/total extracellular signal-regulated kinase (p-ERK/ERK), phosphorylated c-Jun N-terminal kinase/total c-Jun N-terminal kinase (p-JNK/JNK) by 61% (p < 0.0001), 25% (p = 0.0066) and 49% (p < 0.0001) respectively. Liver injury and inflammatory infiltration were markedly attenuated. CONCLUSION: Sesamoside alleviates septic shock-related acute liver injury by inhibiting NF-κB/MAPK signaling and excessive inflammation, providing a promising natural compound for targeted therapy development.