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Sesamoside Alleviates Inflammatory Response in Septic Shock-Associated Acute Liver Injury by Modulating the
Xinjie Zhao1, Xiaohua Hao1, Jialu Yuan1,2
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.
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.
