Salidroside alleviates LPS-induced liver injury and inflammation through SIRT۱- NF-κB pathway and NLRP۳ inflammasome

Objective(s): Salidroside (SAL), an active ingredient purified from the medicinal plant Rhodiola rosea, has anti-inflammatory, anti-oxidant, anticancer, and neuroprotective properties. The study aims to examine SAL’s protective role in liver damage brought on by lipopolysaccharide (LPS). Materials and Methods: Six to eight-week-old male C۵۷BL/۶ wild-type mice were intraperitoneally treated with ۱۰ mg/kg LPS for ۲۴ hr and ۵۰ mg/kg SAL two hours before  LPS administration. Mice were categorized into control, LPS, and LPS + SAL groups. To evaluate liver injury, biochemical and TUNNEL staining test studies were performed. The Elisa assay analyzed interleukin- ۱β (IL-۱β), tumor necrosis factor-alpha (TNF-α), and interleukin-۶ (IL-۶) pro-inflammatory cytokine expression levels. RT-qPCR and western blotting measured mRNA and protein expression of SIRT۱, NF-кB, NLRP۳, cleaved caspase-۱, and GSDMD, respectively.Results: Analysis of the serum alanine/aspartate aminotransferases (ALT/AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) revealed that SAL protected against hepatotoxicity induced by LPS. The pathological evaluation of the liver supported the protection provided by SAL. SAL treatment reversed IL-۱β, TNF-α, and IL-۶ pro-inflammatory cytokines after being induced by LPS (all, P<۰.۰۰۱). The western blotting examination results demonstrated that SAL increased the levels of Sirtuin ۱ (SIRT۱) expression but markedly reduced the phosphorylation of Nuclear Factor Kappa B (NF-B) and the expressions of NLRP۳, cleaved caspase-۱, and gasdermin D (GSDMD) induced by LPS (all, P<۰.۰۰۱).Conclusion: Our results speculated that by inhibiting the SIRT۱- NF-κB pathway and NLRP۳ inflammasome, SAL defends against LPS-induced liver injury and inflammation.

کلیدواژه ها:

Anti-inflammation ، Lipopolysaccharide ، Liver injury ، Nuclear factor Kappa B ، Salidroside