Pretreatment with Salvia miltiorrhiza Polysaccharides Protects from Lipopolysaccharides/d-Galactosamine-Induced Liver Injury in Mice Through Inhibiting TLR4/MyD88 Signaling Pathway.

The study was conducted to investigate the protective effects of Salvia miltiorrhiza polysaccharides (SMPs) on lipopolysaccharides (LPS)/d-galactosamine (d-GalN)-induced liver injury in mice and its mechanism. Seventy-two mice were allocated to 6 groups of 12 each, that is, the untreated control group, the liver injury model group, the Bifendate group (Bifendate 200 mg/kg/day), and 3 SMP-treated groups at low (250 mg/kg/day), medium (500 mg/kg/day), and high doses (750 mg/kg/day). After 12 days oral treatment, liver injury was induced with LPS/d-GalN, and 1 h later the mice were sacrificed for a series of analyses. The results showed that SMPs significantly alleviated pathological changes in the hepatic tissue. Compared with the untreated control group, the messenger RNA (mRNA) levels of lipopolysaccharide-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation factor 2 (MD-2), toll-like receptor 4 (TLR4), and myeloid differentiation primary response protein 88 (MyD88) detected by quantitative real-time polymerase chain reaction (qRT-PCR), the protein levels of TLR4, MyD88, phosphorylated inhibitor of nuclear factor kappa-B kinase alpha/beta (P-IKK-α/β), phosphorylated inhibitor of NF-κB alpha (P-IκB-α) and phosphorylated P65 (P-P65) detected by Western blot, the levels of C-X-C motif chemokine 10 (CXCL-10) and Intercellular Adhesion Molecule 1 (ICAM-1) detected by immunohistochemistry, and the concentrations of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) detected by enzyme-linked immunosorbent assay of liver injury model group were increased significantly (P < 0.01). Compared with liver injury model group, the mRNA levels of LBP, CD14, MD-2, TLR4, and MyD88; protein levels of TLR4, MyD88, P-IKK-α/β, P-IκB-α, and P-P65; levels of CXCL-10 and ICAM-1; and the concentrations of TNF-α and IL-1β of SMP groups and Bifendate group were decreased significantly (P < 0.01 or P < 0.05). In conclusion, SMPs can effectively inhibit TLR4/MyD88 inflammatory signaling pathway of LPS/d-GalN-induced liver injury in mice, and it may be part of the mechanism by which SMPs relieve excessive inflammation in the liver of mice.