Anti-inflammatory Activity And Regulation On Inflammatiory Signal Transduction Pathway Of Salidroside

Salidroside is a phenylpropanoid glycoside extracted from Rhodiola rosea and regarded as the most important bioactive component. It has been reported to have various pharmacological properties including anti-aging, anticancer, hepatoprotective, antivirus and antioxidative effects. In this paper, we study the anti-inflammatory activity of salidroside deeply. We built in vitro inflammatory model by LPS-stimulated murine RAW 264.7 macrophages, and further explored anti- inflammatory molecular mechanism of salidrosie by cellular second messenger and inflammatory signal transduction pathway. Meanwhile, we studied the effects of salidroside on LPS-induced murine ALI and endotoxic shock.LPS-mediated activation of macrophages leads to the production of various cytokines such as tumour necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6) and inflammation mediators such as nitric oxide (NO) and prostaglandin E2 (PGE₂). The production of these cytokines may result in the systemic inflammatory response syndrome (SIRS), severe tissue damage, and septic shock. So lipopolyssacharide (LPS)-activated macrophages have typically been used to evaluate the anti-inflammatory effects of various materials. First, we investigated the effect of different concentrations of salidroside on cytokine TNF-α, IL-1β, IL-6. The result showed that salidroside inhibited TNF-α, IL-6 and IL-1βsecretion level in a dose-dependent manner, consistent with cytokine mRNA expression. Salidroside also inhibited NO and PGE₂ synthesis in LPS-stimulated murine RAW 264.7 macrophages by inhibiting iNOS and COX-2 protein expression, cytosolic free Ca²⁺ ([Ca²⁺]_i), and increasing cAMP level.NF-κB and MAPKs are known as important targets for anti-inflammatory molecular mechanism. In order to study anti-infalmmatory molecular mechanism, we further investigated the effect of salidroside on NF-κB and MAPKs signal transduction pathways in LPS-stimulated murine RAW264.7 macrophages. The result showed that salidroside inhibited NF-κB activity, ERK1/2 and p38 protein phosphorylation in a dose-dependent manner. It suggested that salidroside inhibited cytokine TNF-α, IL-1β, IL-6, NO and PGE₂ secretion by regulating both NF-κB and ERK and p38 MAPKs pathways.We further studied in vivo ant-inflammatory of salidroside. In this study, we established a mouse model of LPS-induced inflammatory lung injury and investigated the effect of salidroside (120 mg/kg) on acute lung injury eight hours after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, histological change. We found that the preadministration of salidroside significantly decreases the W/D ratio of lungs, protein concentrations and the number of total cells, neutrophils, macrophages and leukomonocytes, and histologic analysis indicates that salidroside significantly attenuates tissue injury. Furthermore, salidroside significantly increases LPS-induced lung MPO activity, consistent with its effects on neutrophil infiltration. In addition, salidroside also inhibits the production of TNF-α, L-6, and IL-1β. The results showed that salidroside had a protective effect on LPS-induced inflammatory lung injury in mice.We investigated the effect of different concentrations of salidroside on preventive and therapeutic effect in LPS-induced endotoxic shock mice, and the effect on cytokine TNF-α, IL-1β, IL-6 production in murine serum. The result showed that salidroside significantly improved murine survival rate and decreased TNF-α, IL-1βand IL-6 level in serum. It suggested that salidroside improved murine survival rate through regulating the level of cytokines.