Baicalin improves the survival in endotoxic mice and inhibits the inflammatory responses in LPS-treated RAW 264.7 macrophages

Abstract

Introduction: Sepsis is a severe disease with a high morbidity and mortality. Baicalin, an active compound of Chinese medicine, Scutellaria baicalensis Georgi (Huang Qui), exhibits several beneficial effects. In this study, we examined whether administration of baicalin increases the survival in mice with endotoxemia and investigated its anti-inflammatory mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: The production of NOx, PGE2, and pro-inflammatory cytokines, the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the nuclear translocation of NF-κB in LPS-stimulated macrophages or endotoxic mice were determined. The model of severe endotoxic mice was established by injection of LPS (60 mg/kg, i.p.). Results: Baicalin significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6 in LPS-stimulated macrophages. Baicalin treatment also markedly suppressed LPS-induced iNOS and COX-2 expression at the transcriptional and translational levels, and the nuclear translocation of NF-κB in macrophages. Similarly, the serum concentrations of NOx, PGE2, and pro-inflammatory cytokines, and the lung myeloperoxidase activity were greatly reduced in baicalin-treated endotoxic mice. Notably, after LPS injection, the 3-day survival rate of mice treated with pre- or post-administration of baicalin (50 mg/kg, i.p.) remarkably increased to 100% and 90%, respectively compared with LPS-injected alone mice with a survival rate of 0%. Conclusion: Baicalin has a potent anti-inflammatory activity in LPS-stimulated macrophages and endotoxic mice. Moreover, treatment with baicalin dramatically increased the survival in the severe septic mice, suggesting that baicalin may be a potential agent for sepsis therapy.