Effects of edpetiline from Fritillaria on inflammation and oxidative stress induced by LPS stimulation in RAW264.7 macrophages

Abstract The dry bulbs of Fritillaria cirrhosa species can help resolve phlegm, soothe cough, clear heat, and moisten the lung, and the main active components responsible for these effect are its alkaloids. However, it is unclear whether or how edpetiline in Fritillaria can inhibit the excessive inflammatory response and oxidative stress. In this research, we aimed to examine this aspect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages as an inflammatory model. The quantitative real-time polymerase chain reaction and western blot analysis results showed that edpetiline significantly inhibited the content and mRNA expression levels of proinflammatory cytokines (TNF-α and IL-6) in LPS-induced RAW264.7 cells, significantly increased the mRNA expression of IL-4 (anti-inflammatory cytokine), and markedly downregulated the inflammatory mediators inductible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein expression levels. The oxidative stress induced by LPS was also inhibited by edpetiline, as the level of intracellular reactive oxygen species decreased notably. Edpetiline may exert anti-inflammatory and antioxidant effects through inhibiting the phosphorylation of IκB and the nuclear transcription of nuclear transcription factor-κB p65 and decreasing the phosphorylation of p38 and ERK in the mitogen-activated protein kinase signaling pathway, without activating the JNK/mitogen-activated protein kinase signaling pathway. These findings suggest that edpetiline may be a potential therapeutic agent for the prevention or treatment of inflammation- and oxidative stress-related pathophysiological processes and diseases.