Capsaicin attenuates liver fibrosis by targeting Notch signaling to inhibit TNF-α secretion from M1 macrophages
Jianping Sheng, Baohang Zhang, Yongfeng Chen, Fuxiang Yu
Abstract
BACKGROUND: Capsaicin is a chili pepper extract with multiple therapeutic properties including anti-liver fibrosis. However, the paucity of its underlying mechanisms limited its widely clinical application. METHODS: . Flow cytometry was conducted to determine the expression of CD80. The inflammatory factors level was examined by ELISA, and gene expression was detected by real-time PCR and western blot. RESULTS: Here, we show that capsaicin attenuates liver fibrosis progression by mediating macrophage inflammatory response. Capsaicin inhibited M1 polarization of macrophage by regulating Notch signaling leading to the reduced secretion of inflammatory cytokine TNF-α that correspondingly attenuates myofibroblasts regeneration and fibrosis formation of hepatocyte stellate cells (HSCs). CONCLUSION: Taken together, capsaicin alleviates liver fibrosis by inactivation of Notch signaling and further inhibiting TNF-α secretion from M1 macrophage. Targeting TNF-α or Notch signaling in macrophage represents a promising strategy to combat liver fibrosis.