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

In the present study, carbon tetrachloride (CCl₄) was used to induce liver fibrosis in mice, and transforming growth factorβ1 (TGFβ1) was used to mimic liver fibrosis in vitro. 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.

中文翻译：

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辣椒素通过靶向Notch信号传导来抑制M1巨噬细胞的TNF-α分泌，从而减轻肝脏纤维化。

摘要

背景

辣椒素是具有多种治疗特性（包括抗肝纤维化）的辣椒提取物。然而，其潜在机制的缺乏限制了其广泛的临床应用。

方法

在本研究中，四氯化碳（CCl ₄）用于诱导小鼠肝纤维化，而转化生长因子β1（TGFβ1）用于体外模拟肝纤维化。进行流式细胞术以确定CD80的表达。通过ELISA检测炎性因子水平，并通过实时PCR和western blot检测基因表达。

结果

在这里，我们显示辣椒素通过介导巨噬细胞炎症反应来减轻肝纤维化的进展。辣椒素通过调节Notch信号传导导致炎性细胞因子TNF-α分泌减少，从而抑制巨噬细胞的M1极化，从而相应地减弱了肌成纤维细胞再生和肝星状细胞（HSCs）的纤维化形成。

结论

两者合计，辣椒素通过使Notch信号失活而减轻肝纤维化，并进一步抑制M1巨噬细胞的TNF-α分泌。靶向巨噬细胞中的TNF-α或Notch信号代表了对抗肝纤维化的有前途的策略。