Protective role of gambogic acid in experimental pulmonary fibrosis in vitro and in vivo

详细信息    查看全文

• 作者：Yubei Qu¹ ; Guanghua Zhang¹ ; Yunxia Ji ; Haibo Zhua ; Changjun Lv ^{Lucky_lcj@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Wanglin Jiang ; ^{jwl518@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Gambogic acid ; Pulmonary fibrosis ; TGF-β1/Smad3 ; Vasohibin-1 ; Vasohibin-2
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：23
• 期：4
• 页码：350-358
• 全文大小：2435 K

文摘

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. The treatment options for IPF are very limited. Gambogic acid (GA) has anticancer effect and anti-proliferative activity which is extracted from a dried yellow resin of the Garcinia hanburyi Hook.f. [Clusiaceae (Guttiferae)] in Southeast Asia. However, the anti-fibrotic activities of GA have not been previously investigated.

Methods

In this study, the effects of GA on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells and endothelial–mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMECs), on the proliferation of human lung fibroblasts (HLF-1) were investigated in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo.

Results

In TGF-β1 stimulated A549 cells, treatment with GA resulted in a reduction of EMT with a decrease in vimentin and p-Smad3 and an increase in E-cadherin instead. In TGF-β1 stimulated HPMECs, treatment with GA resulted in a reduction of EndoMT with a decrease in vimentin, and an increase in VE-cadherin instead. In the hypoxic HPMECs, treatment with GA reduced Vasohibin-2 (VASH-2), whereas increased VASH-1. In TGF-β1 stimulated HLF-1, treatment with GA reduced HLF-1 proliferation with a decrease in platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF-2) expressions. In vivo, treatment with GA for 2 weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower VASH-2. Instead, it was observed a higher VASH-1 expression at early stage of fibrosis at 1 mg/kg, with reductions of the pathological score, collagen deposition, α-SMA, PDGF and FGF-2 expressions at fibrotic stage at 0.5 mg/kg and 1 mg/kg.

Conclusion

In summary, GA reversed EMT and EndoMT, as well as HLF-1 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating VASH-2/VASH-1 and suppressing the TGF-β1/Smad3 pathway.