Pan Ruiyan, Zhang Yadan, Zang Baoxia, Tan Li, Jin Ming
Department of Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang district, Beijing, 100029, China.
J Pharm Pharmacol. 2016 Oct;68(10):1320-30. doi: 10.1111/jphp.12596. Epub 2016 Jul 26.
Hydroxysafflor yellow A (HSYA) is one of the chemical component isolated from Chinese medicine Carthamus tinctorius L. Our preliminary study confirmed that HSYA attenuated bleomycin-induced pulmonary fibrosis in mice. In this study, we evaluated the effect of HSYA on TGF-β1-induced activation of human fetal lung fibroblasts (MRC-5) and explored the underlying mechanisms of its activity.
MRC-5 cells activated by TGF-β1 were incubated with HSYA and/or the TGF-β type I receptor inhibitor, SB431542. TGF-β1-induced cell proliferation, α-smooth muscle actin, collagen I alpha 1 and fibronectin expression, Smad, mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase/Akt signalling pathway activation were observed.
Hydroxysafflor yellow A significantly inhibited TGF-β1-induced cell proliferation and the expression, both mRNA and protein, of α-smooth muscle actin, collagen I alpha 1 and fibronectin. HSYA also suppressed TGF-β1 activation of Smad signal transduction via inhibition of Smad2 and Smad3 phosphorylation, their nuclear translocation and the binding activity of Smad3 to type I collagen promoter in MRC-5 cells. In addition, HSYA inhibited TGF-β1-induced phosphorylation of extracellular signal-regulated kinase (ERK). The inhibitory effects of HSYA were similar to SB431542.
These findings suggest that HSYA inhibits TGF-β1-induced activation of MRC-5 cells associated with TGF-β1/Smad and ERK/MAPK signalling pathways.
羟基红花黄色素A（HSYA）是从中药红花中分离出的化学成分之一。我们的初步研究证实，HSYA可减轻博来霉素诱导的小鼠肺纤维化。在本研究中，我们评估了HSYA对转化生长因子-β1（TGF-β1）诱导的人胚肺成纤维细胞（MRC-5）激活的影响，并探讨了其作用的潜在机制。
将经TGF-β1激活的MRC-5细胞与HSYA和/或TGF-βⅠ型受体抑制剂SB431542一起孵育。观察TGF-β1诱导的细胞增殖、α-平滑肌肌动蛋白、Ⅰ型胶原α1和纤连蛋白的表达，以及Smad、丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）信号通路的激活情况。
羟基红花黄色素A显著抑制TGF-β1诱导的细胞增殖以及α-平滑肌肌动蛋白、Ⅰ型胶原α1和纤连蛋白的mRNA和蛋白表达。HSYA还通过抑制Smad2和Smad3磷酸化、它们的核转位以及Smad3与MRC-5细胞中Ⅰ型胶原启动子的结合活性，抑制TGF-β1激活的Smad信号转导。此外，HSYA抑制TGF-β1诱导的细胞外信号调节激酶（ERK）磷酸化。HSYA的抑制作用与SB431542相似。
这些发现表明，HSYA抑制TGF-β1诱导的与TGF-β1/Smad和ERK/MAPK信号通路相关的MRC-5细胞激活。
