Panax notoginseng saponins inhibit areca nut extract-induced oral submucous fibrosis in vitro
Panax notoginseng saponins inhibit areca nut extract-induced oral submucous fibrosis in vitro
复制标题
三七总皂苷体外抑制槟榔提取物诱导的口腔粘膜下纤维化
DOI：
10.1111/jop.12158
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发表时间：
2014-07-01
影响因子：
3.3
通讯作者：
Li, Kang-Sheng
中科院分区：
文献类型：
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作者：
Dai, Jian-Ping;Chen, Xiao-Xuan;Li, Kang-Sheng
背景：口腔粘膜下纤维性变（Oral submucous fibrosis，OSF）是一种与咀嚼槟榔的习惯密切相关的癌前病变和纤维化疾病。三七H. Chen是一种常用的抗纤维化和抗肿瘤药物。为治疗槟榔所致的口腔黏膜下炎，我们研制了以三七总皂苷（PNS）为主药的咀嚼片。本研究旨在探讨三七总皂苷对槟榔诱导的OSF的抗纤维化作用及其机制。通过人前胶原基因启动子荧光素酶报告质粒、羟脯氨酸测定、明胶酶谱、qRT-PCR、ELISA和Western blot等方法，研究三七总皂苷对槟榔提取物（ANE）诱导的细胞生长、胶原积累、前胶原基因转录、MMP-2/-9活性、结果：三七总皂苷能抑制ANE诱导的口腔黏膜成纤维细胞的异常生长和胶原沉积，并呈浓度依赖性。PNS（25 μ g/ml）可显著抑制ANE诱导的Col 1A 1和Col 3A 1的表达，增强ANE诱导的MMP-2/-9活性的降低，抑制ANE诱导的TIMP-1/-2表达的增加，减少ANE诱导的CTGF、TGF β 1、IL-6和TNF α的转录和释放。PNS（25 μ g/ml）还显著抑制ANE诱导的口腔粘膜成纤维细胞中AKT和ERK/JNK/p38 MAPK通路的激活以及ANE诱导的HaCaT细胞中TGF β/smad通路的激活。三七总皂苷具有良好的抗OSF活性，其机制可能与抑制ANE诱导的PI 3 K/AKT、ERK/JNK/p38 MAPK、和TGF β/smad通路。
BACKGROUND: Oral submucous fibrosis (OSF) is a premalignant and fibrosing disease, which is closely associated with the habit of chewing areca nut. Panax notoginseng Buck F. H. Chen is an often used antifibrotic and antitumor agent. To treat areca nut-induced OSF, we have developed a chewable tablet, in which one of the major medicines is total Panax notoginseng saponins (PNS). In this study, we have investigated the antifibrotic effect and mechanism of PNS on areca nut-induced OSF in vitro.METHODS: Through human procollagen gene promoter luciferase reporter plasmid, hydroxyproline assay, gelatin zymography, qRT-PCR, ELISA, and Western blot, the influences of PNS on areca nut extract (ANE)-induced cell growth, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion, and the activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGF beta/Smads pathways were detected.RESULTS: Panax notoginseng saponins could inhibit the ANE-induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration-dependent manner. PNS (25 mu g/ml) could significantly inhibit the ANE-induced expression of Col1A1 and Col3A1, augment the ANE-induced decrease of MMP-2/-9 activity, inhibit the ANE-induced increase of TIMP-1/-2 expression, and decrease the ANE-induced transcription and release of CTGF, TGF beta 1, IL-6, and TNF alpha. PNS (25 mu g/ml) also significantly inhibited the ANE-induced activation of AKT and ERK/JNK/p38 MAPK pathways in oral mucosal fibroblasts and the ANE-induced activation of TGF beta/smad pathway in HaCaT cells.CONCLUSION: Panax notoginseng saponins possess excellent anti-OSF activity, and its mechanism may be related to its ability to inhibit the ANE-induced activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGF beta/smad pathways.