• J. Oral Pathol. Med. · Jul 2014

    Panax notoginseng saponins inhibit areca nut extract-induced oral submucous fibrosis in vitro.

    • Jian-Ping Dai, Xiao-Xuan Chen, Dan-Xia Zhu, Qian-Ying Wan, Cheng Chen, Ge-Fei Wang, Wei-Zhong Li, and Kang-Sheng Li.
    • Department of Microbiology and Immunology, Shantou University Medical College, Shantou, Guangdong, China.
    • J. Oral Pathol. Med. 2014 Jul 1; 43 (6): 464-70.

    BackgroundOral 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.MethodsThrough 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 TGFβ/Smads pathways were detected.ResultsPanax notoginseng saponins could inhibit the ANE-induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration-dependent manner. PNS (25 μg/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, TGFβ1, IL-6, and TNFα. PNS (25 μg/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 TGFβ/smad pathway in HaCaT cells.ConclusionPanax 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 TGFβ/smad pathways.© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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