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

[oral submucous fibrosis]

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 .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 PI 3 K /AKT , ERK /JNK /p 38 MAPK , and TGF β /Smads pathways were detected .Panax 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 Col 1 A 1 and Col 3 A 1 , 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 , TGFβ 1 , IL -6 , and TNF α . PNS (25 μg /ml ) also significantly inhibited the ANE-induced activation of AKT and ERK /JNK /p 38 MAPK pathways in oral mucosal fibroblasts and the ANE-induced activation of TGF β /smad pathway in HaCaT cells .P anax notoginseng saponins possess excellent anti-OSF activity , and its mechanism may be related to its ability to inhibit the ANE-induced activation of PI 3 K /AKT , ERK /JNK /p 38 MAPK , and TGFβ /smad pathways .