Journal of Ethnopharmacology 127 (2010) 419–423 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Panaxatriol saponins extracted from Panax notoginseng induces thioredoxin-1 and prevents 1-methyl-4-phenylpyridinium ion-induced neurotoxicity Fu-Cheng Luo a , Sheng-Dong Wang a , Kui Li a , Hajime Nakamura b , Junji Yodoi c , Jie Bai a,∗ a College of Life Science and Technology, Kunming University of Science and Technology, No. 296 Bailong Temple, Kunming 650224, China b Department of Preventive Medicine, The Tazuke Kofukai Medical Research Institute Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan c Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan article info Article history: Received 3 May 2009 Received in revised form 28 September 2009 Accepted 16 October 2009 Available online 24 October 2009 Keywords: Panaxatriol saponins Panax notoginseng Thioredoxin-1 Parkinson’s disease abstract Aim of the study: Thioredoxin-1 has various biologic activities, including the control of redox balance and the inhibition of apoptosis. The current study was designed to examine the effects of panaxatriol saponins (PTS) extracted from Panax notoginseng on thioredoxin-1 expression and 1-methyl-4-phenylpyridinium ion-induced injury. Materials and methods: Using PC12 cells and Kunming mice, we test thioredoxin-1 expression after PTS treatment by Western blot. The protective effect of PTS against 1-methyl-4-phenylpyridinium ion- induced injury was assessed by MTT assay and LDH release assay. Results: PTS induced thioredoxin-1 expression in vitro and in vivo, and attenuated 1-methyl-4- phenylpyridinium ion-induced cell death of PC12 cells. Conclusions: PTS is a new inducer of thioredoxin-1 and has a possible potential as a therapeutic agent for neurodegenerative diseases including Parkinson’s disease. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Thioredoxin-1 (TRX-1) is a 12-kDa multifunctional protein with a redox-active disulfide/dithiol within its active site sequence, -Cys- Gly-Pro-Cys-. TRX-1 shows the promotive effect on cell growth and the inhibitory effect on apoptosis. It has been reported that TRX-1 acts as a neurotrophic co-factor which augments the effect of nerve growth factor on neuronal differentiation and regeneration (Bai et al., 2003). Thioredoxin transgenic mice display elongated life span and resistance against ischemic injury, diabetes and toxicity caused by environmental stressors (Hamada et al., 2007; Mitsui et al., 2002; Takagi et al., 1999; Watson et al., 2004). A body of evidence indi- cates that TRX-1 provides cytoprotection against oxidative stress and modulation of TRX-1 expression may represent a novel target for therapeutic intervention. A view that a non-cytotoxic pharma- cological inducer of TRX-1 is beneficial for neurogeneration and protection against oxidative stress-associated neural diseases has been presented (Masutani et al., 2004). Recently, several studies have used TRX-1 inducers, such as neurotropin, geranylgerany- lacetone and sulforaphane, for therapeutic purposes. Neurotropin, an analgesic drug, increases TRX-1 expression and ameliorates cigarette smoke-induced lung injury in mice (Hoshino et al., 2007). Geranylgeranylacetone and sulforaphane have the potential to ∗ Corresponding author. Tel.: +86 13354980126; fax: +86 8713801191. E-mail address: jiebai662001@yahoo.com.cn (J. Bai). induce TRX-1 and attenuate retinal light damage in mice (Tanito et al., 2005a,b). Panax notoginseng (Sanqi or Tianqi in Chinese) is the root of Panax notoginseng (Burk.) F.H. Chen. It belongs to the family Arali- aceae. Panax notoginseng has been a key component in Chinese herbal medicine for more than 600 years. It is used for treatment of cardio- and cerebro-vascular diseases, different body pains and bleeding (Ng, 2006). Panax notoginseng treatment can enhance the expression of Nestin and BDNF (Wang et al., 2007). The neuronal plasticity and functional recovery following focal cerebral ischemia are promoted after Panax notoginseng treatment (Guo et al., 2003). Panax notoginseng saponins (PNS) are considered as its main bioac- tive principles. Various products of PNS are commercially available and widely applied to the clinical medicine in China. PNS are com- posed of panaxadiol saponins and panaxatriol saponins (PTS). In the present study we found that TRX-1 expression was induced by PTS. Furthermore, we demonstrated that PTS attenuated 1-methyl- 4-phenylpyridinium ion (MPP + )-induced cell death of PC12 cells. 2. Materials and methods 2.1. Materials Panaxatriol saponins (PTS) extracted from Panax notogin- seng was obtained from Kunming Pharmaceutical Corporation (Kunming, China). Ginsenoside Rg1, R1 and Re are the main compo- nents of PTS (about 80%), and the content of ginsenoside Rg1 is up 0378-8741/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2009.10.023