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The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models
Authors:Sungeun Lee  Hakmin Lee  Jaehyeon Kim  Ji Hoon Kim  Eun Mei Gao  Yoonjeong Lee  Miryeong Yoo  Trang H. T. Trinh  Jieun Kim  Chul Young Kim  Chongsuk Ryou
Affiliation:Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Science & Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Gyeonggi-do, Republic of Korea
Abstract:
Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.
Keywords:prions   inhibition   Curcuma phaeocaulis Valeton   natural products
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