Curcuma phaeocaulis Valeton (Zingiberaceae) extract and compounds are efficacious to modulate prion propagation

초록

Aims: Evaluation of anti-prion efficacy of Curcuma phaeocaulis Valeton (Zingiberaceae) and identification of active compounds. Methods and Results: Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract is effec- tive in reducing 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 inhibited prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, com- pletely preventing the onset of prion disease in three of eight mice. PrPSc accumulation in the brain and spleen of mice was statistically significantly reduced. Furthermore, 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. Next, We endea- voured to identify the chemical constituents of CpV extracts and discover potential anti-prion active com- pounds. Utilizing centrifugal partition chromatography (CPC), major constituents were isolated from the n-hexane (HX) fraction of the extract in a single step. Spectroscopic analysis confirmed the presence of curcumenone, curcu- menol, and furanodienone. Subsequent efficacy testing in a cell culture model of prion disease identified curcumenol and furanodienone as active compounds. This study sug- gests the potential of natural products in finding effective treatments against prion diseases. Conclusions: CpV extract has an anti-prion effect that inhibits the aggregation and propagation of prions. Two anti-prion active compounds (curcumenol and furanodienone) were identified in the CpV extract.