Eiden Martin, Leidel Fabienne, Strohmeier Barbara, Fast Christine, Groschup Martin H
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health Greifswald, Germany.
Front Psychiatry. 2012 Feb 17;3:9. doi: 10.3389/fpsyt.2012.00009. eCollection 2012.
Transmissible spongiform encephalopathies (TSE) are characterized by the misfolding of the host encoded prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)) which leads to the accumulation of β-sheet-rich fibrils and subsequent loss of neurons and synaptic functions. Although many compounds have been identified which inhibit accumulation or dissolve fibrils and aggregates in vitro there is no therapeutic treatment to stop these progressive neurodegenerative diseases. Here we describe the effects of the traditional medicinal herb Scutellaria lateriflora (S. lateriflora) and its natural compounds, the flavonoids baicalein and baicalin, on the development of prion disease using in vitro and in vivo models. S. lateriflora extract as well as both constituents reduced the PrP(res) accumulation in scrapie-infected cell cultures and cell-free conversion assays and lead to the destabilization of pre-existing PrP(Sc) fibrils. Moreover, tea prepared from S. lateriflora, prolonged significantly the incubation time of scrapie-infected mice upon oral treatment. Therefore S. lateriflora extracts as well as the individual compounds can be considered as promising candidates for the development of new therapeutic drugs against TSEs and other neurodegenerative diseases like Alzheimer's and Parkinson's disease.
传染性海绵状脑病（TSE）的特征在于宿主编码的朊病毒蛋白（PrP(C)）错误折叠为致病异构体（PrP(Sc)），这导致富含β-折叠的纤维积累以及随后神经元和突触功能丧失。尽管已经鉴定出许多在体外抑制积累或溶解纤维和聚集体的化合物，但尚无治疗方法来阻止这些进行性神经退行性疾病。在此，我们使用体外和体内模型描述了传统草药半枝莲（S. lateriflora）及其天然化合物黄酮类化合物黄芩素和黄芩苷对朊病毒病发展的影响。半枝莲提取物以及这两种成分均减少了瘙痒病感染细胞培养物和无细胞转化试验中PrP(res)的积累，并导致预先存在的PrP(Sc)纤维不稳定。此外，用半枝莲制备的茶在口服治疗后显著延长了瘙痒病感染小鼠的潜伏期。因此，半枝莲提取物以及单个化合物可被视为开发针对TSE以及其他神经退行性疾病如阿尔茨海默病和帕金森病的新治疗药物的有前景的候选物。
