Screening for natural inhibitors in Chinese medicinal plants against Glycogen synthase kinase 3β (GSK-3β)

Background: The aim of this study is screening Chinese medicinal plants for inhibitors of Glycogen synthase kinase-3 (GSK-3). GSK-3 is a proline/serine protein kinase ubiquitously expressed and involved in many cellular signalling pathways. GSK-3 has emerged as one of the most attractive therapeutic targets for the development of selective inhibitors as promising new drugs for numerous pathologies, including neurodegenerative diseases and type II diabetes. Thus, the use of GSK-3 inhibitors is one of the most promising therapeutic strategies for the future treatment of these potentially life threatening diseases. Materials and Methods: In the aim of discovery of potential inhibitors, 42 traditional Chinese medicinal plants were screened against GSK-3β which were selected based on their folklore use. The selected plant materials were extracted with ethanol and water. In vitro assay was carried out to evaluate the inhibition of human GSK-3~. The Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was conducted with immortalized Hepatocyte cell line (Fa2N4) to evaluate the cytotoxicity of the plant material. Results: Many new ethanol and aqueous extracts showed significant inhibitory activity against GSK-3~ with moderate or no cytotoxicity. Water extracts of Prunella vulgaris, Rabdosia rubescens and Sarcandra glabre have exhibited highest inhibition against GSK-3β. This in turn was supported by the fact that a good correlation exists between GSK-3β inhibitory activity and antioxidant content of the extracts. Conclusion: Considering the potent activity of P. vulgaris, R. rubescens and S. glabre, further isolation and characterization of individual bioactive compounds is recommended for the discovery of potent natural inhibitors of GSK-3β.