Screening of anti-senescent traditional Chinese herbs and evaluation of their effects on suppression of senescence related molecule cofilin

• Main Authors: Yuan-Heng Tu, 杜元亨
• Other Authors: Yi-Jang Lee
• Format: Others
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/gf6kyx

碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 104 === Cellular senescence is an irreversible process that is caused by shortage of telomeres during DNA replication and cell division in mammalian cells. Morphological change is accompanied by the progression of senescence, and it is easily to be detected under microscope. Morphology change in senescent cells is associated with reorganization of actin filaments that can be controlled by various actin binding proteins (ABP). In previous studies, we have found that cofilin-1, a member of actin depolymerizing factor (ADF)/cofilin family protein is significantly up-regulated in senescent cells. Cofilin-1 is a 19kDa protein that can regulate cell shape and motility. Here we aimed to use the Chinese Medicine library provided by National Research Institute of Chinese Medicine, Ministry of Health and Welfare to screen the potent anti-senescence Chinese herbs and investigate whether they could suppress the expression of cofilin-1 in senescent cells. This library contains 338 drug extracts that were added to senescent human dermal fibroblasts (HDF), which were then examined using the senescence-associated β-galactosidase (SA-β-gal) staining assay. Three drug candidates (5200, 5428, 5438) were found to reduce the proportion of cellular senescence staining. We focused on 5428 with different solvent extracted materials, including ethanol extract, water extract, ethyl acetate extract and butanol extract to compare their ability on suppressing cell senescence and cofilin-1 level. The results showed that the ethanol extracted 5428 at concentration 100ng/µL exhibited most apparent effects on suppression of senescence and cofilin-1 level. It also reduces the G1 phase arrest of senescent HDF. Moreover, ethanol extracted 5428 could suppress the cofilin-1 expression even it was over-expressed in senescent cells. However, the MTT assay showed that the cell viability was reduced to 80%, suggesting that an optimal concentration of ethanol extracted 5428 remains to be addressed. Taken together, the ethanol extract of Traditional Chinese medicine 5428 may reduce cellular senescence by targeting on cofilin-1. It is interesting to further investigate the mechanisms of this extract on suppression of cofilin-1 and associated cellular senescence.