ABSTRACT
Cycloastragenol (CAG) is an aglycone of astragaloside IV. It was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. The present study demonstrates that CAG stimulates telomerase activity and cell proliferation in human neonatal keratinocytes. In particular, CAG promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro. The distinct telomerase-activating property of CAG prompted evaluation of its potential application in the treatment of neurological disorders. Accordingly, CAG induced telomerase activity and cAMP response element binding (CREB) activation in PC12 cells and primary neurons. Blockade of CREB expression in neuronal cells by RNA interference reduced basal telomerase activity, and CAG was no longer efficacious in increasing telomerase activity. CAG treatment not only induced the expression of bcl2, a CREB-regulated gene, but also the expression of telomerase reverse transcriptase in primary cortical neurons. Interestingly, oral administration of CAG for 7 days attenuated depression-like behavior in experimental mice. In conclusion, CAG stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression. Furthermore, CAG may have a novel therapeutic role in depression.
Subject(s)
Depression/drug therapy , Neurons/drug effects , Neurons/metabolism , Sapogenins/administration & dosage , Telomerase/metabolism , Animals , Antidepressive Agents/administration & dosage , Cyclic AMP Response Element-Binding Protein/metabolism , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Mice , Nerve Growth Factor/metabolism , PC12 Cells , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Sapogenins/chemical synthesisABSTRACT
A new carotenoid glycoside, namely neo-rehmannioside (1), together with five known compounds, 6-O-seco-hydroxyaeginetoyl ajugol (2), oxyrehmaionoside B (3), ajugol (4), geniposidic acid (5) and geniposide (6) was isolated from the 95% ethanol extract of dry roots of Rehmannia glutinosa. The structure of the new compound (1) was determined based on MS, IR, 1-D and 2-D NMR spectral data.
