Effects of Oleanane-Type Triterpene Saponins from the Leaves of Eleutherococcus senticosus in an Axonal Outgrowth Assay.

An aqueous extract of Eleutherococcus senticosus leaves exerted a beneficial effect in restoring the neurite outgrowth from Aβ25-35-induced degeneration using an axonal density assay. Subsequent bioassay-guided fractionation afforded seven new oleanane-type triterpene saponins, ezoukoginosides A-G (1-7), along with nine known analogues. The structures of 1-7 were elucidated through chemical and spectroscopic approaches, and their effects on restoring the neurite outgrowth from Aβ25-35-induced degeneration were investigated. The results revealed that hydrophilic oleanane-type saponins substituted with a free carboxylic acid, hydroxy, or formyl group in the aglycone, especially when the oxidation occurred at C-29, not only restrained Aβ25-35-induced degeneration but also restored axonal outgrowth significantly. Compounds 2 (-COOH at C-29) and 3 (-CH2OH at C-29) showed the most potent bioactivity among the isolates.