Polygalae Radix (PR) is traditionally used for dementia. Extracts of PR reportedly improved memory in elderly human and dementia mouse models. We previously found that the water extract of PR induced axonal growth in amyloid β-treated cultured neurons, and increased M2 microglia that showed anti-inflammatory and neuroprotective effects. These effects might contribute to memory recovery in the mouse models. In this study, we aimed to identify active constituents in the PR extract and analyze mechanisms of the constituents.
Thirty minutes after oral administration of the PR extract to normal mice, sibiricose A5 (SA5) was detected in the brains by LC-MS analysis. SA5 at 10 μM significantly induced axonal growth after amyloid β induced axonal degeneration in cultured cortical neurons. In cultured cortical microglia, amyloid β increased inflammatory M1 microglia. After that, SA5 at 1 nM tended to increase M2 predominance but not significant. Continuous intracerebroventricular injection of SA5 at 10 μM significantly improved memory impairment in 5XFAD Alzheimer‘s disease model mice, but SA5 at 1 nM did not. SA5 injection at 10 μM significantly decreased degenerated axon in the perirhinal cortex of 5XFAD mice. DARTS analysis showed a candidate of direct binding protein with SA5.
Above results indicate that SA5 affects neurons, not microglia, in the brain, induces axonal growth, and then recovers memory in 5XFAD mice. Now, we are investigating whether the protein identified by DARTS analysis is involved in mechanisms of SA5.