Timosaponin A3 and Sarsasapogenin inhibit nuclear factor-kB and p38 signaling in TNF-a stimulated BV-2 microglia cells

Anemarrhena asphodeloides Bunge (AA, family Liliaceae), which contains steroidal saponins, such as timosaponin AIII (TA3) and sarsasapogenin (SS), has been used as an antipyretic, anti-inflammatory, anti-diabetic, and antidepressant in traditional Chinese medicine. In our previous study, TA3 and SS improved memory impairment induced by scopolamine in mice. AA and its main constituents have been reported to improve memory by elevating low muscarinic acetylcholine receptor density and inhibiting acetylcholine esterase in the brain. Recently, it is suggested that an inflammatory response mediated by the activation of microglia is a key event in the early stages of the neurodegenerative diseases. Therefore, we investigated the inhibitory effect of TA3 and SS in TNF-α stimulated microglia and neuroblastoma cells. TNF-α activated NF-κB and pp38 signaling in these cells. The treatment with TA3 and SS inhibited the activation of the NF-κB and pp38 signaling in BV-2 microglial cells as well as in SK-N-SH neuroblastoma cells. Of them, SS more potently inhibited them than TA3. These results suggest that TA3 and SS may have the therapeutic potential for various neurodegenerative diseases caused by inflammation.

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