Background:

Anatabine, an alkaloid with a chemical structural similarity to nicotine, is a minor tobacco alkaloid produced in plants of the Solanacea family including tobacco, green tomatoes, peppers and eggplants [1]. (R,S)-Anatabine is an Aβ inhibitor [1].

Aβ peptides play a dominant role in the development of Alzheimer's disease. Natural soluble Aβ oligomers and more specifically Aβ dimers isolated from Alzheimer's disease brains have been involved in inducing tau hyperphosphorylation and neuritic degeneration, which results in the accumulation of Aβ oligomers to the neurofibrillary degeneration observed in Alzheimer's disease [1].

In vitro: Anatabine dose-dependently lowered Aβ1-40 and Aβ1-42 levels and reduced sAPPβ production without any effects on sAPPα levels. Anatabine lowered Aβ production by mainly impacting the β-cleavage of APP. Anatabine lowered NFκB activation. Anatabine inhibited BACE-1 transcription and reduced BACE-1 protein levels in human neuronal like SHSY-5Y cells. (R,S)-Anatabine also dose dependently inhibits NF-κB activation [1].

In vivo: In a transgenic mouse model of Alzheimer's disease, acute treatment with anatabine for 4 days significantly lowered brain soluble Aβ1-40 and Aβ1-42 levels [1].

Reference:
[1] Paris D, Beaulieu-Abdelahad D, Bachmeier C, et al.  Anatabine lowers Alzheimer's Aβ production in vitro and in vivo[J]. European journal of pharmacology, 2011, 670(2): 384-391.