Geniposide attenuates the level of Aβ via enhancing leptin signaling in cellular and APP/PS1 transgenic mice.

An large body of evidence indicates that leptin has protective role against Alzheimer's disease, where it reduces β-amyloid (Aβ) production in both cell culture and animal models. Our previous studies revealed that geniposide could attenuate the production of Aβ and antagonize the neurotoxicity of Aβ in neurons. However, the mechanism that underlies these effects remains to be clarified. To investigate whether leptin signaling is involved in regulating the production of Aβ by geniposide, we treated primary neurons with leptin antagonist (LA), and determined the influence of LA on the activities of leptin signaling molecules and the expressions of secretases associated with the production of Aβ. The finding showed that, accompanied with the inhibition on the level of Aβ in primary neurons and APP/PS1 transgenic mice, geniposide induced the phosphorylation of JAK2 and STAT3, regulated the expression level of α- and β-secretase, and all of these could be prevented by the pre-incubation with LA. The results of this study suggest that geniposide may regulate the production of Aβ via leptin signaling.