Neuroprotective Effects Of Geniposide, The Main Active Component Of Gardenia Jasminoids Ellis And Its Molecular Mechanisms

The fruit of Gardenia jasminoids Ellis as an ingredient in traditional Chinese medicine, is an edible and medicinal resource. Gardenia jasminoids Ellis has a big production and a low availability in our country, people always only extract materials like pigment from Gardenia jasminoids Ellis, which makes serious problems of resource waste and environmental pollution. As a result, to rationally develop Gardenia jasminoids Ellis has important significance.Our previous work showed that geniposide, the main active component of Gardenia jasminoids Ellis, belongs to the class of compounds called the iridoids, demonstrated neuroprotective and neurotrophic effects with the activation of glucagon-like peptide 1 receptor(GLP-1R). But unfortunately, the molecular mechanisms keep to be explored. In this study, we investigate the effect of geniposide on the metabolism of Aβ and phosphorylation of tau protein in APP/PS1 transgenic mice and primary cultured cortical neurons. We also explored the realationship between Leptin signaling and the role of geniposide on the production of Aβ and phosphorylation of tau.The results suggested that treated with geniposide for 4 weeks could significantly decrease the production of Aβ1-42 and phosphorylated tau, and increase the protein levels of Leptin and its receptor in the brain tissue of APP/PS1 transgenic mice. To clarify the linkage between Leptin signaling and the effects of geniposide on the Aβ1-42 and phosphorylation of tau, we probed the role of LA, an antagonist for Leptin receptor, on the production of Aβ1-42 and tau phosphorylation induced by geniposide in primary cultured cortical neurons. Our data demonstrated that, similar as animal experiments, geniposide decreased the level of Aβ1-42 in a time-despendent manner, and decrease the phosphorylation of tau protein in primary cultured cortical neurons.And, geniposide also regulated the expression of Aβ cleave enzymes, including BACE1, PS1, and ADAM10, geniposide also enhance the phosphorylation of GSK-3β in primary cultured cortical neurons. Furthermore, preincubation with LA could prevent the effect of geniposide on the phosphorylation of JAK2-STAT3, the key signaling molecules of the downstream of Leptin signaling the expression of BACE1, PS1, and ADAM10, and phosphorylation of GSK-3β in the cortical neurons. All these data suggested that geniposide might be useful to treatment with Alzheimer’s disease, and this effect was associated with its role on the Leptin signaling, which might be helpful to supply more experimental evidence for the use of geniposide on the neuroprotection, and the use of Gardenia jasminoids Ellis in future.