Diarylpropionitrile

Diarylpropionitrile (DPN) is a non-steroidal estrogen receptor β(ERβ) selective ligand, demonstrates the neuroprotective effects against 10 0M Aβ1-42-induced oxidative stress and inflammation in primary rat cortical cell culture; (1-100 nM) significantly decreases neuronal cell death by increasing cell viability through a significant attenuation in the reactive oxygen species level, downregulation of pro-apoptotic activated caspase-3 and Bax, and upregulation of anti-apoptotic Bcl-2; decreases the expression levels of IL-1β and IL-6; inhibits medulloblastoma development via anti-proliferative and pro-apototic pathways.(In Vitro):DPN has a 70-fold ERα relative binding affinity selectivity, and it is a full ERα agonist with a 78-fold ERα potency selectivity (EC50=0.85 nM for ERβ; EC50=66 nM for ERα).DPN (10 nM) prevents morphological alterations from Aβ1-42 (10 μM)-induced toxicity in cultured cortical neurons.DPN (0.1-100 nM) decreases ROS levels in a non-dose response manner.DPN (0.1-100 nM) significantly reduces Aβ1-42-stimulated expression of Bax in a non-dose dependent manner.DPN (0.1-100 nM) reduces activated IL-1 levels induced by Aβ1-42 treatment on cultured cortical neurons.DPN (0.1-100 nM) suppresses the Aβ1-42-upregulated phosphorylation of JNK and p38.(In Vivo):DPN (10 μg; s.c.; daily; for 11 days) increases swimming and decreases immobility in the FST, and increases TPH protein expression in the dorsal raphe nucleus (DR) in rat model.