Conclusion
Nar could increase the ROS elimination and decrease eNOS uncoupling, subsequently upregulate the NO bioavailability and endothelial function by activating AMPKα/Sirt1 signaling pathway.
Methods
After ruling out the NMDA-R1 mediated pathway, RNA-Seq, a novel transcriptomic technique uncovered AMPK signaling pathway was identified as the mechanism with which Nar corrects ED. Further in vivo and in vitro tests validated the role of Nar against ED.
Results
In particular, Nar activates AMPKα/Sirt1 signaling pathway, which restores mitochondrial Ca2+ balance and ultimately lowered production of reactive oxygen species (ROS). Activated AMPKα/Sirt1 signaling pathway also up-regulates endothelial nitric oxide synthase (eNOS) activity, and then increasing the production of nitric oxide (NO), ultimately ameliorating ED.