High-Throughput Screening of Antioxidant Drug Candidates from Natural Antioxidants with a “Zero” Intrinsic Fluorescence Peroxynitrite Sensing Precursor

The fluorescence high-throughput screening method is
of importance
for new antioxidant drug candidate discovery for the treatment of
serious hepatorenal syndrome, which displayed an obvious upregulated
peroxynitrite level. However, most of the current ONOO– probes possessed incomplete fluorescence quenching efficiency, which
can result in non-negligible probe inherent fluorescence. Hence, we
utilized the probe conjugated structure disruption strategy to construct
hydrogenation phosphorus-substituted rhodamine (H–PRh) with “zero” probe inherent fluorescence character.
Based on the precursor, a series of natural products were screened
for identifying antioxidant drug candidates. Luteolin was screened
out by activating the Sirt1-Nrf2-HO-1 signaling pathway to regulate
the accumulation of ONOO– in the hepatorenal syndrome.
Overall, the “zero” probe inherent fluorescence ONOO– sensor constructed here applies for a promising and
versatile toolbox for illuminating the ONOO–-related
pathological process in the hepatorenal syndrome. Besides, this strategy
of constructing highly sensitive sensors could serve as a valuable
reference for further fluorescent probes.