https://www.ncbi.nlm...les/PMC6829632/
The drug was adminsitered through IV with fisetin either at 0-3 hours or 3-5 hours after incident or without fisetin again in either over both time intervals. Those patientts taking the drug with fisetin, conintued for 7 days with just fisetin, presumably intravenously
Measurements are taken of MMP-2, MMP-3 and c-reactive protein. Reduced serum levels of all three correlate with favourable outcomes. And too, fisetin correlates strongly with low levels of MMP-2, MMP-3 and c-reactive protein.
The use of fisetin when adminstered in the first 3 hours with rt-PA, appears to offer no additional benefit over rt-PA, nor too the subsequent daily administration of fisetin for one week. Also, 7 days of fisetin adminstration appears to offer no additional benefit following the 3-5 hour fisetin and rt-PA group.
Despite the evidence of a relationship between low levels of CRP, MMP-2, MMP-9 and favourable outcomes, fisetin+rt-PA provides no benefit to rt-PA alone despite the combination producing still lower marker levels during that window.
Fisetin does though come into its own during that 3-5 hour window, around halving the worst outcome group compared to the drug alone after 24 hours, which is approximately retained after 7 days. And around a roughly 40% improvement in favourable outcomes after 24 hours, too roughly retained after 7 days.
It would be interesting to study fisetin exclusively in a group where treatment with rt-PA had lapsed at post 5 hours, say, compared to no treatment, and if proven efficacious, a trial pitting fisetin against rt-PA in the 3-5 hour window would be reasonable, especially given rt-PA's side effects after 3 hours.
So a promising clinical trial indicating fisetin could be used to improve outcomes in stroke patients, and too human data demonstrating IV Fisetin reducing serum levels of markers including c-reactive protein.
It would seem that during the window when Recombinant tissue plasminogen activator (rt-PA) is most effective, fisetin appears to add no benefit, presumably, I guess, it can only at best create no better expression than the drug at those markers. But after that window closes, when the drug is less effective, fisetin, it would appear is effective at lowering said markers, where rt-PA doesn't, and when unpleasant risk factors increase in using the drug.
