Baicalein cardioprotection via oxidant scavenging and akt-nitric oxide signaling: Identification of early reperfusion phase as the critical therapeutic window
Journal
American Journal of Chinese Medicine
Journal Volume
47
Journal Issue
5
Pages
1043-1056
Date Issued
2019
Author(s)
Li C.-Q.
Hsu C.-W.
Lee C.
Huang H.-H.
Yuan C.-S.
Vanden Hoek T.L.
Shao Z.-H.
Li J.
Abstract
Baicalein is a natural flavonoid with anti-oxidant activities protecting against ischemia/reperfusion (I/R) injury. Previous studies suggest that oxidative burst early after reperfusion accelerates cell death. We therefore investigated the critical therapeutic window of baicalein by examining the timing of baicalein treatment in relation to its oxidant modulating and cytoprotective effects. Using an established chick cardiomyocyte model of I/R, we administered baicalein at various time points after reperfusion and assessed cell viability and the profiles of reactive oxygen species (ROS), nitric oxide (NO), and Akt phosphorylation. Baicalein administered at the onset of reperfusion resulted in a concentration-dependent reduction of cell death (25 μM 48.2±1.9%, 50μM 43.8±1.5%, 100μM 36.6±2.1%, vs. I/R control 57.3±1.4%, all p0.05). Baicalein (100μM) timely and effectively scavenged ROS burst and enhanced NO production in the early reperfusion phase. Cotreatment with NO synthase (NOS) inhibitor l-NAME (200μM) partially abrogated the cytoprotective effect. Baicalein (100μM) given after reperfusion lost protective effect in a time-dependent manner with cytoprotection completely lost if >60min. Even with only 15-min delay after reperfusion, the ROS scavenging effect was abolished and the NO enhancing effect markedly reduced. The phosphorylation of Akt, an upstream regulator of eNOS, also diminished as the delay lengthened. In conclusion, baicalein treatment after reperfusion confers cardioprotection in a concentration- and time-dependent manner. The critical therapeutic window lies in the early reperfusion phase, during which ROS scavenging and Akt-eNOS mediated NO signaling are most effective.
SDGs
Type
journal article