Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes

Abstract

Since flavonoids scavenge reactive oxygen species, they may potentially protect against ischemia/ reperfusion injury. This study compared the scavenging capacity of specific flavonoids towards different reactive oxygen species. Whether the differential oxidant scavenging capacity correlated with their protective efficacy in ischemia/reperfusion injury of cardiomyocytes was determined. The free radical scavenging capacity of five flavonoids (wogonin, baicalin, baicalein, catechin and procyanidin B 2 ) was analyzed using electron spin resonance spectrometry for 3 radicals: 1,1-diphenyl-2picrylhydrazyl (DPPH), superoxide and hydroxyl radical. A well-established chick cardiomyocyte model of ischemia (1 h)/reperfusion (3 h) was used to evaluate flavonoid-induced protection against ischemia/reperfusion injury in chronic treatment (pretreated 72 h and treated through ischemia/reperfusion) and acute treatment protocols (during ischemia/reperfusion or only at reperfusion). The cell viability was assessed by propidium iodide. The DPPH scavenging was most significant with catechin, followed by procyanidin B 2 , baicalein, baicalin, and wogonin. The superoxide scavenging was, similarly, most significant with catechin, followed by baicalein, procyanidin B 2 , and baicalin. For hydroxyl radical, only baicalein showed a significant scavenging capacity (> 50% reduction in ESR signal). For the cardiomyocyte studies, all flavonoids but wogonin showed protection against ischemia/reperfusion injury in the chronic treatment protocol. When flavonoids were administered only during ischemia/reperfusion, baicalein, procyanidin B 2 , and catechin significantly reduced cell death. If flavonoids were administered just at reperfusion, only baicalein and procyanidin B 2 had protective effects, and the efficacy was less. Flavonoids possess specific but differential radical scavenging capacity, which, in conjunction with the timing of treatment, affects their protective efficacy in cardiomyocytes exposed to ischemia/reperfusion.

Baicalein protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis through inhibition of reactive oxygen species production and CHOP induction

“…However, interestingly, we found that pretreatment with baicalein attenuated TG-or BFA-induced ROS accumulation ( Figure 6A and 6B) and MMP reduction (Figure 7). This result is in agreement with that of a previous report showing that baicalein is a potent anti-oxidant against cardiomyocytes ischemia/reperfusion injury (Chang et al, 2007). Therefore, we suggest that baicalein exerts an anti-oxidative effect against TG-or BFAinduced mitochondrial dysfunction and apoptosis.…”

“…We also found that baicalin was not able to reduce ER stress-induced ROS accumulation (data not shown). In agreement with our result, it was shown that the anti-oxidant potential of baicalin was attenuated as compared to that of baicalein (Chang et al, 2007). Moreover, it was also shown that cell permeability of baicalin was poor due to its glycoside group (Dai et al, 2008).…”

Luteolinidin Protects the Postischemic Heart through CD38 Inhibition with Preservation of NAD(P)(H)

“…Although luteolinidin protects the heart through its potent inhibition of CD38, it could also exert other beneficial effects. It has been suggested that flavonoids can be protective due to their antioxidant activity (Necas et al, 2006;Chang et al, 2007). In our experiments, the dose dependence of the protection (from 5 to 50 mM) argues for relatively high potency and low toxicity for luteolinidin.…”

Baicalin attenuates oxygen-glucose deprivation-induced injury by inhibiting oxidative stress-mediated 5-lipoxygenase activation in PC12 cells

“…Furthermore, baicalin exerts various effects [16][17][18][19] and can protect against ischemic injury [20][21][22][23] and inflammation [18,22,38] . One of the mechanisms of baicalin may include inhibition of 5-LOX activation in these disorders.…”

“…Therefore, ischemic 5-LOX activation can be regulated by both elevated intracellular calcium after excitotoxicity and the activated MAPK pathway after oxidative stress. Baicalin is one of the predominant flavonoids isolated from the dry roots of Scutellaria baicalensis Georgi (Huang Qin) with multiple pharmacological effects in peripheral organs and tissues [16][17][18][19] . Baicalin also exerts a protective effect on ischemic brain injury [20][21][22][23] .…”