Flavonoids in Brain Ischemia-Reperfusion and their Effect on Kinases as Signaling Pathway Activity

Brain ischemia-reperfusion injury (CIRI) refers to brain ischemia that leads to cellular dysfunction and cell death after a certain period, and ischemic damage is rescued by providing blood supply and reperfusion. And then, reperfusion includes components such as ion imbalance, mitochondrial dysfunction, oxidative stress, neuroinflammation, Ca²⁺ overload, and apoptosis, which do not cause tissue damage. Autophagy also occurs in CIRI due to oxygen deficiency, and autophagy has been shown to protect cells from ischemic injury. Flavonoids are a class of essential and diversified secondary plant metabolites found in different concentrations in leaves, flowers, roots, and fruits. Various studies have shown that flavonoids have healing qualifications such as anti-inflammatory, antimutagenic, anticarcinogenic, and antimicrobial. We aim to determine how flavonoids may affect signaling pathways and kinases in rats with CIRI. The results show that the activity of JAK2/STAT3, NF-κB, RhoA/ROCK, JNK-p38, and cAMKII signaling pathways increases under CIRI, and the PI3K/Akt/mTOR signaling pathway is suppressed. Studies using various flavonoids (kaempferol, chrysin, naringin, naringenin, quercetin, wogonin) have shown a neuroprotective effect by reversing the situation in signaling pathways during CIRI damage.