Neuroprotective Effects of Quercetin on Ischemic Stroke: A Literature Review

Abstract

Ischemic stroke (IS) is characterized by high recurrence and disability; however, its therapies are very limited. As one of the effective methods of treating acute attacks of IS, intravenous thrombolysis has a clear time window. Quercetin, a flavonoid widely found in vegetables and fruits, inhibits immune cells from secreting inflammatory cytokines, thereby reducing platelet aggregation and limiting inflammatory thrombosis. In pre-clinical studies, it has been shown to exhibit neuroprotective effects in patients with ischemic brain injury. However, its specific mechanism of action remains unknown. Therefore, this review aims to use published data to elucidate the potential value of quercetin in patients with ischemic brain injury. This article also reviews the plant sources, pharmacological effects, and metabolic processes of quercetin in vivo, thus focusing on its mechanism in inhibiting immune cell activation and inflammatory thrombosis as well as promoting neuroprotection against ischemic brain injury.

Sepsis-induced AKI: From pathogenesis to therapeutic approaches

“…Quercetin, a plant flavonoid, has antioxidant, anti-fibrotic, anti-inflammatory, anti-cancer and neuroprotective effects ( Ozsoy Gokbilen et al, 2022 ; Zhang et al, 2022 ). A previous study found that resveratrol/quercetin induced activation of SIRT1, resulting in the induction of p53 deacetylation.…”

Quercetin’s Effects on Glutamate Cytotoxicity

“…Quercetin glycosides are found in higher circulating concentrations, hypothesized to be due to sodium-dependent glucose transporters in the GI epithelium [ 38 ]. Although quercetin and its metabolites have been studied and calculated in circulation, it has been observed that quercetin’s bioavailability is too low for quercetin’s health benefits to take effect in the brain, especially given that the blood–brain barrier is impermeable to quercetin [ 40 ]. Therefore, overcoming quercetin’s low bioavailability and half-life will be critical in the application of its beneficial in vivo effects to attenuating GE.…”

“…Many of the cellular conditions during GE activate apoptotic mechanisms by various methods, most of which can be counteracted by quercetin, as seen in Figure 4 , showing quercetin to be a beneficial therapy against GE. Firstly, quercetin has been shown to upregulate PI3K/AKT pathways in ischemic rat cells, leading to decreased expressed, apoptotic caspase 3 enzymes [ 40 ]. Quercetin can direct inhibition and downregulation of caspase 3 activation, which protects cells from intrinsic apoptosis mechanisms [ 56 , 57 , 58 , 59 ].…”

“…The degradation of the membrane and the release of lysosomal contents add to the oxidative stress and cellular damage occurring during the ischemia and GE [ 44 , 62 ]. Quercetin’s inhibition of Bax, activation of Bcl-2, and decrease in Ca 2+ concentrations that lead to the reduction of ROS and RNS provide neuronal protection and the potential to halt cell death during LMP, as shown in Figure 4 [ 40 ].…”

“…Nanoencapsulated quercetin has been shown to reduce the expression of inducible nitric oxide synthase (iNOS) in ischemic rat hippocampus, an effect associated with downregulated synthesis of RNS and upregulated levels of glutathione, SOD1, and HO-1 [ 64 ]. Studies on reperfusion after ischemia in the brains of rats have shown decreased levels of malondialdehyde and myeloperoxidase, which downregulated the production of NO, ROS, and lipid peroxidation [ 40 ]. Figure 5 and Table 2 work to summarize quercetin’s protective effects against cell death caused by oxidative damage during GE.…”