Quercetin Might Promote Autophagy in a Middle Cerebral Artery Occlusion-Mediated Ischemia Model: Comments on Fawad-Ali Shah et al.

Abstract

The recent paper by Fawad-Ali Shah on this journal describes the role of the flavonoid quercetin in a cerebral ischemia model induced in adult Sprague-Dawley male rats by middle cerebral artery occlusion (MCAO) [1]. The authors reported that quercetin in MCAO-induced ischemia modulated the expression of the enzymes isocitrate dehydrogenase [NAD + ] (which is present in two isoforms, EC. 1.1.1.41 and EC 1.1.1.42), adenosyl-homocysteinase (EC, 3.3.1.1), pyruvate kinase (EC 2.7.1.40), ubiquitin carboxy terminal hydrolase L1 (EC, 3.1.2.15), besides to the proteins heat shock protein 60 (hsp60) and collapsin response mediator protein 2 (CRMP2) [1]. Actually, many further important proteins are upregulated (and some of them down-regulated) by quercetin in the reported MCAO model [1]. Following Fawad-Ali Shah et al.'s paper, we hypothesized that the up-or down-regulation of the many specific proteins by quercetin might deal with the occurrence of an autophagic mechanism, directly or indirectly promoted by the flavonoid itself in the MCAO-induced ischemia [1]. Autophagy is a regular, physiological process adopted by cells to disassembly dysfuncional, damaged or unnecessary components, including organelles such as mitochondria (mitophagy). It usually involves a cascade of events starting with the phosphorylation of beclin-1 (the mammalian homologue of Atg6) [2]. The cell self-digesting mechanism that is responsible for the removal of long-lived proteins * Salvatore Chirumbolo

Neuroprotective Phytochemicals in Experimental Ischemic Stroke: Mechanisms and Potential Clinical Applications

“…Quercetin is often used as a dietary supplement due to its good antioxidant and anti-inflammatory activities. In experimental ischemic stroke studies, quercetin was found to reduce the brain injuries of pMCAO rats via multiple mechanisms, including antiapoptosis, promotion of autophagy, regulation of energy metabolism, and upregulation of PP2A (protein phosphatase 2) [180][181][182]187]. Recently, quercetin was subjected to a clinical trial to evaluate its effect on improving the cerebral blood flow in the aged population (NCT01376011).…”

Quercetin Alleviated Inflammasome-Mediated Pyroptosis and Modulated the mTOR/P70S6/P6/eIF4E/4EBP1 Pathway in Ischemic Stroke

“…We recently revealed a multimechanistic mechanism by which quercetin affects the expression of numerous proteins in an ischemic brain [ 19 ]. In response, Chirumbolo et al submitted an editorial response that quercetin may induce autophagy in brain ischemia [ 20 ]. The study of autophagy behavior in ischemic stroke is a complex issue due to conflicting findings in the published studies.…”

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Buyang Huanwu Decoction in the Treatment of Ischemic Stroke

“…It was found that quercetin could pass through the blood-brain barrier with the highest passage rate [42]. A research showed that quercetin had effects of antioxidant stress and promoting autophagy, which was helpful for the prevention and treatment of stroke [43,44]. In addition, quercetin could also regulate protein phosphatase 2A subunit B (PP2A) to produce significant neuroprotective effects on rats with cerebral ischemia-reperfusion injury and HT22 cell model of glutamate injury [45].…”