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

Abstract

Ischemic stroke is a challenging disease with high mortality and disability rates, causing a great economic and social burden worldwide. During ischemic stroke, ionic imbalance and excitotoxicity, oxidative stress, and inflammation are developed in a relatively certain order, which then activate the cell death pathways directly or indirectly via the promotion of organelle dysfunction. Neuroprotection, a therapy that is aimed at inhibiting this damaging cascade, is therefore an important therapeutic strategy for ischemic stroke. Notably, phytochemicals showed great neuroprotective potential in preclinical research via various strategies including modulation of calcium levels and antiexcitotoxicity, antioxidation, anti-inflammation and BBB protection, mitochondrial protection and antiapoptosis, autophagy/mitophagy regulation, and regulation of neurotrophin release. In this review, we summarize the research works that report the neuroprotective activity of phytochemicals in the past 10 years and discuss the neuroprotective mechanisms and potential clinical applications of 148 phytochemicals that belong to the categories of flavonoids, stilbenoids, other phenols, terpenoids, and alkaloids. Among them, scutellarin, pinocembrin, puerarin, hydroxysafflor yellow A, salvianolic acids, rosmarinic acid, borneol, bilobalide, ginkgolides, ginsenoside Rd, and vinpocetine show great potential in clinical ischemic stroke treatment. This review will serve as a powerful reference for the screening of phytochemicals with potential clinical applications in ischemic stroke or the synthesis of new neuroprotective agents that take phytochemicals as leading compounds.

Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

“…The mechanism of the neuroprotective effects of flavonoids, including kaempferol, is associated with the modulation of autophagy [ 18 ]. Autophagy is a multistep process involving induction, phagophore formation, sequestration, autophagosome formation, and finally fusion of the autophagosome with a lysosome to form an autophagolysosome, which then induces either the death or survival pathway [ 19 ].…”

Neuroprotective Effect of Daidzein Extracted From Pueraria lobate Radix in a Stroke Model Via the Akt/mTOR/BDNF Channel

“…Phosphorylated CREB, an activated state of CREB, could up-regulate the expression of BDNF, while BDNF also promotes the activation of CREB through tropomyosin receptor kinase (Trk) B receptors (Zhang et al, 2012;Lan et al, 2014). According to an existing study, the repeated administration of Genistein (a monoterpene isoflavone) was found to improve CREB activity, up-regulate the BDNF expression, and protect the injured nerve of ischemic injury (Xu et al, 2021). Rapid release of BDNF contributed to reverse I/R-induced ischemic injury behaviors in rats .…”

Epigallocatechin Gallate Modulates Essential Elements, Zn/Cu Ratio, Hazardous Metal, Lipid Peroxidation, and Antioxidant Activity in the Brain Cortex during Cerebral Ischemia

“…Despite the numerous and continuous achievements over the years in exploring the mechanisms of EGCG underlying neuroprotection, it has not yet been elucidated so far whether the neuroprotective mechanism of EGCG is associated with the modulations of essential elements and hazardous metal during cerebral ischemic injury. A recent study reveals that cerebral ischemia-induced brain cell death is implicated with three dominant mechanisms and suggests that ionic perturbation is the first, followed by oxidative stress, and inflammation is the last one [ 21 ]. In fact, the occurrence of ionic perturbation is developed within a few minutes after ischemic insult [ 21 ].…”