Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

Abstract

Retinal ischemia is a common cause of many retinal diseases, leading to irreversible vision impairment and blindness. Excessive neuroinflammation, including microglial activation and T-cell responses, has been identified as a critical factor associated with neurodegeneration in retinal ischemia. Baicalein is a natural flavonoid reported to have broad anti-inflammatory and neuroprotective bioactivities. Herein, the effects of baicalein on microglia activation in vitro and in vivo were investigated. We found that baicalein exhibited robust anti-inflammatory effect on cultured human and mouse microglia, as demonstrated by decreased induction of pro-inflammatory cytokines and the phosphorylation of phosphoinositide 3-kinase (PI3K) and nuclear factor kappa B (NFκB). Proteomic analysis further unraveled baicalein’s effect on modulating IL-17 signaling pathways and its upstream regulator IL-1β. Intravitreal administration of baicalein in the mouse model of retinal ischemia/reperfusion (I/R) injury attenuated microglial activation and retinal T-cell infiltration, particularly the T helper 17 cells. Additionally, baicalein was shown to exert neuroprotective effects by significantly reducing the retinal ganglion cell (RGC) loss after I/R injury, leading to an improved retinal function and spatial vision. These results suggest that baicalein, a natural flavonoid, acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that baicalein could be a potential therapeutic agent against currently incurable degenerative retinal diseases.

Electrical stimulation alters DNA methylation and promotes neurite outgrowth

“…To study the functional effect of ES in the ONC model, electroretinogram positive scotopic threshold response (pSTR) were recorded 27 . Mice were dark‐adapted overnight and anesthetized with an intraperitoneal injection of ketamine (120 mg/kg)/xylazine (20 mg/kg).…”

Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure

“…Using episcleral vein occlusion, a significant loss of RGCs and downregulation of PA2G4 expression have been shown in aged rats receiving cauterization when compared with controls [85]. Recently, the neuroprotective effects of Ba against retinal functional and morphological damages resulting from retinal ischemia reperfusion injury have also been demonstrated [86]. It was found that Ba alleviates the expression of proinflammatory cytokines including TNF-α, IL-6, and IL-1β in mouse microglia, supporting its biomedical significance for glaucoma treatment as elevated levels of TNF-α, IL-6, and IL-1β are observed in the TM of glaucoma patients [87].…”

Natural products: protective effects against ischemia-induced retinal injury

“…The therapeutic potential of natural herbal treatments for ischemic retinal damage has become increasingly evident in recent years. These medicines, including Scutellaria , lutein, and wolfberry, have antioxidant, anti-inflammatory, and anti-excitotoxic properties and can maintain the permeability of the retinal blood supply ( Li et al, 2009 ; He et al, 2014 ; Pan et al, 2022 ). In addition, various natural extracts, such as resveratrol, Ginkgo biloba extract, and curcumin, have been shown to protect the CNS and exhibit neuroprotective properties ( Yuan et al, 2014 ; Wang et al, 2017a ; Luo et al, 2020 ).…”

“…Scutellaria baicalensis is the main component of many traditional Chinese medicines, and its safety and efficacy in clinical applications have been demonstrated. Baicalin exerts potent anti-inflammatory effects by reducing the induction of proinflammatory cytokines and inhibiting PI3K/NF-κB phosphorylation ( Pan et al, 2022 ). Oroxylin A is a flavonoid that regulates nuclear factor E2-related factor 2 (Nrf2) and its antioxidant enzymes NAD(P)H quinone oxidoreductase 1 and home oxidoreductase 1 (HO-1).…”