Baicalin Inhibits Ferroptosis in Intracerebral Hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. To date, the exact etiology of ICH-induced brain injury is still unclear. Moreover, there is no effective treatment to delay or prevent disease progression currently. Increasing evidence suggests that ferroptosis plays a dominant role in the pathogenesis of ICH injury. Baicalin is a main active ingredient of Chinese herbal medicine Scutellaria baicalensis. It has been reported to exhibit neuroprotective effects against ICH-induced brain injury as well as reduce iron deposition in multiple tissues. Therefore, in this study, we focused on the protective mechanisms of baicalin against ferroptosis caused by ICH using a hemin-induced in vitro model and a Type IV collagenase-induced in vivo model. Our results revealed that baicalin enhanced cell viability and suppressed ferroptosis in rat pheochromocytoma PC12 cells treated with hemin, erastin and RSL3. Importantly, baicalin showed anti-ferroptosis effect on primary cortical neurons (PCN). Furthermore, baicalin alleviated motor deficits and brain injury in ICH model mice through inhibiting ferroptosis. Additionally, baicalin existed no obvious toxicity towards the liver and kidney of mice. Evidently, ferroptosis is a key pathological feature of ICH and baicalin can prevent the development of ferroptosis in ICH. As such, baicalin is a potential therapeutic drug for ICH treatment.

Cepharanthine Attenuates Early Brain Injury after Subarachnoid Hemorrhage in Mice via Inhibiting 15-Lipoxygenase-1-Mediated Microglia and Endothelial Cell Ferroptosis

“…More importantly, they reported that 15-HpETE-PE was catalyzed by ALOX15 as a ferroptotic signal in their TBI model [ 19 ]. The pharmacological inhibitor of ALOX15, baicalein, also showed neuroprotective effect in ICH and TBI models [ 41 , 42 ]. In this present study, we revealed that the protein level of ALOX15 started to increase at 24 h after SAH modeling and maintained a high level throughout the whole EBI period.…”

Bibliometric Analysis of Ferroptosis in Stroke From 2013 to 2021

“…Some natural products and traditional Chinese medicine-related content have also been confirmed to improve the prognosis of stroke by regulating ferroptosis. The baicalin, carthamin yellow, dauricine, (−)-epicatechin, kaempferol, and paeonol ameliorate neuronal ferroptosis in vitro or in vivo stroke models via regulating ACSL4, GPX4, TFR1, Fe 2+ , and NRF2 pathways ( Chang et al, 2014 ; Duan et al, 2021 ; Guo et al, 2021 ; Jin Z. L. et al, 2021 ; Peng et al, 2021 ; Yuan et al, 2021 ), which show great potential in the treatment of stroke. Treating MCAO rats with Naotaifang (a traditional Chinese herbal medicine compound) extract involves inhibition of acute cerebral ischemia-induced neuronal ferroptosis and neurobehavioral disorder through TFR1/DMT1 and SCL7A11/GPX4 pathways ( Lan et al, 2020 ).…”

Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage

“…et al, 2011 ), and reduce the pro-apoptotic proteins, Bax and caspase-3 ( Zhang Y. et al, 2015 ). Baicalin reportedly decreased protein expression of NF-κB P65, iNOS, COX-2, and MMP9 ( Xu et al, 2013 ; Liang et al, 2017 ; Chen et al, 2018 ), protected glutamine synthetase from ROS ( Song et al, 2020 ), and inhibited ferroptosis ( Duan et al, 2021 ). Ginsenosides are the main active components of ginseng, and more than 40 different monomer structures have been identified.…”