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.

Polymer nanoparticles (NPs) increase resveratrol (Res) oral bioavailability in intracerebral hemorrhage (ICH) and the anti-ferroptosis mechanism of Res-NPs.

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Objective. Traditional Chinese medicine formula Kai-Xin-San (KXS) is used to treat psychiatric disorders, especially in anxiety and depression. However, the precise molecular mechanism of action remains unclear. In this study, we investigated the antidepressant effect of KXS on inhibiting inflammation and oxidative stress in corticosterone (CORT)-induced depression. Methods. The therapeutic efficacy of KXS was evaluated in a mouse model of depression induced by CORT. Behavioral tests were conducted to evaluate the effectiveness of KXS in treating depressive-like behavior. Nissl staining and β-galactosidase staining were used to assess the effects of KXS on neuronal injury in depressed mice. To screen key potential therapeutic targets of KXS, transcriptome sequences and data analysis were performed. Then, Iba1 immunofluorescence staining and their relative inflammatory factors mRNA expression were conducted to assess the effect of KXS in inhibiting microglial inflammation activation response. Concurrently, the measurement of 4-Hydroxynonenal (4-HNE) immunohistochemistry staining, malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were performed to evaluate the effect of KXS on anti-oxidative stress of depression in vivo. Besides, nitric oxide (NO), relative inflammatory factors mRNA expression, JC-1 staining, and ROS were used to evaluate the effect of KXS by lipopolysaccharide (LPS)/interferon-gamma (IFNγ)-induced BV2 cells. Results. KXS significantly relieved the depressive-like symptoms induced by CORT, as well as ameliorating the neuronal damage, which decreased microglia inflammatory activation response of IL-1β, IL-6, and tumor necrosis factor α (TNFα) in vivo or in vitro too. Transcriptome Sequencing and Data Analysis showed that KXS mainly by regulating immune system and transduction pathways decreased CORT-induced depression in mice. And showed that there were 19 Principal components and 10 genes in the main regulatory position with the strongest correlation in depression mice. Meanwhile, KXS effectively decreased senescence, the expression of 4-HNE, MDA content, and the production of ROS, while increasing the SOD activity in CORT-induced mice. Besides, KXS significantly reversed the mitochondrial membrane potential loss and excessive ROS production in LPS/IFNγ-induced BV2 cells. Conclusion. Our research suggested that KXS might protect depressed mice against CORT-induced neuronal injury by inhibiting microglia activation and oxidative stress.

Background: Intracerebral hemorrhage (ICH) is a severe type of stroke. Ferroptosis is a new form of regulated cell death, which plays an indispensable role in the pathological process of ICH. Curcumin (Cur), a widespread phenolic compound, is derived from the rhizome of Curcuma longa. It could attenuate hematoma volume and neurological injury in ICH. Nevertheless, its poor solubility in water, low oral bioavailability and difficulty in transporting across physiological barriers led to poor efficacy. Polymer nanoparticles (NPs) are widely used drug delivery matrix material with good biocompatibility, which are reported to improve the bioavailability and pharmacokinetic profiles of drugs. In this study, we utilized NPs to encapsulate Cur and analyzed the effect of Cur-NPs on Cur brain delivery and its therapeutic efficacy against ICH. Results: The spherical Cur-NPs had a particle size 127.31±2.73 nm, a PDI of 0.21±0.01 and a zeta potential of -0.25±0.02 mV. Cur-NPs could draw into Madin-Darby canine kidney (MDCK) cells through a number of nonspecific endocytosis mechanisms, mainly mediated via clathrin and plasma membrane microcapsules. Moreover, Cur-NPs tended to accumulate in the endoplasmic reticulum and lysosome. In a zebrafish model, Cur-NPs could transport across physiological barriers. In a C57BL/6 mice model, we found that Cur-NPs had more desirable improvements in Cur accumulation within the plasma and brain. Importantly, in an ICH mouse model, we confirmed that Cur-NPs were an effective treatment for ICH. Finally, Cur-NPs effectively inhibited ferroptosis caused by erastin in HT22 mouse hippocampal cells. Conclusion: Cur-NPs represent a potentially effective strategy to enhance Cur brain delivery and therapeutic efficacy in the treatment of ICH.