Baicalin facilitates remyelination and suppresses neuroinflammation in rats with chronic cerebral hypoperfusion by activating Wnt/β-catenin and inhibiting NF-κB signaling

Xiao, Yining; Guan, Tianyuan; Yang, Xiaofeng; Xu, Jing; Zhang, Jiawei; Qi, Qianqian; Teng, Zhenjie; Dong, Yanhong; Gao, Yaran; Li, Meixi; Meng, Nan; Lv, Peiyuan

doi:10.1016/j.bbr.2023.114301

Cited by 16 publications

(4 citation statements)

References 58 publications

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“…In support of this, previous studies have identified Wnt pathway components as VEGF signaling targets (Li et al 2021). Alternatively, NRP-mediated Wnt pathway inhibition could be achieved through binding partner-dependent regulation of NF-κβ signaling, which antagonizes Wnt signaling (Xiao et al 2023). Another possible explanation for NRP-mediated Wnt antagonism could be through the Tyrosine Kinase, FER.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation

Hoard,

Liu,

Cadigan

et al. 2024

Preprint

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Precise control of morphogen signaling levels is essential for proper development. An outstanding question is: what mechanisms ensure proper morphogen activity and correct cellular responses? Previous work has identified Semaphorin (SEMA) receptors, Neuropilins (NRPs) and Plexins (PLXNs), as positive regulators of the Hedgehog (HH) signaling pathway. Here, we provide evidence that NRPs and PLXNs antagonize Wnt signaling in both fibroblasts and epithelial cells. Further,Nrp1/2deletion in fibroblasts results in elevated baseline Wnt pathway activity and increased maximal responses to Wnt stimulation. Notably, and in contrast to HH signaling, SEMA receptor-mediated Wnt antagonism is independent of primary cilia. Mechanistically, PLXNs and NRPs act downstream of Dishevelled (DVL) to destabilize β-catenin (CTNNB1) in a proteosome-dependent manner. Further, NRPs, but not PLXNs, act in a GSK3b/CK1-dependent fashion to antagonize Wnt signaling, suggesting distinct repressive mechanisms for these SEMA receptors. Overall, this study identifies SEMA receptors as novel Wnt pathway antagonists that may also play larger roles integrating signals from multiple inputs.

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Section: Discussionmentioning

confidence: 99%

Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation

Hoard,

Liu,

Cadigan

et al. 2024

Preprint

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“…Baicalein and baicalin are the main active ingredients in the e cacy of Scutellaria baicalensis, and baicalin is a glycoside compound formed by the combination of baicalein and a molecule of glucuronic acid, both of which are present in Scutellaria baicalensis. Previous studies by our group have con rmed that baicalin can promote myelin regeneration and inhibit neuroin ammation in rats with chronic cerebral insu ciency of perfusion [10]. Whether baicalein has an ameliorative effect on cognitive impairment in VD, and whether its mechanism is related to the inhibition of in ammatory response and regulation of intestinal microbiota has not yet been reported.…”

Section: Introductionmentioning

confidence: 89%

Baicalein suppresses neuroinflammation in vascular dementia rats by inhibiting TLR4/MyD88/NF-κB signaling pathway and regulating intestinal microbiota

Song,

Li,

Kang

et al. 2023

Preprint

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Neuroinflammation induced by chronic cerebral hypoperfusion (CCH) plays a crucial role in the pathophysiologic mechanisms of vascular dementia (VD). A growing body of research has found that intestinal microbiota is associated with a variety of central nervous system disorders and that there is a relationship between intestinal microbiota dysbiosis and cognitive dysfunction and inflammatory responses. Baicalein belongs to the class of flavonoids and has a variety of biological functions, including anti-inflammatory, antioxidant and anti-apoptotic. Baicalein has a significant improvement in memory and learning, and can be used as a potential drug for the protection and treatment of central nervous system disorders. Whether baicalein has an ameliorative effect on cognitive impairment in VD, and whether its mechanism is related to the inhibition of inflammatory response and regulation of intestinal microbiota has not been reported. We used bilateral common carotid artery occlusion (BCCAO) to establish a VD rat model. Morris water maze (MWM) test showed that baicalein improved cognitive dysfunction in VD rats. We applied HE staining, immunofluorescence and ELISA to observe that baicalein treatment significantly improved CCH-induced neuronal damage in the CA1 region of the hippocampus, and reduced glial cell activation and release of pro-inflammatory factors. Western blot showed that baicalein inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway in VD rats. We applied 16S rDNA sequencing to analyze the composition of the intestinal microbiota. The results showed that baicalein modulated the diversity and composition of the intestinal microbiota, and suppressed the relative abundance of inflammation-associated microbiota in VD rats. In conclusion, this study found that baicalein ameliorated cognitive impairment, attenuated hippocampal inflammatory responses, inhibited the TLR4/MyD88/NF-κB signaling pathway, and modulated intestinal microbiota in VD rats.

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“…Baicalin also promotes the activation of the Wingless-related integration site/Dickkopf-1 (Wnt/DKK1) pathway, potentially mitigating AS progression ( 61 ). Baicalin can also decrease the levels of inflammatory factors by promoting the phosphorylation of glycogen synthase kinase 3β (GSK3β), enhancing β-catenin expression and nuclear translocation, which is associated with the Wnt pathway ( 62 ). In summary, these findings underscore baicalin’s role in attenuating inflammatory responses, thereby decreasing the degree of AS progression.…”

Section: Immuno-modulatory Features Of Baicalin In Asmentioning

confidence: 99%

Immuno-modulatory role of baicalin in atherosclerosis prevention and treatment: current scenario and future directions

Wang,

Huang,

Liang

et al. 2024

Front. Immunol.

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Atherosclerosis (AS) is recognized as a chronic inflammatory condition characterized by the accumulation of lipids and inflammatory cells within the damaged walls of arterial vessels. It is a significant independent risk factor for ischemic cardiovascular disease, ischemic stroke, and peripheral arterial disease. Despite the availability of current treatments such as statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and lifestyle modifications for prevention, AS remains a leading cause of morbidity and economic burden worldwide. Thus, there is a pressing need for the development of new supplementary and alternative therapies or medications. Huangqin (Scutellaria baicalensis Georgi. [SBG]), a traditional Chinese medicine, exerts a significant immunomodulatory effect in AS prevention and treatment, with baicalin being identified as one of the primary active ingredients of traditional Chinese medicine. Baicalin offers a broad spectrum of pharmacological activities, including the regulation of immune balance, antioxidant and anti-inflammatory effects, and improvement of lipid metabolism dysregulation. Consequently, it exerts beneficial effects in both AS onset and progression. This review provides an overview of the immunomodulatory properties and mechanisms by which baicalin aids in AS prevention and treatment, highlighting its potential as a clinical translational therapy.

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Baicalin facilitates remyelination and suppresses neuroinflammation in rats with chronic cerebral hypoperfusion by activating Wnt/β-catenin and inhibiting NF-κB signaling

Cited by 16 publications

References 58 publications

Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation

Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation

Baicalein suppresses neuroinflammation in vascular dementia rats by inhibiting TLR4/MyD88/NF-κB signaling pathway and regulating intestinal microbiota

Immuno-modulatory role of baicalin in atherosclerosis prevention and treatment: current scenario and future directions

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