Rea regulates microglial polarization and attenuates neuronal apoptosis via inhibition of the NF‐κB and MAPK signalings for spinal cord injury repair

Xiao, Shining; Wang, Chenggui; Yang, Qingqing; Xu, Haibin; Lu, Junyan; Xu, Kan

doi:10.1111/jcmm.16220

Cited by 34 publications

(30 citation statements)

References 53 publications

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“…A large number of studies have shown that reducing central nervous system inflammation and peripheral inflammatory cell infiltration (e.g., macrophage) can significantly reduce secondary damage and promote functional recovery following SCI [16, 43]. After SCI, microglia/macrophages not only polarize into M1 cells causing inflammation, but they may also partially polarize into M2 cells, which have anti-inflammatory properties [5, 54]. The polarized orientation of microglia/macrophages after SCI is strongly skewed toward the M1 phenotype [16].…”

Section: Discussionmentioning

confidence: 99%

“…However, there are no effective treatments for SCI. The pathological process of SCI can be divided into primary and secondary injuries [4,5]. Primary SCI, which includes in situ structural damage, vascular rupture in the lesion area, and local bleeding around the lesion area, is caused by traumatic events (e.g., vehicle accidents or falling from a building) [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that anti-neuroinflammatory medications and anti-apoptotic therapies have been shown to improve behavioral functions in a variety of animal models of SCI [5, 11]. However, few medications can enhance the M2/M1 polarization ratio in microglia/macrophages and prevent neuronal death.…”

Section: Introductionmentioning

confidence: 99%

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Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Xiao

Zhong

Yang

et al. 2022

Preprint

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Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Au in SCI have not been reported. We showed that Au can promote functional recovery after SCI. Recovery may occur through the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway to promote M2/M1 polarization in microglia and inhibit mitochondrial dysfunction to reduce neuronal apoptosis. These biochemical changes result in reduced secondary injury and facilitate axon regeneration. Therefore, Au may be a promising post-SCI therapeutic medication.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Xiao

Zhong

Yang

et al. 2022

Preprint

Self Cite

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“…Flavonoids are the active ingredient extracted from these two Materia Medica, and they are the multi-functional phytochemical presenting substantial characteristics that can be exploited for therapeutic agents targeting on various diseases, pharmaceutically [35]. Xiao et al (2021) found that avonoid-enriched RR extract shown the neuronal protective properties by suppressing of the NF-κB and MAPK signaling pathway [36]. Xie and Du (2011) published the similar results, they found RR methanol extraction shown the therapeutic functions for in ammatory treatment by blocking TNF-α, IL-1β, IL-6 and IL-15 productions [37].…”

Section: Discussionmentioning

confidence: 99%

Zhuanggu Guanjie herbal formula mitigates osteoarthritis via NF-κB transduction mechanism in vitro

Gong¹,

Zheng²,

Zhou³

et al. 2021

Preprint

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BackgroundZhuanggu Guanjie herbal formula, a famous Chinese prescription, which is commonly applied for mitigating bone-related problems, clinically. According to the China Pharmacopeia (CP, 2020), this herbal formula includes 12 raw materials, and the major components are Rehmanniae Radix (RR) and Psoraleae Fructus (PF). The anti-osteoarthritis properties of this herbal prescription are well-documented in CP (2020). However, the working mechanism of this ancient herbal formula has not been elucidated. Therefore, we would like to probe the anti-osteoarthritis pharmaceutical values of this ancient herbal prescription.Materials and methodsThe differentiated ATDC5 cells were employed in the following experiments. In the present study, the involvements of cytokine levels and hallmark proteins reflecting inflammatory responses in Zhuanggu Guanjie Capsule (ZGC)-induced differentiated cells were detected by RT-PCR, flow cytometer, western blot and laser confocal assays.ResultsThe cytokines and inflammation-specific proteins, i.e. interleukin (IL)-6, tumor necrosis factor- (TNF-) and inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostaglandin synthesis E2 (PGES-2) were robustly declined after incubating with ZGC for 48 hours, and the attenuation levels were in a dose-dependent manner. Furthermore, ZGC could also block NF-B translocation from cytosol to nucleus and which has been verified by the laser confocal microscope.ConclusionsThe in vitro studies have clarified the anti-osteoarthritis properties of ZGC and the working mechanism involved, and this herbal formula shed light on osteoarthritis treatment.

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“…Secondary SCI is caused by pathological changes after primary injury, which can result in inflammation, oxidative stress, glial scar formation, neuronal apoptosis, and neuronal necrosis (Anjum et al, 2020;Wang et al, 2020d). Recently, SCI models induced by lipopolysaccharide (LPS) are widely used to explore SCI pathogenesis and find new therapeutic medicine to treat SCI (Xiao et al, 2021).…”

Section: Spinal Cord Injurymentioning

confidence: 99%

Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

Chen

Lai

Wang

et al. 2021

Front. Mol. Neurosci.

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Microglia and astrocytes maintain tissue homeostasis in the nervous system. Both microglia and astrocytes have pro-inflammatory phenotype and anti-inflammatory phenotype. Activated microglia and activated astrocytes can contribute to several neurological diseases. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two groups of non-coding RNAs (ncRNAs), can function as competing endogenous RNAs (ceRNAs) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). LncRNAs and circRNAs are involved in various neurological disorders. In this review, we summarized that lncRNAs and circRNAs participate in microglia dysfunction, astrocyte dysfunction, neuron damage, and inflammation. Thereby, lncRNAs and circRNAs can positively or negatively regulate neurological diseases, including spinal cord injury (SCI), traumatic brain injury (TBI), ischemia-reperfusion injury (IRI), stroke, neuropathic pain, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), and Alzheimer’s disease (AD). Besides, we also found a lncRNA/circRNA-miRNA-mRNA regulatory network in microglia and astrocyte mediated neurological diseases. Through this review, we hope to cast light on the regulatory mechanisms of lncRNAs and circRNAs in microglia and astrocyte mediated neurological diseases and provide new insights for neurological disease treatment.

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Rea regulates microglial polarization and attenuates neuronal apoptosis via inhibition of the NF‐κB and MAPK signalings for spinal cord injury repair

Cited by 34 publications

References 53 publications

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Zhuanggu Guanjie herbal formula mitigates osteoarthritis via NF-κB transduction mechanism in vitro

Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

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