Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs–NF–κB signaling pathway and pyroptosis after secondary spinal cord injury

Liu, Zhongyuan; Yao, Xinqiang; Sun, Baihui; Jiang, Wangsheng; Liao, Congrui; Dai, Xiangheng; Chen, Yu; Chen, Jianting; Ding, Ruoting

doi:10.1016/j.freeradbiomed.2021.03.037

Cited by 129 publications

(92 citation statements)

References 49 publications

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“…Quercetin has good curative effects on pharyngitis, and kaempferol and quercetagetin have anti-inflammatory effects. 38 , 39 Meanwhile, the network suggests that the components Honghua, Maidong, Jiegeng, Zhongjiefeng play a key role in the treatment of CP, which was confirmed by previous research. 11 Zhongjiefeng, bitter, is the commonly used medicine for the treatment of throat diseases; Maidong, slightly bitter and slightly cold, can moisturize lung and clear throat; Honghua can activate blood circulation and disperse blood stasis to relieve pain; Jiegeng can promote blood circulation and promote pharynx, detumescence, and pain relief.…”

Section: Discussionsupporting

confidence: 57%

Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment

Zhang

Yuan

et al. 2021

DDDT

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Purpose This study aimed to investigate the molecular mechanisms of compound herba Sarcandrae aerosol, also known as the Fufang Zhongjiefeng (FFZJF) aerosol, in treating chronic pharyngitis (CP) using network pharmacology and in vivo experimental approaches. Methods Active compounds and putative targets of five herbs in FFZJF were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction databases. The therapeutic targets of CP were obtained from OMIM, Durgbank, DisGeNT, and GAD databases. The active compounds-target networks were constructed using Cytoscape 3.6.1. The overlapping targets of FFZJF active compounds and CP targets were further analyzed using the String database to construct protein–protein interaction (PPI) network. KEGG pathway and Gene Ontology enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery. The predicted targets and pathways were validated in a group A β-hemolytic streptococcus-induced rat CP model. Results There were 45 active compounds identified from FFZJF and 11 potential protein targets identified for CP treatment. PPI network demonstrated that IL6, PTGS2, TLR-4, and TNF may serve as the key targets of FFZJF for the treatment of CP. The main functional pathways involving these key targets include cytokine secretion, inflammatory response, MyD88-dependent toll-like receptor signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. In a rat CP model, the elevation of serum TNF-α, IL1β, and IL6 levels, as well as the upregulation of TLR-4, MyD88, NF-κB P65 in the pharyngeal mucosal tissues could be effectively reduced by FFZJF treatment in a dose-dependent manner. Conclusion Through a network pharmacology approach and animal study, we predicted and validated the active compounds of FFZJF and their potential targets for CP treatment. The results suggest that FFZJF can markedly alleviate GAS-induced chronic pharyngitis by modulating the TLR-4/MyD88/NF-κB signaling pathways.

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Section: Discussionsupporting

confidence: 57%

Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment

Zhang

Yuan

et al. 2021

DDDT

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“…The antioxidant effects of some other polyphenols/phenolic compounds, including apocynin [268,269], baicalin [270,271], gastrodin [272], mangiferin [19], mulberrin [273], salvianolic acid [274,275], gallic acid [276,277], kaempferol [278], luteolin [279], naringenin [280], oleuropein [281,282], pycnogenol [283], silymarin [284], and protocatechuic acid [94], have been shown in Table 1. From the chemical point of view, Figure 2 presents the candidate chemical structures of neuroprotective polyphenols against SCI.…”

Section: Caffeic Acid Phenethylmentioning

confidence: 99%

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Fakhri

Abbaszadeh

Moradi

et al. 2022

Oxidative Medicine and Cellular Longevity

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Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross-linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant-derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post-SCI complications.

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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%

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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Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs–NF–κB signaling pathway and pyroptosis after secondary spinal cord injury

Cited by 129 publications

References 49 publications

Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment

Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

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

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