Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway

Li, Lin; Jiang, Weifeng; Yu, Baojian; Liang, Huiqi; Mao, Shihui; Hu, Xiaowei; Feng, Yan; Xu, Jiadong; Chu, Lisheng

doi:10.1016/j.biopha.2023.115653

Cited by 41 publications

(6 citation statements)

References 38 publications

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“…Icaritin, a phytoestrogen extracted from the dried stems and leaves of Epimedii , suppresses inflammatory responses and protects against cerebral ischemia–reperfusion injury via facilitating M2 microglial polarization and inhibiting M1 microglial polarization in a rat cerebral ischemia model (Yu et al 2022 ). Quercetin, a natural flavonoid exists in a variety of plants, ameliorates cerebral ischemia–reperfusion injury in a rat model of cerebral ischemia via inducing M2 microglial polarization (Li et al 2023d ). In our study, PPI treatment promoted M1 to M2 microglial phenotype shift in MCAO mice in vivo or after OGD/R in vitro, thus diminished neuroinflammation and promoted neuronal function recovery.…”

Section: Discussionmentioning

confidence: 99%

Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

Kang,

Sang,

Liu

et al. 2024

Mol Med

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Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia–reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen–glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia–reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia–reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

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Section: Discussionmentioning

confidence: 99%

Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

Kang,

Sang,

Liu

et al. 2024

Mol Med

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“…23 A recent report showed that intraperitoneal injection of quercetin can notably improve neurological function deficits following MCAO in rats. 24 Another study reported that quercetin can alleviated ischemic hypoxic brain damage in newborn mice. 25 Despite these findings, the effect of quercetin on GCI/R injury remains insufficiently explored.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, these findings from both in vitro and in vivo studies suggested that quercetin alleviated GCI/R injury by reducing the expression of proinflammatory cytokines and enhancing the expression of anti-inflammatory cytokines, aligning with the outcomes of previous research. 24 Activation of microglia and production of proinflammatory cytokines are features of neuroinflammation. 29 Microglia are rapidly activated during ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Quercetin Protects Against Global Cerebral ischemia‒reperfusion Injury by Inhibiting Microglial Activation and Polarization

Wang,

Li,

et al. 2024

JIR

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Background: This study aims to investigate the protective effect of quercetin against global cerebral ischemia-reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism. Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen-glucose deprivation/ reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF). Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1β and TNF-α. Conclusion:This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.

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Section: Antioxidant Bioactive Molecules Against Ischemic Strokementioning

confidence: 99%

“…Similarly, quercetin offers protective effects by inhibiting autophagy and acting as an antioxidant through HO-1 upregulation [70]. Furthermore, it facilitates microglia M2 polarisation by modulating the PI3K/Akt/NF-κB signalling pathway [70,71]. Similarly, quercetin offers protective effects by inhibiting autophagy and acting as an antioxidant through HO-1 upregulation [70].…”

Section: Polyphenolsmentioning

confidence: 99%

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

Briones-Valdivieso,

Briones,

Orellana-Urzúa

et al. 2024

Biomedicines

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Stroke is a major contributor to global mortality and disability. While reperfusion is essential for preventing neuronal death in the penumbra, it also triggers cerebral ischemia-reperfusion injury, a paradoxical injury primarily caused by oxidative stress, inflammation, and blood–brain barrier disruption. An oxidative burst inflicts marked cellular damage, ranging from alterations in mitochondrial function to lipid peroxidation and the activation of intricate signalling pathways that can even lead to cell death. Thus, given the pivotal role of oxidative stress in the mechanisms of cerebral ischemia-reperfusion injury, the reinforcement of the antioxidant defence system has been proposed as a protective approach. Although this strategy has proven to be successful in experimental models, its translation into clinical practice has yielded inconsistent results. However, it should be considered that the availability of numerous antioxidant molecules with a wide range of chemical properties can affect the extent of injury; several groups of antioxidant molecules, including polyphenols, carotenoids, and vitamins, among other antioxidant compounds, can mitigate this damage by intervening in multiple signalling pathways at various stages. Multiple clinical trials have previously been conducted to evaluate these properties using melatonin, acetyl-L-carnitine, chrysanthemum extract, edaravone dexborneol, saffron, coenzyme Q10, and oleoylethanolamide, among other treatments. Therefore, multi-antioxidant therapy emerges as a promising novel therapeutic option due to the potential synergistic effect provided by the simultaneous roles of the individual compounds.

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Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway

Cited by 41 publications

References 38 publications

Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

Quercetin Protects Against Global Cerebral ischemia‒reperfusion Injury by Inhibiting Microglial Activation and Polarization

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

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