Loureirin C ameliorates ischemia and reperfusion injury in rats by inhibiting the activation of the <scp>TLR4</scp>/<scp>NF‐κB</scp> pathway and promoting <scp>TLR4</scp> degradation

Xu, Jikai; Liu, Jingyu; Li, Qing; Mi, Yan; Zhou, Di; Wang, Jian; Chen, Gang; Liang, Dong; Li, Ning; Hou, Yue

doi:10.1002/ptr.7571

Cited by 9 publications

(4 citation statements)

References 50 publications

(60 reference statements)

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“…TLRs are an evolutionarily conserved family of receptors that play a key role in activating the innate immune system in response to microbial invasion [ 45 ]. After being stimulated by corresponding ligands, intracellular adapter proteins are recruited to TLRs to form signaling complexes and subsequently mediate downstream signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Oleuropein alleviates myocardial ischemia–reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway

He,

Huang,

Sun

et al. 2024

Chin Med

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Background Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth. Methods Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model. Results OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (KD = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo. Conclusion This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI.

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Section: Discussionmentioning

confidence: 99%

Oleuropein alleviates myocardial ischemia–reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway

He,

Huang,

Sun

et al. 2024

Chin Med

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“…Nrf2 is a crucial redox-sensitive transcription factor that responds to the translocation of the Keap1 homodimer from the cytoplasm to the nucleus [21]. In the nucleus, Nrf2 forms a dimer with the Maf protein, subsequently binding to antioxidant response elements in gene promoters and regulating the expression of antioxidant genes to protect cells from the pathological effects induced by oxidative stress [22]. Heme oxygenase (HO)-1 is a rate-limiting enzyme in heme degradation and is considered to be the most vital endogenous enzyme in preventing oxidative stress [23].…”

Section: Discussionmentioning

confidence: 99%

Tussilagone inhibits inflammation and oxidative stress to alleviate acute pancreatitis

2024

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Acute pancreatitis (AP) is a clinical emergency characterized by elevated levels of inflammation and oxidative stress, urging the need for the development of new and more efficacious treatments. Tussilagone (TSL), a compound from Tussilago farfara flower buds, is known to exhibit diverse properties, including anti-inflammatory activity, but its precise role in AP remains unclear. In this study, we investigated TSL’s impact on the progression of AP. To establish AP animal models, mice were intraperitoneally administered hyranolin. Our findings demonstrate that TSL effectively suppresses the progression of AP in these mice and decreases inflammation in their pancreatic tissues, as evidenced by reduced secretion of inflammatory cytokines such as interleukin (IL)-1β, Tumor necrosis factor (TNF)-α and IL-6 (p < 0.05). Notably, TSL also mitigates neutrophil infiltration into the pancreatic tissues of AP-afflicted mice and alleviates oxidative stress in AP mice, as confirmed by the measurements of Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) (p < 0.05). Remarkably, TSL exerts its inhibitory effects on inflammation and oxidative stress by blocking the nuclear factor (NF)-κB pathway and activating the NF-E2-related factor 2 (Nrf2) pathway. In conclusion, TSL can mitigate inflammation and oxidative stress, offering potential as a promising therapeutic agent for AP.

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“…Increased TLR4 expression is associated with a poor prognosis in mice with ischemic stroke [ 122 ]. According to a study using a rat model, inhibition of the TLR4/NF-κB pathway or promotion of TLR4 degradation could prevent microglia-induced neuroinflammation and alleviate post-ischemic stroke or reperfusion injury [ 123 ].…”

Section: Activation and Polarization Of Microglia Following Strokementioning

confidence: 99%

The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

2023

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Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage of pathological development. Neuroprotection is the main treatment in the acute phase, and functional recovery becomes primary in the subacute and chronic phases. Neuroplasticity is considered the basis of functional restoration and neurological rehabilitation after stroke, including the remodeling of dendrites and dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, and neurogenesis. Spatiotemporal development affects the spontaneous rewiring of neural circuits and brain networks. Microglia are resident immune cells in the brain that contribute to homeostasis under physiological conditions. Microglia are activated immediately after stroke, and phenotypic polarization changes and phagocytic function are crucial for regulating focal and global brain inflammation and neurological recovery. We have previously shown that the development of neuroplasticity is spatiotemporally consistent with microglial activation, suggesting that microglia may have a profound impact on neuroplasticity after stroke and may be a key therapeutic target for post-stroke rehabilitation. In this review, we explore the impact of neuroplasticity on post-stroke restoration as well as the functions and mechanisms of microglial activation, polarization, and phagocytosis. This is followed by a summary of microglia-targeted rehabilitative interventions that influence neuroplasticity and promote stroke recovery.

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Loureirin C ameliorates ischemia and reperfusion injury in rats by inhibiting the activation of the TLR4/NF‐κB pathway and promoting TLR4 degradation

Cited by 9 publications

References 50 publications

Oleuropein alleviates myocardial ischemia–reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway

Oleuropein alleviates myocardial ischemia–reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway

Tussilagone inhibits inflammation and oxidative stress to alleviate acute pancreatitis

The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

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