Effects of breviscapine on cerebral ischemia-reperfusion injury and intestinal flora imbalance by regulating the TLR4/MyD88/NF-κB signaling pathway in rats

Chen, Haidong; Jiang, Ming-Zhao; Zhao, Yingying; Li, Xin; Lü, Hai; Yang, Wan-Qi; Lai, Yuanming

doi:10.1016/j.jep.2022.115691

Cited by 12 publications

(15 citation statements)

References 35 publications

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“…Recent studies have revealed the protective effects of Bre against renal injury ( Liu et al, 2016b ), cerebral ischaemia‒reperfusion injury ( Chen et al, 2022 ), liver injury ( Lan et al, 2022 ; Liu et al, 2018 ), and myocardial damage ( Wang et al, 2009 ) through various mechanisms, such as inflammation, ROS production, and endoplasmic reticulum stress ( Schena & Gesualdo, 2005 ; Wolf, 2004 ). Although inflammation is a protective response to infection and tissue injury, an excessive inflammatory response results in long-lasting tissue injury ( Liu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Breviscapine alleviates podocyte injury by inhibiting NF-κB/NLRP3-mediated pyroptosis in diabetic nephropathy

Sun¹,

Ding²,

Chen³

et al. 2023

PeerJ

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Podocyte injury is a critical factor in the pathogenesis of diabeticnephropathy (DN). Emerging evidence has demonstrated that breviscapine (Bre) exerts a renoprotective effect on diabetic rats. However, the effects of Bre on regulating podocyte injury under high glucose (HG) conditions remain unclear. In this study, an experimental mouse model of DN was induced by intraperitoneal injections of streptozotocin (STZ) in vivo. The effects of Bre on podocyte injury were assessed using cell counting kit-8 (CCK-8) assay, TdT-mediated dUTPnick-endlabelling (TUNEL) staining, quantitative real-time PCR (qRT‒PCR) and western blot analysis. We found that renal function was significantly decreased in diabetic mice, and this effect was blocked by Bre treatment. Bre effectively increased podocyte viability and inhibited HG-induced cell apoptosis. Furthermore, Bre ameliorated HG-induced podocyte injury, as evidenced by decreased α-smooth muscle actin (α-SMA) expression and increased podocin and synaptopodin expression. Mechanistically, Bre inhibited HG-induced nuclear factorkappaB (NF-κB) signalling activation and subsequently decreased NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, resulting in a decrease in pyroptosis. Pharmacological inhibition of NLRP3 decreased HG-induced podocyte injury, whereas the NLRP3 agonist abrogated the effects of Bre on inhibiting podocyte injury. In summary, these results demonstrate that Bre alleviates HG-induced podocyte injury and improves renal function in diabetic mice, at least in part by inhibiting NF-κB/NLRP3-mediated pyroptosis.

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Section: Discussionmentioning

confidence: 99%

Breviscapine alleviates podocyte injury by inhibiting NF-κB/NLRP3-mediated pyroptosis in diabetic nephropathy

Sun¹,

Ding²,

Chen³

et al. 2023

PeerJ

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“…When LPS and peptidoglycan bind the toll-like receptor (TLR2, TLR4) on the cell membrane, the receptor signals to the IRAK kinase, which activates the NF-kB1 transcription factor leading to the increased secretion of pro-inflammatory cytokines, such as IL6 [ 7 , 8 ]. This TLR pathway can be targeted by drugs, such as IRAK-1 kinase and NF-kB1 inhibitors or IL-6 blocking antibodies, to reduce cancer progression [ 7 , 8 , 41 ]. Recent studies suggest that an improved understanding of the mechanism and causal relationship between bacteria and cancer cells can be harnessed to develop new therapeutic strategies against cancer [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device

Mittal

Cupp

Kang

2023

Sensors

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The imbalance in the gut microbiome plays a vital role in the progression of many diseases, including cancer, due to increased inflammation in the body. Since gut microbiome-induced inflammation can serve as a novel therapeutic strategy, there is an increasing need to identify novel approaches to investigate the effect of inflammation instigated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow testing of the causal relationship of the microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to investigate the effects of bacteria and inflammatory stress on cancer cells in vitro. To test the microfluidic chip, we used colorectal cancer cells, as an increased microbiome abundance has been associated with poor outcomes in colorectal cancer. We cultured colorectal cancer cells with Bacillus bacteria or lipopolysaccharide (LPS), a purified bacterial membrane that induces a significant inflammatory response, in the microfluidic device. Our results showed that both LPS and Bacillus significantly accelerated the growth of colorectal cancer cells, therefore supporting that the increased presence of certain bacteria promotes cancer cell growth. The microfluidic device included in this study may have significant implications in identifying new treatments for various cancer types in the future.

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“…Unfortunately, there is currently a lack of specific treatment options ( Qin et al, 2022 ). The TLR/MyD88/NF-κB signaling pathway has been found to be involved in the development of neuroinflammation injury in CIRI ( Mitsios et al, 2006 ; Chen et al, 2022 ). MyD88 is a core transduction protein involved in this signaling pathway ( Kawai and Akira, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

TJ-M2010-5, a novel CNS drug candidate, attenuates acute cerebral ischemia-reperfusion injury through the MyD88/NF-κB and ERK pathway

Zhao

Zhang

et al. 2022

Front. Pharmacol.

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Background: Cerebral ischemia-reperfusion injury (CIRI) inevitably occurs after vascular recanalization treatment for ischemic stroke. The accompanying inflammatory cascades have a major impact on outcome and regeneration after ischemic stroke. Evidences have demonstrated that TLR/MyD88/NF-κB signaling contributes to CIRI. This study aimed to investigate the druggability of MyD88 in the central nervous system (CNS) and the neuroprotective and anti-neuroinflammatory effects of the MyD88 inhibitor TJ-M2010-5 on CIRI.Methods: A middle cerebral artery occlusion (MCAO) model was used to simulate CIRI in mice. BV-2 cells were stimulated with oxygen glucose deprivation/reoxygenation (OGD/R) or lipopolysaccharide, and SH-SY5Y cells were induced by OGD/R in vitro. Neurological deficit scores and cerebral infarction volumes were evaluated. Immunofluorescence staining was performed to measure neuronal damage and apoptosis in the brain. The anti-neuroinflammatory effect of TJ-M2010-5 was evaluated by analyzing the expression of inflammatory cytokines, activation of microglia, and infiltration of peripheral myeloid cells. The expression of proteins of the MyD88/NF-κB and ERK pathway was detected by Simple Western. The concentrations of TJ-M2010-5 in the blood and brain were analyzed by liquid chromatography-mass spectrometry.Results: The cerebral infarction volume decreased in mice treated with TJ-M2010-5, with the most prominent decrease being approximately 80% of the original infarction volume. Neuronal loss and apoptosis were reduced following TJ-M2010-5 treatment. TJ-M2010-5 inhibited the infiltration of peripheral myeloid cells and the activation of microglia. TJ-M2010-5 also downregulated the expression of inflammatory cytokines and inhibited the MyD88/NF-κB and ERK pathway. Furthermore, TJ-M2010-5 showed good blood-brain barrier permeability and no neurotoxicity.Conclusion: TJ-M2010-5 has an excellent therapeutic effect on CIRI as a novel CNS drug candidate by inhibiting excessive neuroinflammatory responses.

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Effects of breviscapine on cerebral ischemia-reperfusion injury and intestinal flora imbalance by regulating the TLR4/MyD88/NF-κB signaling pathway in rats

Cited by 12 publications

References 35 publications

Breviscapine alleviates podocyte injury by inhibiting NF-κB/NLRP3-mediated pyroptosis in diabetic nephropathy

Breviscapine alleviates podocyte injury by inhibiting NF-κB/NLRP3-mediated pyroptosis in diabetic nephropathy

Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device

TJ-M2010-5, a novel CNS drug candidate, attenuates acute cerebral ischemia-reperfusion injury through the MyD88/NF-κB and ERK pathway

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