Suppressive Activities of Fisetin on Particulate Matter-induced Oxidative Stress

Sim, Hyunchae; Noh, Yeeun; Choo, Samyeol; Kim, Nayeon; Lee, Tae‐Ho; Bae, Jong‐Sup

doi:10.1007/s12257-021-0050-0

Cited by 24 publications

(7 citation statements)

References 35 publications

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“…To determine the release of HMGB1 in mouse sera or cell culture fluid, a competitive ELISA was conducted following previously described methods [ 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

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Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses

Park,

Heo,

Choi

et al. 2024

IJMS

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High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/β-catenin signaling pathway. However, no studies have yet determined the effects of CGK012 on sepsis. We investigated the potential of CGK012 to attenuate the excessive permeability induced by HMGB1 and enhance survival rates in a mouse model of sepsis with reduced HMGB1 levels following lipopolysaccharide (LPS) treatment. In both LPS-stimulated human endothelial cells and a mouse model exhibiting septic symptoms due to cecal ligation and puncture (CLP), we assessed proinflammatory protein levels and tissue damage biomarkers as indicators of reduced vascular permeability. CGK012 was applied after induction in human endothelial cells exposed to LPS and the CLP-induced mouse model of sepsis. CGK012 effectively mitigated excessive permeability and suppressed HMGB1 release, resulting in improved vascular stability, decreased mortality, and enhanced histological conditions in the mouse model of CLP-induced sepsis. In conclusion, our findings indicate that CGK012 treatment in mice with CLP-induced sepsis diminished HMGB1 release and increased the survival rate, suggesting its potential as a pharmaceutical intervention for sepsis.

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“…To determine the release of HMGB1 in mouse sera or cell culture fluid, a competitive ELISA was conducted following previously described methods [ 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

“…The viability of cultured HUVECs was estimated by performing the MTT assay after incubation with CGK012 for 48 h, as previously described [ 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses

Park,

Heo,

Choi

et al. 2024

IJMS

Self Cite

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“…MLMVECs were subjected to the treatment protocol described in earlier studies ( Sim et al ., 2021 ; Kim et al ., 2022a ). In brief, lung tissue was finely minced and subjected to a 45–60 min incubation at 37°C with collagenase A (1 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury

Cho,

Park,

Bae

2024

Biomol Ther (Seoul)

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Particulate matter (PM) constitutes a hazardous blend of organic and inorganic particles that poses health risks. Inhalation of fine airborne PM with a diameter of ≤ 2.5 μm (PM 2.5 ) can lead to significant lung impairments. (+)-afzelechin (AZC), a natural compound sourced from Bergenia ligulata, boasts a range of attributes, including antioxidant, antimicrobial, anticancer, and cardiovascular effects. However, knowledge about the therapeutic potential of AZC for patients with PM 2.5 -induced lung injuries remains limited. Thus, in this study, we investigated the protective attributes of AZC against lung damage caused by PM 2.5 exposure. AZC was administered to the mice 30 min after intratracheal instillation of PM 2.5 . Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were evaluated in mice exposed to PM 2.5 . Data demonstrated that AZC mitigated lung damage, reduced W/D weight ratio, and curbed hyperpermeability induced by PM 2.5 exposure. Furthermore, AZC effectively lowered plasma levels of inflammatory cytokines produced by PM 2.5 exposure. It reduced the total protein concentration in BALF and successfully alleviated PM 2.5 -induced lymphocytosis. Additionally, AZC substantially diminished the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1. In contrast, it elevated the protein phosphorylation of the mammalian target of rapamycin (mTOR). Consequently, the anti-inflammatory attribute of AZC positions it as a promising therapeutic agent for mitigating PM 2.5 -induced lung injuries by modulating the TLR4–MyD88 and mTOR–autophagy pathways.

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“…Mice from the LPS-induced septic shock model were euthanized and the left lobes of lungs were fixed in 10% neutral formalin for 24 h, followed by tissue processing and paraffin embedding. The paraffin blocks were sectioned into 2-μm thick sections and stained with H&E. Histopathological scoring was conducted by three experimental veterinary medicine experts using a random score index based on the degree of inflammatory cell infiltration and the extent of the injury area (0, normal; 1, mild; 3, moderate; 5, severe) with slight modifications from previous studies [ 33 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

Benzoylpaeoniflorin Activates Anti-Inflammatory Mechanisms to Mitigate Sepsis in Cell-Culture and Mouse Sepsis Models

Kim

Sim

Bae

2022

IJMS

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Xuebijing injection (XBJI) (comprising of five herbs) is a widely used traditional Chinese medicine for sepsis treatment. However, the bioactive components of XBJI and the mechanisms responsible for its sepsis-mitigating action have not been experimentally determined. One of the main bioactive compounds in XBJI—benzoylpaeoniflorin (BPF)—inhibits the expressions of key mediators of inflammation such as nuclear factor kappa B (NF-κB), cyclooxygenase-1 (COX-1), and COX-2. However, its effects on sepsis have not been determined yet. Therefore, here, we investigated the immunomodulatory effect of BPF on severely inflamed endothelial cells, THP-1 macrophages, peritoneal macrophages, and mice. Human umbilical vein endothelial cells (HUVECs) and THP-1-macrophages were activated using lipopolysaccharide (LPS) after pretreatment with BPF. Subsequently, changes in the expression profiles of pro-inflammatory molecules including inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined using quantitative real-time polymerase chain reaction (qPCR) and Western blot analysis. Furthermore, we monitored the phosphorylation of NF-kB and mitogen-activated protein kinases (MAPKs) to determine their activation levels. Using the LPS-induced mouse model of sepsis, we studied the effects of BPF on inflammatory cytokine production, pulmonary histopathology, and survival rates. Finally, we evaluated whether BPF protects against cecal ligation and puncture (CLP)-induced sepsis, as it closely mimics human sepsis. BPF pretreatment inhibited LPS-induced increase in mRNA and protein levels of iNOS, TNF-α, and IL-6 in HUVECs and THP-1-macrophages. It also suppressed LPS-mediated phosphorylation of p65, p38, JNK, and ERK. Mice with LPS-induced-sepsis who were treated with BPF had lower serum levels of IL-6, TNF-α, IL-1β, CXCL1, and CXCL2 than the control mice treated with BPF. Histopathology revealed that BPF treatment alleviated LPS-induced lung damage. In addition, in mice given a lethal dose of LPS, BPF treatment showed a dose-dependent improvement in survival rates. BPF treatment dose-dependently inhibited the LPS-induced IL-6, TNF-α, and CXCL1 production in peritoneal macrophages. BPF treatment also dose-dependently improved the survival rates in mice with CLP-induced sepsis. These results show that BPF alleviates LPS-stimulated septic conditions and protects mice from CLP-induced sepsis. Our research marks BPF as a potential drug in the treatment of sepsis and various inflammatory diseases.

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Suppressive Activities of Fisetin on Particulate Matter-induced Oxidative Stress

Cited by 24 publications

References 35 publications

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses

Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury

Benzoylpaeoniflorin Activates Anti-Inflammatory Mechanisms to Mitigate Sepsis in Cell-Culture and Mouse Sepsis Models

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