Harmine Alleviated Sepsis-Induced Cardiac Dysfunction by Modulating Macrophage Polarization via the STAT/MAPK/NF-κB Pathway DOI Creative Commons
Weibin Ruan, Xinyun Ji, Yating Qin

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 17, 2022

Sepsis is a dysregulated systemic inflammatory response that often leads to cardiac dysfunction, which termed sepsis-induced cardiomyopathy (SIC). Harmine, natural β-carboline alkaloid compound, has been shown exert pharmacological effects on several diseases. Here, we investigated whether harmine protected against SIC development and the underlying mechanisms. In vitro, expression of M1 phenotype markers iNOS COX-2 was increased in RAW 264.7 cells stimulated with lipopolysaccharide (LPS), but this effect reversed by intervention. Furthermore, LPS-induced increases levels cytokines, including IL-1β, IL-6, TNF-α, iNOS, COX-2, PGE2 TXB2, generated macrophages were suppressed when pretreated harmine. Meanwhile, our findings showed administration effectively attenuated inflammation apoptosis H9c2 proinflammatory environment produced macrophages, as evidenced reductions NLRP3 cleaved caspase 3 p-NF-κB/NF-κB ratio. The western blot results indicated mechanisms harmine-mediated inhibition polarization might be associated suppression STAT1/3, NF-κB MAPK activation. an LPS injection induced dysfunction decreased survival rate mice, alleviated treatment, relevant mechanism possibly attributed drug-induced attenuation apoptotic processes cardiomyocytes. Collectively, these implied treatment suppressing phenotypic macrophages.

Language: Английский

NLRP3 inflammasome-driven IL-1β and IL-18 contribute to lipopolysaccharide-induced septic cardiomyopathy DOI
Kenta Fujimura, Tadayoshi Karasawa, Takanori Komada

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2023, Volume and Issue: 180, P. 58 - 68

Published: May 11, 2023

Language: Английский

Citations

36
Autophagy in sarcopenia: Possible mechanisms and novel therapies DOI Open Access

Guangyang Xie,

Hongfu Jin, Herasimenka Mikhail

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115147 - 115147

Published: July 18, 2023

With global population aging, age-related diseases, especially sarcopenia, have attracted much attention in recent years. Characterized by low muscle strength, quantity or quality and physical performance, sarcopenia is one of the major factors associated with an increased risk falls disability. Much effort has been made to understand cellular biological physiological mechanisms underlying sarcopenia. Autophagy important self-protection mechanism that relies on lysosomes degrade misfolded proteins damaged organelles. Research designed obtain new insight into human diseases from autophagic aspect carried out progress, which encourages relevant studies relationship between autophagy plays a protective role modulating regenerative capability satellite cells, relieving oxidative stress suppressing inflammatory response. This review aims reveal specific interaction explore possible therapies hopes encouraging more research need unlocking novel promising ameliorate

Language: Английский

Citations

25
Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire DOI Creative Commons
Timur O. Yarovinsky,

Meiling Su,

Chaofei Chen

et al.

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101809 - 101809

Published: July 19, 2023

Language: Английский

Citations

24
Estradiol contributes to sex differences in resilience to sepsis-induced metabolic dysregulation and dysfunction in the heart via GPER-1-mediated PPARδ/NLRP3 signaling DOI
Joseph Adu‐Amankwaah, Adebayo Oluwafemi Adekunle, Ziqing Tang

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 156, P. 155934 - 155934

Published: May 16, 2024

Language: Английский

Citations

13
NLRP3 Inflammasome Targeting Offers a Novel Therapeutic Paradigm for Sepsis-Induced Myocardial Injury DOI Creative Commons

Yuzi Jin,

Joshua S. Fleishman,

Yudong Ma

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1025 - 1041

Published: Feb. 1, 2025

Cardiac or myocardial dysfunction induced by sepsis, known as sepsis-induced cardiomyopathy injury (SIMI), is a common complication of sepsis and associated with poor outcomes. However, the pathogenesis molecular mechanisms underlying SIMI remain poorly understood, requiring further investigations. Emerging evidence has shown that NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasomes contribute to SIMI. Compounds inhibit NLRP3-associated pyroptosis may exert therapeutic effects against In this review, we first outlined principal elements NLRP3 signaling cascade summarized recent studies highlighting how activation contributes We selective small-molecule modulators function inhibitors delineated their action attenuate Finally, discuss major limitations current paradigm propose possible strategies overcome them. This review highlights pharmacological inhibition promising strategy.

Language: Английский

Citations

1
Integrated Omics Insights into Dapagliflozin Effects in Sepsis-Induced Cardiomyopathy DOI Creative Commons

Weiwei Lai,

Li Liu, Shuhang Wang

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 286 - 286

Published: Feb. 14, 2025

Sepsis-induced cardiomyopathy (SIC) is a life-threatening cardiac complication of sepsis with limited therapeutic options. Dapagliflozin, sodium-glucose cotransporter 2 (SGLT2) inhibitor, has demonstrated cardioprotective effects in heart failure, but its role mitigating sepsis-related dysfunction remains unclear. A retrospective cohort analysis was conducted to assess the impact pre-hospital dapagliflozin use on major adverse cardiovascular events (MACEs) and survival patients SIC. Additionally, murine SIC model established using cecal ligation puncture (CLP) evaluate function, histopathology, biomarkers myocardial injury. Transcriptomic metabolomic profiling, combined multi-omics integration, employed elucidate molecular mechanisms underlying dapagliflozin's effects. In clinical cohort, associated significant reduction risk MACE improved outcomes. model, restored reduced injury, alleviated histological damage. Multi-omics revealed that modulates inflammatory responses, enhances autophagy, regulates metabolic pathways such as AMPK signaling lipid metabolism. Key regulatory genes metabolites were identified, providing mechanistic insights into actions dapagliflozin. Dapagliflozin significantly improves outcomes sepsis-induced through multi-level regulation inflammation, energy metabolism, cellular pathways. These findings establish promising strategy for SIC, offering translational treatment dysfunction.

Language: Английский

Citations

1
An Integrated Network Pharmacology and RNA-seq Approach for Exploring the Protective Effect of Isoquercitrin in Doxorubicin-Induced Cardiotoxicity: Identification of Novel Genes DOI
Habib Alam,

Wei Bailing,

Feng Zhao

et al.

Cardiovascular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Language: Английский

Citations

1
Verbascoside protects from LPS-induced septic cardiomyopathy via alleviating cardiac inflammation, oxidative stress and regulating mitochondrial dynamics DOI Creative Commons
Xuanfeng Zhu, Min Sun, Hongmei Guo

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2022, Volume and Issue: 233, P. 113327 - 113327

Published: Feb. 21, 2022

Verbascoside (VB), as an active component of multiple medicinal plants, has been proved to exert anti-oxidative, anti-aging and neuroprotective effects. This study was designed investigate whether VB could play a cardioprotective role in septic heart injury.Mice were injected with lipopolysaccharide (LPS; 10 mg/kg) induce sepsis. The treatment group received intraperitoneally injection (20 before LPS challenge. Transthoracic echocardiography, ELISA, immunofluorescence, qPCR performed assess the effect on function, oxidative stress, inflammation apoptosis. Transmission electronic microscopy immunoblotting used evaluate mitochondrial morphology biogenesis heart. In vitro experiments also repeat above-mentioned assays.Compared group, showed improved cardiac function alleviated stress inflammatory cell infiltration, well cardiomyocyte Specifically, restore sepsis-induced alterations via regulating biogenesis. These results confirmed experiments.Verbascoside protected from cardiomyopathy by inhibiting inflammation, apoptosis, promoting

Language: Английский

Citations

34
Emerging Roles of Inflammasomes in Cardiovascular Diseases DOI Creative Commons
Yingnan Liao, Kui Liu, Liyuan Zhu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

Cardiovascular diseases are known as the leading cause of morbidity and mortality worldwide. As an innate immune signaling complex, inflammasomes can be activated by various cardiovascular risk factors regulate activation caspase-1 production secretion proinflammatory cytokines such IL-1β IL-18. Accumulating evidence supports that play a pivotal role in progression atherosclerosis, myocardial infarction, heart failure. The best-known NLRP1, NLRP3, NLRC4, AIM2 inflammasomes, among which NLRP3 inflammasome is most widely studied response disease development. This review focuses on regulation mechanism diseases, research progress targeting for related intervention.

Language: Английский

Citations

33
Malvidin alleviates mitochondrial dysfunction and ROS accumulation through activating AMPK-α/UCP2 axis, thereby resisting inflammation and apoptosis in SAE mice DOI Creative Commons
Panpan Zhao, Xiaomin Li,

Qiankun Yang

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 9, 2023

This study aimed to explore the protective roles of malvidin in life-threatened sepsis-associated encephalopathy (SAE) and illustrate underlying mechanism. SAE mice models were developed treated with for subsequently effects evaluation. Malvidin restored neurobehavioral retardation, declined serum S100β NSE levels, sustained cerebrum morphological structure, improved blood-brain barrier integrity elevated tight junction proteins, decreased evans blue leakage, finally protect from brain injury. Mechanistically, prevented mitochondrial dysfunction enhanced JC-1 aggregates ATP ROS accumulation lipid peroxidation increased antioxidant enzymes. UCP2 protein levels found be after LPS stimulation BV-2 cells, recovered its a dependent manner. In vivo inhibition genipin or vitro interference siRNA both disrupted membrane potential, intensified DCF signals, being key target malvidin. Moreover, dorsomorphin block assays verified that upregulated expression through phosphorylating AMPK models. Also, alleviated progression ROS-dependent NLRP3 inflammasome activation mediated pro-inflammatory cytokines secretion pathway apoptosis weakened body formation tunel positive Bax, cytochrome C, caspase-3 Bcl-2 levels. Overall, this illustrated targeted AMPK-α/UCP2 axis restore LPS-induced alleviate accumulation, which further inhibits way, ultimately protected mice, providing reference development prophylactic approach.

Language: Английский

Citations

23