Sepsis is a life-threatening condition characterized by multiple organ dysfunction syndrome resulted from dysregulated host responses to infection. Sepsis-associated encephalopathy (SAE) is one of the most common symptoms of acute-phase sepsis, with nearly 70 % of patients with sepsis ultimately developing SAE. Pyroptosis represents a type of cell death that is initiated by inflammation. This cell death type is associated with various infectious and noninfectious diseases. The gasdermin family proteins are crucial cell death executors and critical components in regulating the canonical pyroptosis pathway in microglia. In this review, we summarize the inhibitory effects of several drugs and genes on the pyroptosis pathway. Our findings suggest that several drugs (puerarin, VX765, HC067047, dexpramipexole, and Danhong injection), erbin gene, and TRIM45 knockdown improve SAE by suppressing the canonical pathway of NLRP3/caspase-1/gasdermin D-mediated pyroptosis. Therefore, they have significant importance in terms of brain protection. Moreover, we review the relevant literature published in recent years and summarize the research status and development prospects in this field to provide a basis for subsequent related research.

Diabetic stroke-associated acute intestinal injury is characterized by high mortality, disability, and poor prognosis due to the lack of effective therapies. Our prior research demonstrated that administration of 300 mg/kg sodium butyrate (NaB) can improve neurological outcomes post-diabetic stroke. Nonetheless, whether the effect of NaB is related to intestinal regulation, along with its underlying mechanisms, remains uncertain. This study aims to investigate the effects and mechanistic pathways of NaB on diabetic stroke-associated acute intestinal injury. A middle cerebral artery occlusion/reperfusion model was established in mice with streptozotocin-induced diabetes. The results demonstrated that NaB alleviated colonic injury 24 h after reperfusion in diabetic stroke. Pyroptosis-related protein levels in colonic tissues were significantly elevated following diabetic stroke but were markedly reduced with NaB treatment. NaB also improved gut barrier integrity and reduced inflammation, promoting epithelial barrier self-repair. In the NaB combined with lipopolysaccharide group, lipopolysaccharide administration induced a significant inflammatory response in the colonic tissue. Conversely, treatment with NaB and VX-765 (an inhibitor for Caspase-1) led to a notable alleviation in intestinal inflammation. These findings suggest that NaB mitigates colonic injury and enhances barrier function following diabetic stroke, potentially through the Caspase-1/Gasdermin D pyroptosis pathway. This study may provide a novel strategy and direction for intestinal rehabilitation in diabetic stroke patients.

Depression is a prevalent and debilitating condition that has a severe negative impact on a person's life. Chronic stress exposure plays a substantial role in the development of depression. In the present study, rats were exposed to chronic unpredictable mild stress (CUMS) for four weeks. Empagliflozin (EMPA), a Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitor, is an oral antidiabetic agent exhibiting antioxidant, anti-inflammatory, and antiapoptotic effects. This study aimed to examine the antidepressant effect of EMPA in an experimental animal model of depression induced by CUMS in rats and explore the probable underlying mechanisms. Rats were treated with EMPA, per-orally, at a dose of 10 mg/kg/day for four weeks. EMPA treatment counteracted CUMS-induced histopathological, biochemical and behavioral alterations. EMPA suppressed the CUMS-induced increase in the oxidative stress, inflammatory, and apoptotic markers, where levels of MDA, IL-1β, TNF-α, NF-κB, NLRP3 and active caspase 3 were reduced by 29.6 %, 24.8 %, 17.9 %, 36.6 %, 24.5 % and 41.5 %, respectively, compared to the disease group. Furthermore, EMPA decreased the level of the microglial activation marker, iba-1 by 24 % in comparison to the disease group. In addition, EMPA treatment decreased blood glucose levels by 39 %, decreased serum insulin levels by 60.6 %, decreased HOMA-IR by 76.5 % and increased GLUT 4 expression, compared to the CUMS group, all which proves that EMPA has an effect insulin signaling and alleviates insulin resistance. Our results conclude that modulating key factors involved in depression, such as inflammation, oxidative stress, and NLRP3 inflammasome pathway, accounts for the anti-depressant effect of EMPA.

Neferine is a bisbenzylisoquinoline alkaloid derived from the seed embryo of Nelumbo nucifera, a traditional Chinese medicine. It has been extensively studied for its therapeutic potential in various disease models. Extensive research has highlighted its diverse pharmacological activities, including antitumor, anti‑inflammatory, anti‑fibrosis, anti‑oxidative stress, anti‑platelet aggregation and anti‑arrhythmic effects. The present review, however, focuses on the anti‑inflammatory properties of neferine, emphasizing its fundamental mechanisms as demonstrated in both in vivo and in vitro studies. By critically evaluating its effect on inflammation and the underlying pathways, this review aims to provide a comprehensive understanding of the potential of neferine in the management of inflammatory diseases. Furthermore, it seeks to establish a foundational framework for the future development of neferine as a novel therapeutic agent for inflammatory conditions.

Cataract remains a major cause of ocular blindness. Cyclic Arg-Gly-Asp-d-Phe-Lys (RGD) peptide was introduced to the surface of self-assembled hybrid micelles for the co-delivery of poly (ADP-ribose) polymerase 1 (PARP-1) small-interfering RNA (siRNA) and quercetin (Q/siP-c-M). Q/siP-c-M exhibited uniform particle size distribution, good dispersibility, high encapsulation efficiency, and strong stability for siRNA and quercetin. Q/siP-c-M significantly improved the transcorneal co-delivery of siRNA and quercetin to the deeper cornea and led to greater drug accumulation. In addition, Q/siP-c-M significantly increased the activity of catalase and the content of adenosine triphosphate (ATP), reduced the expression of PARP-1 protein, and effectively prevented lipid peroxidation in the lens. Among selenite-induced cataract rats, the Q/siP-c-M-treated rats produced higher levels of ATP and catalase, as well as lower levels of malondialdehyde and PARP-1 protein expression compared with those in the model group. Administration of quercetin further resulted in a decrease in neutrophil extracellular trap formation and downregulation of gene expression of related proteins and pro-inflammatory cytokines. These observations indicated that quercetin has the potential to serve as a therapeutic for alleviating an excessive inflammatory reaction characterized by an overabundance of neutrophil extracellular traps in the eyes. Therefore, this study highlights the potential of Q/siP-c-M against cataract development through the regulation of the immune response by regulating inflammatory conditions. Furthermore, Q/siP-c-M may offer benefits in terms of apoptosis attenuation for lens epithelial cells.

Natural products are an important source of drug candidates against fatty liver. Herein, two previously undescribed monocyclic polyprenylated acylphloroglucinols (MPAPs, 1 and 2) and three new polycyclic polyprenylated acylphloroglucinols (PPAPs, 3-5) were isolated from the pericarps of Garcinia multiflora, and structurally elucidated by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) calculations, together with five known PPAPs. Compounds 1 and 2 are rare dinor-MPAPs. In lipopolysaccharide (LPS)-induced RAW264.7 macrophages, compounds 1, 3 and 4 significantly suppressed nitric oxide production. Among them, compound 3 showed the best inhibitory effect with an IC50 value of 4.12 ± 0.94 μМ. Furthermore, compound 3 effectively reduced interleukin-1β secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. Interestingly, the conditioned medium from LPS plus nigericin-stimulated THP-1 macrophages pre-treated with compound 3 attenuated lipid accumulation in oleic acid plus palmitic acid (2/1)-induced HepG2 hepatocytes. Taken together, these findings expand the chemical diversity of G. multiflora, and further demonstrate the potential of PPAPs as candidates for treating steatohepatitis.

Herein, we designed and synthesized a series of novel bis-amide small molecule anti-inflammatory agents, among them, compound ST12 showed most potent anti-inflammatory activity. ST12 effectively inhibited the production of nitric oxide (NO) (inhibition rate of 52.67 ± 0.03 % at 10 μM) and downregulated the mRNA levels of proinflammatory cytokines iNOS, IL-6, IL-1β and TNF-α in lipopolysaccharide (LPS) induced RAW264.7 cells. Furthermore, mechanism studies suggest that compound ST12 exerted anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome. Importantly, ST12 effectively ameliorated DSS-induced colitis in vivo. Taken together, ST12 is worthy of further investigation as a small molecule anti-inflammatory agent for treatment of inflammatory bowel diseases (IBD).

Sevoflurane anesthesia is frequently linked to cognitive dysfunction in elderly individuals, with neuroinflammation, particularly microglial activation, playing a critical role in this pathology. Although the potassium channel Kv1.3 has been shown to regulate microglial activation, its involvement in sevoflurane-induced cognitive dysfunction remains poorly understood. In this study, cognitive dysfunction was induced in 17-month-old C57BL/6J mice by exposing them to 3 % sevoflurane for 5 h. Kv1.3 expression and cellular distribution were analyzed using RT-qPCR, Western blot, and immunofluorescence. To investigate the mechanisms underlying this process, mice were pretreated with the selective Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1) or the NLRP3 inflammasome inhibitor MCC950 prior to sevoflurane exposure. Behavioral tests, hematoxylin-eosin (H&E) staining, nissl staining, immunohistochemistry, immunofluorescence, Western blot and enzyme-linked immunosorbent assay (ELISA) were performed for further assessment. Sevoflurane exposure led to a significant increase in Kv1.3 expression, which was strongly correlated with cognitive impairments and neuronal damage. Pharmacological inhibition of Kv1.3 with PAP-1 alleviated learning and memory deficits, reduced neuronal damage, and inhibited microglial activation. PAP-1 treatment also promoted the transition of microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype and suppressed NLRP3 inflammasome activation. Furthermore, the NLRP3 inflammasome inhibitor MCC950 also reduced microglial activation and phenotypic shift following sevoflurane exposure. These results suggest that Kv1.3 channel play a critical role in sevoflurane-induced cognitive dysfunction in aged mice through NLRP3-dependent microglial modulation. Targeting Kv1.3 could provide a potential therapeutic strategy for alleviating postoperative cognitive dysfunction associated with sevoflurane anesthesia.

Mitochondria are traditionally known as the cells' powerhouses; however, their roles go far beyond energy suppliers. They are involved in intracellular signaling and thus play a crucial role in shaping cells' destiny and functionality, including immune cells. Mitochondria can be actively exchanged between immune and non-immune cells via mechanisms such as nanotubes and extracellular vesicles. The mitochondria transfer from immune cells to different cells is associated with physiological and pathological processes, including inflammatory disorders, cardiovascular diseases, diabetes, and cancer. On the other hand, mitochondrial transfer from mesenchymal stem cells, bone marrow-derived stem cells, and adipocytes to immune cells significantly affects their functions. Mitochondrial transfer can prevent exhaustion/senescence in immune cells through intracellular signaling pathways and metabolic reprogramming. Thus, it is emerging as a promising therapeutic strategy for immune system diseases, especially those involving inflammation and autoimmune components. Transferring healthy mitochondria into damaged or dysfunctional cells can restore mitochondrial function, which is crucial for cellular energy production, immune regulation, and inflammation control. Also, mitochondrial transfer may enhance the potential of current therapeutic immune cell-based therapies such as CAR-T cell therapy.

Urolithin A (UA), a metabolite of natural polyphenols produced by the gut microbiota, alleviates the symptoms of rheumatoid arthritis (RA) by inhibiting the inflammatory response. UA alleviates the clinical symptoms of RA by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. In this study, we established a CIA model in 8-week-old DBA mice and chose LPS-stimulated NIH/3 T3 cells to explore the effects of UA and attempted to elucidate its potential mechanisms. Our results showed UA significantly reduced arthritis scores, and inhibited inflammation, pannus formation, and cartilage and bone destruction of inflamed joints in CIA mice. In vitro, UA inhibited LPS-induced migration and proliferation, and alleviated NLRP3-mediated pyroptosis, significantly inhibiting the protein expression levels of NLRP3, N-terminal gasdermin D, interleukin-1β, caspase-1, and ASC in NIH/3T3 cells. A mechanistic investigation revealed that LPS enhanced phosphorylation of NF-κB and downregulated that of AMPK, which were categorically counteracted by UA treatment. Therefore, UA represents a new class of promising RA treatments targeting fibroblasts, widening the therapeutic options for RA.

Drug-induced toxicity is an important issue in clinical medicine, which typically results in organ dysfunction and adverse health consequences. The family of NOD-like receptors (NLRs) includes intracellular proteins involved in recognizing pathogens and triggering innate immune responses, including the activation of the NLRP3 inflammasome. The NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3) inflammasome is a critical component for both innate and adaptive immune responses and has been implicated in various drug-induced toxicities, including hepatic, renal, and cardiovascular diseases. The unusual activation of the NLRP3 inflammasome causes the release of pro-inflammatory cytokines, such as IL-1β and IL-18, which can lead to more damage to tissues. Targeting NLRP3 inflammasome is a potential therapeutic endeavour for suppressing drug-induced toxicity. This review provides insights into the mechanism, drug-induced organ toxicity, therapeutic strategies, and prospective therapeutic approaches of the NLRP3 inflammasome and summarizes the developing therapies that target the inflammasome unit. This review has taken up one of the foremost endeavours in understanding and inhibiting the NLRP3 inflammasome as a means of generating safer pharmacological therapies.

Huazhuo Sanjie Chubi Decoction (HSCD), a Chinese herbal formula, is traditionally used for the treatment of spleen deficiency with dampness accumulation and is commonly used to treat gouty arthritis (GA). However, the potential active compounds and mechanisms of HSCD remain unclear.

To elucidate the key bioactive compounds and pharmacological mechanisms of HSCD in treating GA.

The chemical compounds in HSCD were qualitatively and quantitatively analyzed using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Network pharmacology and molecular docking were employed to identify key active compounds and associated molecular pathways. Monosodium urate (MSU)-induced RAW264.7 macrophages and GA rat model were used to explore the potential therapeutic effects and mechanisms of HSCD in treating GA.

UPLC-MS/MS identified 184 compounds in HSCD, with 28 key compounds quantified. Network pharmacology revealed that verbenalin, limonin, and quercitrin are strongly associated with the molecular mechanisms of HSCD in treating GA via the PI3K-AKT signaling pathway. These compounds exhibited strong binding affinity to PI3K and AKT proteins. In RAW264.7 cells, HSCD and the three identified compounds dose-dependently reduced inflammation by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). They also downregulated both the PI3K-AKT and apoptosis signaling pathways. In rats, HSCD exerted therapeutic effects against acute GA by alleviating swelling and pathological damage to the ankle joints. Moreover, the molecular mechanisms in vivo were confirmed to be associated with the PI3K-AKT and apoptosis signaling pathways.

This study employed a multivariant approach to demonstrate the main bioactive compounds and molecular mechanisms of HSCD in treating GA, thereby supporting its traditional use.

Astrocytes play a pivotal role in the inflammatory response triggered by traumatic brain injury (TBI). They are not only involved in the initial inflammatory response following injury but also significantly contribute to Astrocyte activation and inflammasome release are key processes in the pathophysiology of TBI, significantly affecting the progression of secondary injury and long-term outcomes. This comprehensive review explores the complex triggering mechanisms of astrocyte activation following TBI, the intricate pathways controlling the release of inflammasomes from activated astrocytes, and the subsequent neuroinflammatory cascade and its multifaceted roles after injury. The exploration of these processes not only deepens our understanding of the neuroinflammatory cascade but also highlights the potential of astrocytes as critical therapeutic targets for TBI interventions. We then evaluate cutting-edge research aimed at targeted therapeutic approaches to modulate pro-inflammatory astrocytes and discuss emerging pharmacological interventions and their efficacy in preclinical models. Given that there has yet to be a relevant review elucidating the specific intracellular mechanisms targeting astrocyte release of inflammatory substances, this review aims to provide a nuanced understanding of astrocyte-mediated neuroinflammation in TBI and elucidate promising avenues for therapeutic interventions that could fundamentally change TBI management and improve patient outcomes. The development of secondary brain injury and long-term neurological sequelae. By releasing a variety of cytokines and chemokines, astrocytes regulate neuroinflammation, thereby influencing the survival and function of surrounding cells. In recent years, researchers have concentrated their efforts on elucidating the signaling crosstalk between astrocytes and other cells under various conditions, while exploring potential therapeutic interventions targeting these cells. This paper highlights the specific mechanisms by which astrocytes produce inflammatory mediators during the acute phase post-TBI, including their roles in inflammatory signaling, blood-brain barrier integrity, and neuronal protection. Additionally, we discuss current preclinical and clinical intervention strategies targeting astrocytes and their potential to mitigate neurological damage and enhance recovery following TBI. Finally, we explore the feasibility of pharmacologically assessing astrocyte activity post-TBI as a biomarker for predicting acute-phase neuroinflammatory changes.

The NLRP3 inflammasome plays a pivotal role in the pathogenesis of acute lung injury (ALI) by regulating pyroptosis, a highly inflammatory form of programmed cell death. NLRP3-mediated pyroptosis leads to alveolar epithelial cell injury, increased pulmonary microvascular endothelial permeability, excessive alveolar macrophage activation, and neutrophil dysfunction, collectively driving ALI progression. In addition to the classical NLRP3-dependent pathway, the non-canonical pyroptosis pathway (caspase-4/5/11) also contributes to ALI by inducing pyroptotic cell death in AECs and ECs, further amplifying NLRP3 activation through damage-associated molecular patterns (DAMP) release. Moreover, neutrophils (NE) pyroptosis exhibits dual roles in ALI, as it enhances pathogen clearance but also exacerbates excessive inflammation and tissue damage, highlighting the complexity of its regulation. Targeting the NLRP3 inflammasome and pyroptotic pathways has emerged as a promising therapeutic strategy for ALI. Various NLRP3 inhibitors (e.g., MCC950, CY-09, OLT1177) and pyroptosis inhibitors have demonstrated significant anti-inflammatory and tissue-protective effects in preclinical models. However, the clinical translation of NLRP3-targeted therapies remains challenging due to off-target effects, potential immunosuppression, lack of patient stratification strategies, and compensatory activation of alternative inflammasomes (e.g., AIM2, NLRC4). Future studies should focus on optimizing the selectivity of NLRP3 inhibitors, developing personalized therapeutic approaches, and exploring combination strategies to enhance their clinical applicability in ALI.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.

Despite mounting evidence linking circular RNAs (circRNAs) to various diseases, their specific role in liver damage triggered by obstructive sleep apnea (OSA) remains ambiguous. This study investigates alterations in circRNA expression patterns in a mouse model subjected to chronic intermittent hypoxia (CIH), aiming to elucidate the pathways that lead to liver damage associated with OSA. We established the CIH model and conducted circRNA microarray analysis on liver samples from both CIH and control groups. The findings were substantiated via qRT-PCR. Furthermore, a comprehensive circRNA-miRNA-mRNA (ceRNA) network was developed, followed by the analysis of GO and KEGG pathways to further elucidate the underlying biological processes. We identified 259 differentially expressed circRNAs, comprising 86 that were upregulated and 173 that were downregulated in CIH mice. The ceRNA analysis suggested that these circRNAs may modulate gene expression by sequestering miRNAs. Our findings highlight potential therapeutic targets for liver pathologies associated with OSA.

Pyroptosis is a distinct form of programmed cell death characterized by the rupture of the cell membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects the tumor microenvironment and antitumor immunity by releasing damage-associated molecular patterns (DAMPs) and pro-inflammatory mediators, thereby establishing it as a pivotal target in cancer immunotherapy. This review thoroughly explores the molecular mechanisms underlying pyroptosis, with a particular focus on inflammasome activation and the gasdermin family of proteins (GSDMs). It examines the role of pyroptotic cell death in reshaping the tumor immune microenvironment (TIME) involving both tumor and immune cells, and discusses recent advancements in targeting pyroptotic pathways through therapeutic strategies such as small molecule modulators, engineered nanocarriers, and combinatory treatments with immune checkpoint inhibitors. We also review recent advances and future directions in targeting pyroptosis to enhance tumor immunotherapy with immune checkpoint inhibitors, adoptive cell therapy, and tumor vaccines. This study suggested that targeting pyroptosis offers a promising avenue to amplify antitumor immune responses and surmount resistance to existing immunotherapies, potentially leading to more efficacious cancer treatments.

Vascular dementia, the second most common type of dementia globally after Alzheimer's disease, is associated with neuroinflammation. Activation of the NLRP3 inflammasome, an important pattern recognition receptor in human innate immunity, plays a key role in the pathogenesis of vascular dementia.

The NLRP3 inflammasome pathway destroys neuronal cells primarily through the production of IL-18 and IL-1β. Moreover, it exacerbates vascular dementia by producing IL-18, IL-1β, and the N-terminal fragment of GSDMD, which also contributes to neuronal cell death. Thus, blocking the NLRP3 inflammasome pathway presents a new therapeutic strategy for treating vascular dementia, thereby delaying or curing the disease more effectively and mitigating adverse effects.

This review explores the role and mechanisms of the NLRP3 inflammasome in vascular dementia, summarizing current research and therapeutic strategies. Investigating the activation of the NLRP3 inflammasome can reveal the pathogenesis of vascular dementia from a new perspective and propose innovative preventive and treatment strategies.

Adjuvants, as a critical component of vaccines, are capable of eliciting more robust and sustained immune responses. Nanomaterials have shown unique advantages and broad application prospects in adjuvant development due to their high adjustability and distinctive physicochemical properties. This review focuses on nanoadjuvants and their immunological mechanisms. First, various types of adjuvants are introduced with an emphasis on metal and metal oxide nanoparticles, coordination polymers, liposomes, polymer nanoparticles, and other inorganic nanoparticles that can serve as vaccine adjuvants. Second, this review describes the current status of the clinical applications of nanoadjuvants. Next, the mechanisms of action for nanoadjuvants have been thoroughly elucidated, including the depot effect, NLRP3 inflammasome activation, targeting C-type lectin receptors, activation of toll-like receptors, and activation of the cGAS-STING signaling pathway. Finally, the challenges and opportunities associated with the development of nanoadjuvants have also been addressed.

This study investigated the mechanism underlying Paeonol's therapeutic efficacy against neuropathic pain. GSE158892 dataset data were used to conduct a scRNA-seq analysis. In cell experiments, Schwann cells and macrophages were utilized to examine pain pathogenesis using specific inhibitors. Thirty-two SD rats were randomly divided into four groups: sham, chronic constriction injury (CCI), ibuprofen, and Paeonol. Behavioral tests combined with ELISA, PCR, western blot, immunohistochemistry, and immunofluorescence analyses were conducted. CellChat analysis demonstrated that, following peripheral nerve injury, Schwann cells secreted IL-34, which interacted with CSF1R on macrophages, leading to the infiltration and activation of macrophages. Paeonol reduced IL-34 production by Schwann cells induced with LPS. Conditioned medium from LPS-stimulated Schwann cells treated with Paeonol did not cause macrophage proliferation or migration, activation of the CSF1 pathway, or ROS production. In CCI rats, Paeonol alleviated mechanical and cold hyperalgesia, while reducing the production of serum inflammatory mediators. Additionally, Paeonol decreased the expression levels of IL-34, CSF1R, phosphorylated ERK (p-ERK), phosphorylated NF-κB (p-NF-κB), and components of the NLRP3 inflammasome in the dorsal root ganglia of CCI rats. Conclusion: Alleviation of neuropathic pain by Paeonol treatment may be achieved by inhibiting the IL-34-CSF1R interaction, suppressing Schwann cell-macrophage interactions, and reducing DRG neuroinflammation.

Acute lung injury (ALI), which can progress to acute respiratory distress syndrome (ARDS), has inflammation as a crucial factor, especially the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome involvement. Stromal interaction molecule 1 (STIM1) can block NLRP3 activation, but the mechanism is unclear. Vanillic acid, possessing anti-inflammatory properties, has a role in acute lung injury (ALI) whose specific mechanism remains unclear. This study aimed to investigate the effectiveness of vanillic acid in ALI induced by lipopolysaccharides (LPS) and to elucidate the potential mechanisms. In vitro and in vivo experiments were conducted using cells and a mouse model to find out the impact and underlying mechanisms. We found that vanillic acid demonstrated significant inhibition of IL-1β and IL-18 release triggered by LPS and nigericin in J774A.1 cells. The in vivo findings indicated that vanillic acid not only mitigated acute lung injury but also suppressed NLRP3 inflammasome activation in mice. Mechanistically, vanillic acid inhibited the LPS-induced increase in STIM1 expression through the lysosomal degradation pathway. The reduced STIM1 expression diminished intracellular Ca2+ levels, thereby suppressing inflammasome activation and impeding the cleavage and maturation of Caspase-1 and GSDMD, and eventually attenuating cell pyroptosis. Vanillic acid exerts its inhibitory effects on NLRP3 inflammasome activation by promoting STIM1 degradation, thereby ameliorates ALI through impeding NLRP3-GSDMD mediated pyroptosis. The STIM1-NLRP3 signaling axis represents a promising avenue for potential therapeutic interventions in ALI.

JOURNAL/nrgr/04.03/01300535-202504000-00030/figure1/v/2024-07-06T104127Z/r/image-tiff Our previous studies have reported that activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been shown to restore the neuroinflammatory response, along with myelin and synaptic structural alterations in the prefrontal cortex, and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice. Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles, the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue, which inhibited the activation of the NLRP3 inflammasome, was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking. We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes (e.g., pyrin domain-containing 1, caspase recruitment domain-containing 4, and absent in melanoma 2, as well as the alterations in inflammatory genes (interleukin-1β, interleukin-18, inducible nitric oxide synthase, nuclear factor-kappa B, monocyte chemoattractant protein-1, and C-X3-C motif chemokine ligand 1) and miRNAs (miR-21a-5p, miR-146a-5p, and miR-141-5p) induced by binge-like ethanol treatment in adolescent mice. Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways. Taken together, these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Huang-Pu-Tong-Qiao (HPTQ), a Traditional Chinese Medicine formula, has achieved remarkable efficacy in clinically treating Alzheimer's disease (AD). Pyroptosis refers to the inflammatory necrosis of cells, which contributes to AD pathological progression. However, it is unclear whether the therapeutic effect of HPTQ on AD is related to reducing pyroptosis. In this study, the network pharmacology analysis was used to predict the molecular mechanism of HPTQ in treating AD and validated our hypothesis through mice and cell experiments. APP/PS1 transgenic mice and Aβ25-35-injured HT22 cells were used as AD models in vivo and in vitro. The pharmacological effects and mechanisms of HPTQ on AD were evaluated by Morris water maze, Y-maze, transmission electron microscope, immunofluorescence, Hoechst/PI staining, western blot, and ELISA. Network pharmacology reveals the correlation between the therapeutic effect of HPTQ on AD and the NOD-like receptor signaling pathway. In APP/PS1 mice, HPTQ reduced the escape latency and maintained cell membrane integrity. In HT22 cells, 15% HPTQ-medicated serum and 10 µM MCC950 increased cell viability and decreased PI positive rate compared with the Model group. In addition, HPTQ treatment in AD animal and cell models reduced the protein expressions of NLRP3, ASC, cleaved caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18. The experimental results of MCC950 specifically inhibiting the NLRP3 expression suggested that HPTQ might reduce neuronal pyroptosis by reducing NLRP3 inflammasome. Network pharmacology and experimental validation suggested that HPTQ alleviated NLRP3 inflammasome-mediated neuronal pyroptosis in AD, which could provide valuable candidate drugs for AD clinical treatment.

Activation of inflammasomes is the activation of inflammation‑related caspase mediated by the assembly signal of multi‑protein complex and the maturity of inflammatory factors, such as IL‑1β and IL‑18. Among them, the Nod‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most thoroughly studied type of inflammatory corpuscle at present, which is involved in the occurrence and development of numerous human diseases. Therefore, targeting the NLRP3 inflammasome has become the focus of drug development for related diseases. In this paper, the research progress of the NLRP3 inflammasome in recent years is summarized, including the activation and regulation of NLRP3 and its association with diseases. A deep understanding of the regulatory mechanism of NLRP3 will be helpful to the discovery of new drug targets and the development of therapeutic drugs.

Bipolar disorder (BD) is psychiatric disorder of not fully acknowledged pathophysiology. Studies show the involvement of innate-immune system activation and inflammation in BD course and treatment efficiency. Microglia are crucial players in the inflammatory response possibly responsible for BD innate-immune activity. Lithium is a mood stabilizer used in treatment for 75 years. Immunomodulation was previously described as one of the potential modes of its action. We hypothesized that lithium might modulate the microglia response to innate-immune-associated cytokines (10 ng/mL TNF-α, 50 ng/mL IL-1β, 20 ng/mL IFN-γ). We aimed to investigate whether lithium treatment and pretreatment of microglia modify the expression of genes associated with NLRP3 inflammasome. We also aimed to verify lithium treatment effect on caspase activity and extracellular IL-1β concentration. For the first time, our study used human microglial cell line - HMC3, the cytokine stimuli and lithium in concentration corresponding to that in the brains of patients. To analyze lithium mode of action, we analyzed the short- and long-term treatment and pretreatment. To assess the influence on microglia responding to innate-immune cytokines, we analyzed the expression of genes involved in innate-immune and inflammasome (TSPO, TLR4, NFKB1, CASP1, CASP4, NLRP3, IL-1β, IL-6), caspase activity, extracellular IL-1β concentration, phospho-GSK-3β(Ser9) expression and lactate concentration. We found that lithium treatment significantly reduced NLRP3 inflammasome-related genes expression. We observed that lithium treatment reduces inflammasome activity, which may attenuate the inflammatory state. Interestingly, the lithium pretreatment resulted in significantly elevated inflammasome activity, suggesting that lithium does not impair the immune response to additional stimuli.

Endometriosis (EMS) is a prevalent gynecological disease that leads to chronic pelvic pain and infertility in women of reproductive age. However, the underlying pathogenic genes and effective treatment for EMS remain unclear. Therefore, this study aims to identify key genes influencing the diagnosis and treatment of EMS. The GSE7307 dataset, comprising 18 EMS and 23 control samples, was obtained from the GEO database. Fourteen differential genes related to NOD-like receptor protein 3 (NLRP3) activation and EMS were extracted from endometrial samples in GSE7307 through differential analysis. GO and KEGG analyses revealed that these genes were primarily involved in the production and regulation of the cytokine IL-1β and the NOD-like receptor signaling pathway. Random Forest (RF) and support vector machine recursive feature elimination algorithms were employed to select four diagnostic markers related to NLRP3 activation (NLRP3, IL-1β, LY96, and PDIA3) for constructing the EMS diagnostic model. These markers were validated using western blotting and tested in GSE7305 and GSE23339 datasets. The AUC values demonstrated the model's robust diagnostic performance. Additionally, the infiltration of immune cells in the samples and the correlation between different immune factors and diagnostic markers were explored. These results suggest that the four diagnostic markers may also play a crucial role in EMS immunity. Finally, the DrugBank database indicated that niclosamide could be effective for NLRP3-targeted therapy. In conclusion, we identified four key diagnostic genes for EMS, and niclosamide emerged as a potential drug for NLRP3-targeted therapy in EMS.

Cardiomyopathies are a heterogeneous group of disorders that can lead to fulminant heart failure and sudden cardiac death. In recent years, the prevalence of all types of cardiomyopathies has shown an upward trend globally. Up to 40% of patients with cardiomyopathy-related heart failure have diabetes mellitus (DM). With the fast global spread of DM, the prevalence of DCM is increasing accordingly and it remains the leading cause of morbidity and mortality in chronic diabetic patients. NLRP3 inflammasome significantly contributes to the development and pathological progression of DCM. Targeting the inflammasome or any of the mediators along its activation pathway provides new potential therapeutic targets for developing specialized drugs to treat DCM.In this comprehensive review, we sought to introduce and summarize the non-coding RNAs with potential therapeutic effects targeting NLRP3 inflammasome signaling in DCM. We hope this general overview can aid future research in developing new therapies for DCM.

Periodontitis (PD) is a chronic infectious and inflammatory disease characterized by alveolar bone loss. The distinctive activity of immune cells critically exacerbates bone resorption in PD. Myeloid-derived suppressor cells (MDSCs) are known to contribute to various chronic inflammatory conditions, but their role in the pathogenesis and progression of PD remains poorly understood.

We used single-cell transcriptomic analysis with human gingival samples and animal models of experimental periodontitis to examine the role of M-MDSCs in PD. We also explored the therapeutic effect of depleting MDSCs on PD in vivo. Additionally, the mechanisms of long non-coding RNA Neat1 and the pathway of NF-κB-dependent "canonical NLRP3 inflammasome activation" in MDSCs were investigated in PD.

In this study, we revealed that monocytic (M)-MDSCs were significantly increased in inflamed gingiva of PD patients compared to healthy individuals. Expansion of M-MDSCs was also observed in the mouse model of ligature-induced periodontitis, and depletion of MDSCs in PD mice could ameliorate alveolar bone loss and reduce periodontal inflammation. Mechanistically, we found that long non-coding RNA Neat1 was significantly upregulated in M-MDSCs, which achieved this proinflammatory effect by activating NF-κB signaling in PD. Furthermore, the pathway of NF-κB-dependent "canonical NLRP3 inflammasome activation" was confirmed in the PD mouse model, accompanied by increased secretion of proinflammatory cytokines that drive alveolar bone loss, including IL-1β, IL-6 and TNF-α.

In conclusion, this study highlights the pivotal proinflammatory role of M-MDSCs in PD and suggests that targeting these cells may represent a novel immunotherapeutic approach. Future research could focus on strategies to specifically target MDSCs for the treatment of periodontitis.

Lipopolysaccharide (LPS) exacerbates liver injury by activating various inflammatory pathways. Clusterin, a glycoprotein involved in lipid transport, and cytoprotection, is known to have inhibitory effects on liver steatosis and fibrosis. In this study, we investigated the role of clusterin in regulating LPS-induced liver injury and its effects on liver injury in C57BL/6 mice and clusterin knockout mice injected with LPS for 3 h. Primary Kupffer cells (KCs) and hepatocytes (HCs) were isolated from these mice and examined using immunohistochemistry, real-time RT-PCR, ELISA, and western blot analysis to assess the effects of clusterin. Clusterin deficiency significantly exacerbated LPS-induced liver injury, as evidenced by increased inflammatory cell infiltration, elevated serum alanine aminotransferase and aspartate aminotransferase levels, and upregulated expression of pro-inflammatory cytokines and components of the NLRP3 inflammasome. By contrast, overexpression of clusterin in primary Kupffer cells and hepatocytes significantly reduced these inflammatory markers. Furthermore, the protective mechanism of clusterin involved inhibition of the STAT3 signaling pathway. These findings suggest that clusterin is a useful therapeutic target to modulate cytokine production and key inflammatory signaling pathways in inflammatory liver diseases.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are increasingly linked to mitochondrial dysfunction and neuroinflammation. Central to this link are mitochondrial damage-associated molecular patterns (mtDAMPs), including mitochondrial DNA, ATP, and reactive oxygen species, released during mitochondrial stress or damage. These mtDAMPs activate inflammatory pathways, such as the NLRP3 inflammasome and cGAS-STING, contributing to the progression of neurodegenerative diseases. This review delves into the mechanisms by which mtDAMPs drive neuroinflammation and discusses potential therapeutic strategies targeting these pathways to mitigate neurodegeneration. Additionally, it explores the cross-talk between mitochondria and the immune system, highlighting the complex interplay that exacerbates neuronal damage. Understanding the role of mtDAMPs could pave the way for novel treatments aimed at modulating neuroinflammation and slowing disease progression, ultimately improving patient outcome.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipid-rich plaques in arterial walls, leading to cardiovascular events such as myocardial infarction and stroke. Macrophage pyroptosis, a form of programmed cell death driven by the NLRP3 inflammasome and caspase-1 activation, plays a critical role in the progression and destabilization of atherosclerotic plaques. This review explores the molecular mechanisms underlying macrophage pyroptosis and their significant contributions to AS pathogenesis. Recent advancements have highlighted the therapeutic potential of targeting key components of the pyroptotic pathway, including the use of nanotechnology to increase drug delivery specificity. These strategies are promising for reducing inflammation, stabilizing plaques, and mitigating the clinical impact of AS. Future studies should focus on translating these findings into clinical applications to develop effective treatments that can halt or reverse AS progression by modulating macrophage pyroptosis.

Spinal cord injury (SCI) is a serious and disabling central nervous system injury that can trigger various neuropathological conditions, resulting in neuronal damage and release of various pro-inflammatory mediators, leading to neurological dysfunction. Currently, surgical decompression, drugs and rehabilitation are primarily used to relieve symptoms and improve endogenous repair mechanisms; however, they cannot directly promote nerve regeneration and functional recovery. SCI can be divided into primary and secondary injuries. Secondary injury is key to determining the severity of injury, whereas inflammation and cell death are important pathological mechanisms in the process of secondary SCI. The activation of the inflammasome complex is thought to be a necessary step in neuro-inflammation and a key trigger for neuronal death. The NLRP3 inflammasome is a cytoplasmic multiprotein complex that is considered an important factor in the development of SCI. Once the NLRP3 inflammasome is activated after SCI, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Inhibition of inflammasomes can effectively inhibit inflammation and cell death in the body and promote the recovery of nerve function after SCI. Therefore, inhibition of NLRP3 inflammasome activation may be a promising approach for the treatment of SCI. In this review, we describe the current understanding of NLRP3 inflammasome activation in SCI pathogenesis and its subsequent impact on SCI and summarize drugs and other potential inhibitors based on NLRP3 inflammasome regulation. The objective of this study was to emphasize the role of the NLRP3 inflammasome in SCI, and provide a new therapeutic strategy and theoretical basis for targeting the NLRP3 inflammasome as a therapy for SCI.

Huashi Baidu Granule (HSBDG), a traditional Chinese medicine (TCM), is used for treating coronavirus disease 2019 (COVID-19). Porcine reproductive and respiratory syndrome (PRRS) is considered the "COVID-19" for swine. According to the TCM theory, "dampness" is the main pathogenic factor in COVID-19 and PRRS, and "Huashi" means that this formula is good at removing "dampness". Studies have demonstrated that HSBDG's effect in COVID-19; but the mechanism of removing "dampness" remains elusive.

We aimed to assess the effect of HSBDG on PRRS, and elucidate its potential mechanism in removing "dampness".

We established a PRRS-virus (PRRSV)-infected Marc-145 cells model, and performed qRT-PCR, Western blot analysis, and indirect immunofluorescence assay to examine the anti-PRRSV effects of HSBDG in vitro. PRRSV-infected pig model was established and used to investigate HSBDG's effect in PRRS and explore underlying mechanisms in removing "dampness" using ELISA and immunohistochemistry assay methods.

HSBDG exhibited anti-PRRSV activity and suppressed the viral replication and release phases. HSBDG treatment alleviated PRRS, lowered rectal temperature, reduced histopathological changes and viral load in lung tissues, and ameliorated organ lesions. Moreover, IL-1β, IL-6, IL-8, and TNF-α expressions were decreased in lung tissues. Mechanistically, HSBDG inhibited the NLRP3/Caspase-1/GSDMD-N pathway to reduce the inflammatory response and upregulated AQP1, AQP5, α-ENaC, and Na-K-ATPase expressions to promote lung fluid clearance.

HSBDG exerted anti-PRRSV effects and could attenuate PRRS. HSBDG potentially removes "dampness" by attenuating inflammation by suppressing the NLRP3/Caspase-1/GSDMD-N pathway and inhibiting pulmonary edema by upregulating the expression of AQP1, AQP5, α-ENaC, and Na-K-ATPase.

Yunvjian (YNJ) decoction, a classic traditional Chinese medicine prescription for inflammatory diseases, has demonstrated good therapeutic effects in the clinical treatment of pneumonia. The aim of this study was to clarify the effective ingredients and mechanism of action of YNJ on lipopolysaccharide (LPS)-induced acute lung injury (ALI).

The effects of YNJ were evaluated in a mouse model of LPS-induced ALI and in LPS-treated MLE-12 murine lung epithelial cells and RAW264.7 macrophages in vitro. The mechanism of action of YNJ on these model systems was studied using RNA sequencing, immunohistochemical analysis, immunoblotting, immunofluorescence, ELISA, and polymerase chain reaction assays. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to identify the absorbed components of YNJ.

YNJ attenuated pulmonary damage in LPS-treated mice, as evidenced by reduced protein content in bronchoalveolar lavage fluid, decreased lung wet/dry weight ratio, and improved respiratory function. Analysis of pneumonia-related lung injury samples from patients in the Gene Expression Omnibus dataset GSE40012 indicated that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis was a primary mechanism in ALI. YNJ reduced the phosphorylation of nuclear factor-kappa B (NF-κB) and decreased the expression levels of lung NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and interleukin-1β levels (IL-1β) in vivo. Administration of YNJ-containing mouse serum increased cell viability and decreased malondialdehyde and reactive oxidative species contents in LPS-stimulated MLE-12 cells. YNJ-containing serum also decreased the secretion of tumor necrosis factor-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 macrophages, and promoted macrophage polarization toward an M2 phenotype. A total of 23 absorbed components were identified in YNJ-containing serum. Among those, network analysis and in vitro experiments indicated that diosgenin, timosaponin BII, and mangiferin are anti-inflammatory active substances.

YNJ attenuates LPS-induced ALI in mice by inhibiting pyroptosis of lung epithelial cells and macrophages via suppression of the NF-κB/NLRP3 pathway. Our findings provide novel insights into the therapeutic effects of YNJ on ALI.

The inflammasome is a cytoplasmic multiprotein complex that induces the maturation of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) or pyroptosis by activating caspases, which play critical roles in regulating inflammation, cell death, and various cellular processes. Multiple studies have shown that the inflammasome is a key regulator of the host defence response against pathogen infections. During the process of pathogenic microbe invasion into host cells, the host's innate immune system recognizes these microbes by activating inflammasomes, triggering inflammatory responses to clear the microbes and initiate immune responses. Moreover, microbial pathogens have evolved various mechanisms to inhibit or evade the activation of inflammasomes. Therefore, we review the interactions between viruses and microbes with inflammasomes during the invasion process, highlight the molecular mechanisms of inflammasome activation induced by microbial pathogen infection, and highlight the corresponding strategies that pathogens employ to evade inflammasome activity. Finally, we also discuss potential therapeutic strategies for the treatment of pathogenic microbial infections via the targeting of inflammasomes and their products.

Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β. The NLRP3 inhibitor MCC950 mitigated these effects without impacting NF-κB. Conversely, PPAR-γ knockdown intensified the inflammatory response. In vivo, α-amanitin induced dose-dependent liver injury in mice, evident by elevated serum ALT and AST, and histological liver damage. MCC950 pretreatment offered protection against hepatotoxicity, while PPAR-γ inhibition with GW9662 worsened the condition. The study highlights the interplay between α-amanitin, NLRP3, and PPAR-γ in hepatotoxicity, proposing potential therapeutic targets for mushroom poisoning-induced liver diseases.

The prevalence of osteoarthritis (OA) notably surges with age and weight gain. The most common clinical therapeutic drugs are painkillers, yet they cannot impede the deteriorating course of OA. Thus, understanding OA's pathogenesis and devising effective therapies is crucial. It is generally recognized that inflammation, pyroptosis, and OA progression are tightly linked. The activation of NLRP3 inflammasome can lead to the discharge of the pro-inflammatory cytokines Interleukin-1β and IL-18, intensifying subsequent inflammatory reactions and promoting OA development. Conversely, the imbalance caused by deacetylase-regulated NLRP3 inflammasome underlies the chronic mild inflammation related to degenerative diseases. Therefore, this article expounds on the mechanism of OA pathogenesis and the role of histone deacetylases (HDACs) in NLRP3 inflammasome-triggered OA, and illustrates the application of HDAC inhibitors in OA, striving to provide more insights into novel OA treatment approaches.

To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway.

The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy.

Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy.

TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.