JOURNAL OF MEDICINAL CHEMISTRY
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2025
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IF 6.8
Xinlin Zhu,Yi Dong,Ya Zhang,Chenghai Gao,Lijian Ding,Yonghong Liu,Zhiran Ju
Gouty arthritis, driven by monosodium urate (MSU) crystal deposition and dysregulated inflammation, remains a therapeutic challenge due to the limitations of current treatments. Here, we investigate Herdmanine D (HDD), a marine-derived alkaloid from the ascidian Herdmania momus. It was optimized via structure–activity relationship (SAR) studies and computational modeling to enhance its binding to peroxisome proliferator-activated receptor γ (PPAR-γ), which regulates the PPAR-γ/NF-κB signaling pathway in gout pathogenesis. The optimized HDD derivative 9a demonstrated potent PPAR-γ binding affinity and pharmacokinetic properties, effectively suppressing NF-κB-driven pro-inflammatory cytokines in vitro. In murine MSU-induced gouty arthritis models, 9a alleviated synovial inflammation and tissue damage. Mechanistically, 9a activated PPAR-γ to inhibit NF-κB and attenuate NLRP3 inflammasome assembly. This work highlights HDD as a unique marine scaffold for next-generation antigout therapeutics, merging marine natural product safety with rational design to address unmet clinical needs.
研究领域:
药理学
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海洋天然产物
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炎症性疾病
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药物设计与开发
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风湿病学
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Pharmaceuticals
·
2026
·Vol. 19
·期 2
·325
·
IF 5.7
Yan Wang,Yuqin Peng,Hao Sun,Kai Zhu,Ning Wang,Changzhong Wang
Background : Plasma fibrinogen (FIB) levels exhibit a significant elevation during the acute phase of ischemic stroke (IS), and their dynamic fluctuations serve as important biomarkers for stroke onset, disease progression, and long-term prognosis. Tong-Qiao-Huo-Xue Decoction (TQHXD) is highly effective in treating blood stasis syndromes affecting the head and face. Nevertheless, the association between TQHXD and FIB in the underlying mechanism of treating IS warrants further investigation. Methods : Proteomics analysis predicted the potential therapeutic targets of TQHXD for IS. An in vivo model of middle cerebral artery occlusion followed by reperfusion (MCAO/R) was created in mice. To explore the interaction between FIB and NLRP3, as well as to verify the particular healing outcomes of TQHXD. Results : An increased blood–brain barrier (BBB) permeability was observed after MCAO/R, accompanied by substantial accumulation of FIB in the brain. In vivo experiments demonstrated that FIB triggered the activation of the NLRP3 inflammasome in microglia. Proteomic analysis revealed a significant increase in FIB levels following model induction, which were markedly reduced after treatment with TQHXD; KEGG pathway enrichment analysis indicated that these changes were primarily associated with the NOD-like receptor signaling pathway. Laser speckle contrast imaging showed that TQHXD treatment significantly improved cerebral blood flow and attenuated brain injury in mice. Fluorescence imaging, ELISA, and Western blotting results collectively demonstrated that TQHXD effectively reduced FIB accumulation and suppressed NLRP3 inflammasome activation. MD and pull-down experiments further demonstrated a strong interaction strength between FIB and NLRP3. Conclusions : FIB accumulates in the ischemic penumbra following CIRI, while TQHXD can effectively down-regulate FIB expression and inhibit NLRP3 inflammasome activation to mitigate CIRI. These findings provide a novel theoretical foundation and treatment direction for stroke management in clinical settings.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.4
Lili Wu,Siyu Chen,Qiyuan Yang,Xing Li,Lingyan Liu,Shengjun Ji,Shuaiyuan Tang,Sihui Zhang,Yan Wang,Runzhi Chen,Zhikun Zhan
Emodin, a bioactive compound abundant in Chinese medicinal herbs, possesses broad therapeutic potential but raises safety concerns due to conflicting reports of hepatotoxicity. This study investigated the toxicological mechanisms underlying emodin-induced liver injury. Emodin (25-100 μM) elicited dose-dependent cytotoxicity in HepG2 cells, with the cytochrome P450 (CYP) enzymes CYP1A2 and CYP3A4 identified as the primary enzymes metabolizing emodin into hydroxylated products (M1-M3). The comparative cytotoxicity assay of emodin and its metabolites in HepG2 cells indicated that CYP-mediated metabolism functions as a critical detoxification pathway. Moreover, inhibition of CYP with 1-aminobenzotriazole (ABT, 500 μM) markedly enhanced emodin (12.5-100 μM) cytotoxicity in HepG2 cells. Similarly, ABT (50 mg/kg) markedly exacerbated emodin (400 mg/kg)-induced hepatotoxicity in mice following three weeks of co-administration. Transcriptomic profiling and validation experiments demonstrated that activation of the NF-κB/NLRP3 signaling axis contributes to emodin-induced hepatic injury. Metabolomic analyses further revealed perturbations in key pathways, including lipopolysaccharide (LPS) biosynthesis, sphingolipid metabolism, and cholesterol metabolism. Integrated multi-omics analysis identified a significant positive correlation between these metabolites (LPS, sphingosine, cholesterol) and NF-κB/NLRP3 pathway genes. These findings suggest that emodin-mediated upregulation of LPS, sphingosine, and cholesterol activates the NF-κB/NLRP3 pathway, subsequently triggering hepatic injury. Collectively, this study delineates the metabolic detoxification routes of emodin and provides mechanistic insight into its hepatotoxic potential.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Jianyu Qu,Jian Fu,Yuanbin Wang,Xin Jiang,Ying Ma,Jine Yi,Jing Wu,Yunhuan Liu,Kehe Huang,Ji Wang,Zhihang Yuan,Lixin Wen,Shuiping Liu
Arsenic is an environmental contaminant with potent renal toxicity. Accumulating evidence has indicated that gut microbiota dysbiosis plays an important role in kidney disease. However, the role of gut microbiota in arsenic-exposure-induced renal injury remains unclear. In our study, chronic exposure to NaAsO2 and fecal microbiota transplantation (FMT) from NaAsO2-exposed mice increased intestinal permeability and elevated renal indoxyl sulfate (IS), a key metabolite of gut microbiota, which promoted renal fibrosis and activated the AhR/NLRP3 inflammasome signaling pathway. Moreover, AST-120, a non-specific adsorbent, alleviated chronic NaAsO2 exposure-induced renal fibrosis by reducing the IS level in mice. In HK-2 cells, IS mediated NaAsO2-induced fibrosis via the AhR/NLRP3 inflammasome signaling pathway. Collectively, we confirmed that chronic exposure to NaAsO2 caused renal fibrosis and intestinal barrier dysfunction. Meanwhile, the gut–kidney axis plays a significant role in the mechanism of NaAsO2-induced renal fibrosis, providing a new therapeutic target for the prevention and treatment of arseniasis.
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Applied Biological Chemistry
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2026
·Vol. 69
·期 1
·42
·
IF 4.2
Gao Xinyue,You Long,Qi Luyao,Jin Lei,Zhang Jianmei,Liu Yanan,Niu Zhiqiang
As a disease of high mortality rate, acute lung injury (ALI) has been getting increased attention. Heme oxygenase-1 (HO-1), which plays an essential role in alleviating the pathological symptoms of ALI. There have few studies noted that the improvement effect of HO-1 on ALI may associated to NOD-like receptor protein 3 (NLRP3) inflammasome. However, the roles of HO-1 in the process of NLRP3 inflammasome activation is remains unknown. This study investigated the mechanism that HO-1 blocking NLRP3 inflammasome in ALI. The sepsis model induced by LPS was used in C57BL6 mice, LPS triggered obviously pulmonary damage and edema formation, increased the expression of NLRP3 inflammasome component proteins and IL-1β, but those negative effects were reversed by the pretreatment of hemin. NOD-like receptor signaling pathway was down-regulated after hemin treatment through RNA-Seq. Meanwhile, hemin pretreatment exerted significantly inhibit effect on the activation of NLRP3 inflammasome, and the component proteins of NLRP3 inflammasome were not influenced in immortalization of bone marrow-derived macrophages (iBMDMs). Moreover, the immunoprecipitation and immunofluorescence experiments were indicated that HO-1 could bind to NLRP3, silencing HO-1 prevented the block effect of hemin on NLRP3 inflammasome activation. Our study suggested that hemin-inhibited NLRP3 inflammasome activation involved HO-1 bind to NLRP3 and alleviated ALI mice induced by LPS.
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Pharmaceuticals
·
2026
·Vol. 19
·期 7
·1083
·
IF 5.7
Xinying Qian,Fei Ye,Zhiyong Li,Hongzhu Chu,Zeng Xu,Wenyuan Peng,Xueya Liang,Hongchuan Zhao,Yan Tang,Pan Zhong,Yonggang Wei,Yinglan Zhao
Background: Pharmacological blockade of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as an attractive pharmacological strategy for a broad range of inflammatory and metabolic disorders. However, translating preclinical efficacy into clinical success remains a major bottleneck. We previously reported the discovery of a novel, potent NLRP3 inhibitor, KBD3536, but its in vivo efficacy across different pathological conditions remains uncharacterized. Here, we systematically evaluated the in vivo efficacy of KBD3536 across diverse preclinical models of NLRP3-related pathologies.Methods: KBD3536 was evaluated in established rodent models of monosodium urate (MSU)-induced acute inflammation (mouse air pouch and rat gouty arthritis models), radiation-induced dermatitis (RID), and high-fat diet (HFD)-induced obesity.Results: In the MSU models, KBD3536 markedly suppressed local interleukin-1β and interleukin-6 secretion in air pouch exudates and dose-dependently alleviated acute arthritis symptoms, including joint swelling and joint pain. In the RID model, KBD3536 significantly attenuated radiation-induced skin injury and ameliorated radiation-induced systemic weight loss. Under HFD challenge, early intervention with KBD3536 mitigated HFD-induced adiposity, early hepatic steatosis and its associated inflammatory responses, and preserved physical performance. Mechanistically, KBD3536 partially restored AMP-activated protein kinase α1 (AMPKα1) mRNA expression in adipose tissue and restored hepaticCyp3a11transcriptional activity.Conclusions: NLRP3 inhibitor KBD3536 exhibited broad-spectrum anti-inflammatory efficacy across multiple preclinical models, supporting its potential as a promising candidate for diverse NLRP3-related disorders.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
Chuanqi Wan,Jiamin Lu,Lingyun Xu,Mei Jiang,Chen Zhu,Wen Zhang,Pingping Han,Jirong Zhang,Jing Wang,Weiwei Ren,Hui Chu,Bingzhi Zhou,Jiancheng Zhang,Guangjun Jin,Bangjiang Fang,Yuzhou He
Shenhuang Granules (SHG) attenuate sepsis-induced lung injury via the NLRP3/Caspase-1/GSDMD pathway. • (−)-Epicatechin gallate and gallic acid are the core bioactive monomers of SHG against PMVEC pyroptosis. • SHG inhibits pyroptosis by suppressing inflammasome assembly and pore formation. Ethnopharmacological relevance Shenhuang Granules (SHG) is a traditional Chinese medicine (TCM) formula composed of six medicinal materials: Panax ginseng C.A. Mey. (Ginseng Radix et Rhizoma), Rheum palmatum L. (Rhei Radix et Rhizoma), Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson (Sargentodoxae Caulis), Taraxacum mongolicum Hand. -Mazz. (Taraxaci Herba), Aconitum carmichaelii Debeaux (Aconiti Lateralis Radix Praeparata), and Whitmania pigra Whitman (Hirudo). According to TCM theory, this formula is designed to replenish Qi and strengthen the body's resistance, clear heat and remove toxins, and promote blood circulation to eliminate blood stasis. In clinical practice, SHG has been used as an adjunctive therapy for sepsis, showing beneficial effects in ameliorating systemic inflammatory responses and microcirculatory disturbances. However, the underlying pharmacological mechanisms remain largely unclear. Aim of the study To validate that SHG and its active monomers alleviate sepsis-induced lung injury through targeted suppression of the NLRP3-driven PMVEC pyroptosis pathway. Materials and methods The chemical composition of SHG was analyzed by UHPLC-MS/MS. In vivo, SA-ARDS was induced in C57BL/6J mice by cecal ligation and puncture (CLP), with SHG (61.85 mg/mouse/d), its monomers, (−)-epicatechin gallate (ECG) and gallic acid (GA) (20 mg/kg/d), or the NLRP3 inhibitor MCC950 (10 mg/kg/d), were administered via intraperitoneal injection for 3 days prior to modeling. Lung injury severity and activation of the pyroptosis pathway were evaluated using histopathology, transmission electron microscopy, RT-qPCR, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. In vitro, LPS-stimulated (1 μg/mL) PMVECs were used to screen 43 monomers, and the underlying mechanisms were subsequently verified. Results Compared with the Model group, SHG treatment significantly attenuated body weight loss in mice ( P < 0.001), reduced the lung wet-to-dry (W/D) weight ratio ( P < 0.05), and decreased Evans blue extravasation in lung tissues ( P < 0.01). SHG also significantly downregulated the mRNA expression levels of pyroptosis-related genes, including Twik2 , Nlrp3 , Asc , Caspase-1 , and Gsdmd , in lung tissues (all P < 0.01), and markedly reduced the protein expression of NLRP3, ASC, pro-Caspase-1, and Caspase-1 (all P < 0.05). ELISA results further demonstrated that SHG significantly decreased serum levels of the inflammatory cytokines TNF-α, IL-1β, IFN-γ, IL-18, pro-IL-1β, and pro-IL-18 in mice (all P < 0.05). In vitro, compared with the Model group, SHG significantly suppressed the transcriptional levels of Twik2 , Nlrp3 , Asc , Caspase-1 , and Gsdmd in PMVECs (all P < 0.05), and reduced the protein expression of NLRP3, ASC, GSDMD, GSDMD-NT, and IL-1β (all P < 0.05). Additionally, SHG markedly decreased lactate dehydrogenase (LDH) release ( P < 0.0001) and attenuated extracellular potassium ion (K + ) efflux ( P < 0.0001). Notably, ECG and GA individually exhibited potent inhibitory effects on PMVEC pyroptosis. Compared with the Model group, both ECG and GA significantly suppressed mRNA expression of Twik2, Nlrp3, Asc, Caspase-1, and Gsdmd (all P < 0.05) and reduced protein levels of NLRP3 , ASC , Caspase-1 , and GSDMD (all P < 0.05). Moreover, ECG significantly inhibited GSDMD-NT and IL-1β protein expression (all P < 0.05). Both ECG and GA markedly reduced TNF-α, IL-1β, and pro-IL-18 levels (all P < 0.05), and GA additionally suppressed IL-18 and pro-IL-1β expression (all P < 0.01). Furthermore, both ECG and GA significantly decreased LDH release ( P < 0.0001) and inhibited extracellular K + efflux ( P < 0.0001). However, this study has several limitations, including a small sample size, the absence of dose-gradient and time-course analyses, insufficient functional validation of the TWIK2 channel, and the lack of quantitative pharmacokinetic and synergy analyses, which should be addressed in future studies. Conclusion Shenhuang Granules attenuated PMVEC pyroptosis and ameliorated sepsis-induced lung injury by suppressing TWIK2 and the downstream NLRP3/Caspase-1/GSDMD pathway, with GA and ECG as the key active components. Download: Download high-res image (484KB) Download: Download full-size image
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npj Parkinsons Disease
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2026
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IF 8.5
Zhang Shengyao,Wei Han,Wang Qiongfang,Zhang Meng,Wan Guoran,Wang Jian,Leng Jiajie,Li Jing,Chen Dilong,Huang Boyue,Ran Jianhua
Aging is frequently accompanied by cognitive decline and neuroinflammation, both of which are closely linked to dysbiosis of the intestinal microbiota. Ganoderma lucidum polysaccharides (GLPs), as natural bioactive compounds, exhibit anti-inflammatory, immunomodulatory, and neuroprotective properties. Recent studies suggest that GLPs may influence brain function via the gut-brain axis; however, the precise mechanisms underlying this effect remain unclear. This study demonstrates that GLPs alleviate cognitive impairment in aging mice through a gut-microbiota-dependent pathway. GLPs treatment enriched the butyrate-producing bacterium Blautia coccoides , elevated fecal acetyl-CoA and butyrate levels. Direct supplementation with Blautia coccoides or butyrate similarly improved cognition and suppressed neuroinflammation. GLPs notably ameliorated intestinal barrier damage and attenuated systemic inflammation. In the hippocampus, it inhibited microglial activation and NLRP3 inflammasome-mediated neuroinflammation. In NLRP3-knockout mice, these beneficial effects were not observed, thereby confirming that the pathway is NLRP3-dependent. Fecal microbiota transplantation from GLPs-treated donors replicated cognitive and anti-inflammatory effects in recipients, establishing microbial causality. Furthermore, butyrate and Blautia coccoides -derived metabolites directly suppressed NLRP3 activation in microglial cells in vitro. Our work defines a novel Blautia coccoides -butyrate-NLRP3 axis through which GLPs mitigates brain aging, supporting its potential as a prebiotic therapy for age-related cognitive disorders.
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Journal of Advanced Research
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2026
·
IF 17.1
Kean Lu,Zhenyan Cui,Xiaohong Fei,Jiahe Zhang,Shusen Fang,Yuwei Wang,Yaxia Chen,Yihua Wu,Dajing Xia
Introduction Per- and polyfluoroalkyl substances (PFASs) have been implicated in promoting the progression of intestinal inflammation. However, the specific mechanisms remain unclear. Objectives This study aimed to elucidate how PFASs exacerbate inflammatory bowel disease (IBD) progression by directly influencing macrophages, investigate the underlying molecular mechanisms, and explore potential interventions. Methods Primary mouse peritoneal macrophages (PMs) and a chronic colitis model were utilized to investigate the impacts of three typical PFASs, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), on the progression of IBD to clarify the underlying mechanisms and potential interventions. Results Our study found that PFNA induced significant proinflammatory responses, characterized by marked upregulation of IL-1β and IL-18 under environmentally relevant concentrations. Mechanistically, PFNA activated the caspase-11-dependent noncanonical NLRP3 inflammasome, thereby inducing dose-dependent upregulation of caspase-1, N-GSDMD, IL-1β, and IL-18. Both caspase-11 knockdown and Z-VAD-FMK inhibition attenuated these inflammatory effects. Molecular docking suggested that PFNA might induce NLRP3 inflammasome activation by interacting with pro-caspase-11. In vivo , PFNA also aggravated IBD progression through the same pathway. Conversely, based on our previous study, myricetin was found to alleviate PFNA-induced inflammation by inhibiting the caspase-11/NLRP3 axis. Conclusion Our study reveals a molecular axis through which PFNA exacerbates intestinal inflammation and identifies myricetin as a potential intervention for IBD associated with PFNA exposure. These findings provide insights into the mechanisms of PFNA-induced intestinal toxicity and may guide the development of strategies to mitigate PFNA-associated intestinal inflammation.
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EXPERIMENTAL ANIMALS
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2026
·
IF 2
Ying WANG,Yiqun JIANG,Simao SHI,Yu WANG,Jiyu YANG,Hongying KUANG,Xiaoling FENG
Vulvovaginal candidiasis, a common infection of the female reproductive tract, poses heightened risks when occurring during pregnancy (pVVC). Although Honghe Fujie lotion (HFL), a traditional Chinese medicine, is clinically used for mycotic vaginitis, its therapeutic efficacy and mechanisms in pVVC remain unclear. In this study, HPLC-MS was used to analyze and identify the compounds in HFL. This study investigated HFL’s effects through in vitro and in vivo approaches. A murine model of vaginal C. albicans infection was established to evaluate the therapeutic effect of HFL on pregnancy-associated vulvovaginal candidiasis (pVVC). Vaginal fungal load was quantified by analyzing vaginal lavage fluid, while the impact of HFL on adverse pregnancy outcomes was assessed through placental developmental analysis. Furthermore, the effects of HFL on pVVC-induced vaginitis and NLRP3 inflammasome activation were examined using immunofluorescence, enzyme-linked immunosorbent assay, and western blot. The results included: (1) High performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis identified 545 chemical constituents in HFL. (2) HFL significantly inhibited Candida albicans (C. albicans) growth and biofilm metabolic activity in vitro; (3) in a murine pVVC model, HFL reduced vaginal fungal load and mitigated adverse pregnancy outcomes, while also restoring trophoblast cell distribution in placental tissues; (4) mechanistically, HFL suppressed NLRP3 inflammasome activation, leading to Caspase-1 activity downregulation and subsequent impairment of pro-inflammatory cytokine secretion. These findings demonstrate that HFL alleviates pVVC by targeting the NLRP3 signaling pathway, providing a preclinical foundation for its therapeutic application in pregnancy-associated VVC.
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Journal of Pharmaceutical Analysis
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2026
·
IF 11.2
Yuejia Lan,Qingrui Zhong,Hongkai Huang,Xiao Deng,Lu Yang,Jiayi Sun,Mingyang Liu,Xianli Meng,Jiasi Wu
Evidence indicates that nuclear receptor subfamily 1 group H member 3 (NR1H3) activation mitigates sepsis-induced acute lung injury (SALI) by reducing inflammatory response. Nevertheless, the mechanisms underlying NR1H3-inflammation interactions in addressing SALI remain unclear. Moreover, limited phytochemicals have been documented to ameliorate SALI via this pathway. Here, we discovered that NR1H3 activation directly suppresses the clustering of toll-like receptor 4 (TLR4) to lipid rafts, which acts as a part of the priming of NLR family pyrin domain containing 3 (NLRP3) inflammasome. This process results in the suppression of NLRP3 inflammasome assembly and activation, consequently alleviating gasdermin-D (GSDMD)-mediated pyroptosis. Furthermore, through dual-luciferase reporter gene testing, drug binding assays, gene expression analysis, and biochemical evaluation, we determined lappaconitine hydrobromide (LAH) as a novel NR1H3 agonist that effectively suppresses TLR4-NLRP3 signaling pathway. Our results showed LAH attenuates inflammatory lung injury in both lipopolysaccharide and cecal slurry-induced SALI mouse models. In vivo and in vitro experiments revealed that LAH suppresses NLRP3 signaling activation and pyroptosis. Additionally, RNA-seq and bioinformatics analysis demonstrated that the differentially expressed genes (DEGs) linked to interleukin-1 beta (IL-1β) production, modulation of inflammatory response, and control of innate immune response were markedly enriched in LAH, and core genes amongst the DEGs included NR1H3. Mechanistically, LAH reduces inflammation and pyroptosis through modulation of NR1H3-NLRP3-GSDMD axis in mice. This finding was further substantiated by the suppression of NR1H3 in vitro . Our findings offer novel perspectives on the NR1H3-inflammation interaction in SALI regulation and indicate the therapeutic promise of LAH as an NR1H3 agonist for SALI management via NLRP3 suppression.
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MICROVASCULAR RESEARCH
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2025
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IF 2.7
Xiao Xu,Xiaohu Ge,Hongbo Ci,Maitiseyiti Abulaihaiti,JianPing Yang,YangYang Li,Feng Zhu
Background Thromboangiitis obliterans (TAO, Buerger's disease) is a chronic inflammatory disorder that affects small and medium-sized vessels in the limbs. Although the pathogenesis of TAO remains incompletely understood, elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with cardiovascular diseases. This study investigates the mechanism by which PAI-1 activates the NF-κB/NLRP3 inflammatory pathway in vascular endothelial cells through hypoxia-inducible factor-1α (HIF-1α), contributing to the progression of TAO. Methods Proteomic analysis was performed on plasma samples from 5 TAO patients and 5 healthy controls to identify differentially expressed proteins (DEPs). In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to 1 % hypoxia to mimic TAO conditions. Interventions included PAI-1 knockdown using lentiviral vectors and treatment with the HIF-1α agonist dimethyloxalylglycine (DMOG). Cell viability was assessed using the CCK-8 assay, apoptosis was measured by flow cytometry, and inflammatory factor levels were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression was analyzed by Western blotting. In vivo, a TAO rat model was established by sodium laurate injection. The severity of limb ischemia was evaluated using gross lesion grading and infrared thermography, while pathological changes were assessed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Results Elevated levels of PAI-1, HIF-1α, and key molecules in the NLRP3/NF-κB pathway were observed in both TAO rats and hypoxic HUVECs. PAI-1 knockdown significantly improved limb ischemia and suppressed the NLRP3/NF-κB pathway in TAO rats. Compared with the DMOG intervention group, combined treatment with PAI-1 knockdown and DMOG effectively alleviated ischemic symptoms, increased body weight, and reduced the expression of HIF-1α and inflammatory pathway molecules in TAO rats. Conclusion PAI-1 promotes the progression of TAO by activating the NF-κB pathway via HIF-1α. Targeted inhibition of PAI-1 represents a potential therapeutic strategy for TAO.
研究领域:
心血管医学
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分子生物学
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炎症研究
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血管生物学
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