NEUROSCIENCE
·
2024
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IF 2.9
Tao Ye,Ning Zhang,Yunting He,Chunyan Chen,Qiqi Zha,Anbang Zhang,Xiuqi Sun,Xuemei Wu
Cerebral ischemia–reperfusion injury is frequently associated with neuroinflammation. The modulation of microglial polarization presents a promising approach for addressing cerebral ischemia–reperfusion injury. While electroacupuncture preconditioning has demonstrated efficacy in the management of ischemic stroke, the underlying therapeutic mechanisms remain inadequately understood. The investigation focused on elucidating the relationship between alterations in the TLR4/NF-κB/TXNIP/NLRP3 signaling pathway and microglial polarization subsequent to EA pretreatment. Established a middle cerebral artery occlusion (MCAO) rat model following electroacupuncture (EA) treatment at the Baihui (GV 20) acupoint. Male Sprague-Dawley rats were randomly assigned to the sham, Ischemia/Reperfusion (I/R), I/R + EA groups (n = 6). The results of Nissl Staining and TUNEL Stainingl showed that the number of curative neurons increased significantly after pretreatment, indicating an improvement in neuron formation and an increase in the number of austenite. The level of apoptosis in brain tissue in the I/R group was significantly higher than that in the sham operation group. Electroacupuncture pretreatment can effectively inhibit apoptosis occurrence. In addition, electric acupuncture pretreatment protects rat blood–brain barrier integrity and mitochondrial function. After treatment, the number of M1-type microglia decreased, while the number of M2-type microglia increased. These results suggest that EA preconditioning may alleviate neurological deficits and neuronal apoptosis caused by cerebral I/R injury, while maintaining the integrity of the blood–brain barrier and promoting microglial polarization through the TLR4/NF-κB/TXNIP/NLRP3 signaling pathway. Our findings establish a new molecular mechanism and theoretical foundation for electroacupuncture therapy of ischemic stroke.
研究领域:
神经科学
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免疫学
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药理学
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中医
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DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·Vol. 29
·期 4
·1000-1011
·
IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Sheng Li,Shiyi Lu,Jiahui Xiong,Liang Chen,Yanting Lin,Xiaohui Chen,Xinyi Wang,Lijing Lin,Xiaoliang Cai,Xiaoyu Yang
Here, we systematically evaluated the therapeutic efficacy and mechanisms of action of in-house synthesized hydroxyethyl starch-curcumin nanoparticles (HES-CUR NPs) in ulcerative colitis (UC). Using a dextran sodium sulfate (DSS)-induced UC mouse model, we analyzed the effect of HES-CUR NPs on colonic tissue and the gut microbiota through the assessment of organ indices and serum biochemical markers, histopathology, immunohistochemistry, Western blot, and 16S rRNA sequencing. We found that HES-CUR NPs significantly suppressed the TLR4/NF-κB inflammatory pathway (downregulated TLR4, p-IKKβ, IL-1β, IL-6, NFKB, MyD88, and p-IKKB/IKKB; p < 0.01), activated the Nrf2/HO-1 antioxidant pathway (enhanced Nrf2 nuclear translocation and HO-1 expression), and upregulated the expression of tight junction proteins (claudin-1, occludin, ZO-1), thereby restoring intestinal barrier integrity. Microbiota analysis revealed that HES-CUR NPs increased gut microbiota diversity (elevated Chao1, Shannon, and ACE indices) and enriched beneficial bacteria abundance (Ligilactobacillus murinus, Lactobacillus johnsonii). Antibiotic intervention partially attenuated the therapeutic effects of the HES-CUR NPs, confirming that their effects involved microbiota-dependent mechanisms. Compared to CUR and SASP, HES-CUR NPs exhibited significantly enhanced bioavailability and efficacy (p < 0.01), attributed to the targeted delivery and sustained-release properties of the hydroxyethyl starch nanocarrier. No toxicity was observed, as indicated by normal spleen, liver, and thymus indices and stable levels of TP, ALT, AST, ALB, GLB, and ALB/GLB. Our findings indicated that HES-CUR alleviates UC through a synergistic, multi-target mechanism involving inflammatory pathway suppression, antioxidant pathway activation, intestinal barrier repair, and microbiota modulation, providing a theoretical foundation for developing efficient and safe natural nanomedicines targeting UC.
研究领域:
纳米医学
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胃肠病学
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免疫学
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药理学
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微生物学
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分子生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Sihao Zhang,Danmei Tian,Zixuan Xia,Fengge Yang,Yanhui Chen,Zhihong Yao,Yi He,Xinglong Miao,Guirong Zhou,Xinsheng Yao,Jinshan Tang
Ethnopharmacological relevance Chang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification. Aim of the study The objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D. Materials and Methods We first established the IBS-D rat model through neonatal maternal separation (NMS) in combination with restraint stress (RS) and the administration of senna decoction via gavage. To confirm the therapeutic effect of CKF on treating IBS-D, abdominal withdrawal reflex (AWR) scores, the quantity of fecal pellets, and the fecal water content (FWC) were measured to evaluate the influence of CKF on visceral hypersensitivity and the severity of diarrhea symptom after the intragastric administration of CKF for 14 days. Subsequently, enzyme linked immunosorbent assay (ELISA) was applied to assess the effect of CKF on neuropeptides substance P (SP) and 5-hydroxytryptamine (5-HT), as well as inflammatory cytokines in serum and in intestinal tissues. Further, colonic pathological changes, the amount of colonic mast cells, and the expression level of occludin in rat colon tissues, were investigated by hematoxylin-eosin (HE) staining, toluidine blue staining, and immunohistochemistry, respectively. To explore the underlying mechanisms, alterations in colonic RNA transcriptomics for the normal, model, and CKF treatment groups were assessed using RNA sequencing (RNA-Seq). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence (IF) assays were applied to validate the effect of CKF on predicted pathways in vivo and in vitro . In addition, to elucidate the potential active compounds in CKF, 11 representative components found in CKF were selected, and their anti-inflammation potentials were evaluated using LPS-treated RAW264.7 cell models. Results CKF treatment significantly reduced the number of fecal pellets, attenuated visceral hypersensitivity, and decreased 5-HT and SP concentrations in serum and colon tissues, along with a reduction in colonic mast cell counts, correlating with improved symptoms in IBS-D rats. Meanwhile, CKF treatment reduced the colonic inflammatory cell infiltration, lowered the levels of IL-6, TNF- α , and IL-1 β in serum and colon tissues, and increased the occludin protein expression in colon tissues to improve inflammatory response and colonic barrier function. RNA-Seq, in conjugation with our previous network pharmacology analysis, indicated that CKF might mitigate the symptoms of IBS-D rats by inhibiting the Toll like receptor 4/Nuclear factor kappa-B/NLR family pyrin domain-containing protein 3 (TLR4/NF- κ B/NLRP3) pathway, which was confirmed by WB, IF, and qRT-PCR experiments in vivo and in vitro . Furthermore, coptisine, berberine, hyperoside, epicatechin, and gallic acid present in CKF emerged as potential active components for treating IBS-D, as they demonstrated in vitro anti-inflammatory effects. Conclusion Our findings demonstrate that CKF effectively improves the symptoms of IBS-D rats, potentially through the inhibition of the TLR4/NF- κ B/NLRP3 pathway. Moreover, this study unveils the potential bioactive components in CKF that could be applied in the treatment of IBS-D.
研究领域:
药理学
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胃肠病学
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传统中药
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2017
·
IF 2.956
Ye Tian,Zheng Li,Bingyu Shen,Qiaoling Zhang,Haihua Feng
Morin , a bioactive flavonoid extracted from the bark of Moraceae plants and many medicinal herbs, has anti-inflammatory and antioxidative effects. In this research, we explored the protective effects of morin against lipopolysaccharide (LPS) and d -galactosamine (D-GalN) induced acute liver injury in mice. Mice were given an intraperitoneal injection of morin before LPS and D-GalN treatment and the HepG2 cells were only given morin to investigate its effects. The results showed that morin markedly inhibited the production of serum alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and hepatic TNF-α, IL-6, and myeloperoxidase (MPO) induced by LPS/D-GalN. In order to evaluate morin effect in the future, we investigated the expression of nuclear factor E2 related factor 2 (Nrf2), nuclear factor-kappaB (NF-κB), toll like receptor 4 (TLR4) on liver injury. Taken together, these results suggested that morin could exert the anti-inflammatory and anti-oxidative effects against LPS/D-GalN-induced acute liver injury by activating Nrf2 signal pathways and inhibiting NF-κB activation.
研究领域:
药理学
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免疫学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Chongchong Liu,Jiangyan Sun,Xiaoming Shen,Shefang Li,Sha Luo,Na Chen,Yunke Zhang
Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 μg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4–31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32–62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 μg/ml, 15 μg/ml, and 30 μg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.
研究领域:
神经病学
·
药理学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yingchun Zhao,Ying Qu,Changshun Huang,Chengzhilin Li,Wenyu Zhang,Xinyu Wang,Wenlong Duan,Qingbin He,Yachao Zhang,Jianwei Jiao,Runxiao Zheng
Systemic inflammation, excessive reactive oxygen species (ROS) and mitochondrial impairment are the main cause of multi-organ dysfunction syndrome in sepsis. Nevertheless, the pharmaceuticals currently in development focus solely on a single mechanism of disease, which is evidently inadequate. Herein, a precision nanodrug delivery system (MSe-NAD + /Nes) has been designed, incorporating mesoporous selenium nanozymes (MSe NPs) and leveraging a neutrophil-targeting strategy, to accomplish accurate delivery and mitigate inflammation. Upon reaching the inflammatory region, MSe NPs destroys selenium bonds and releases NAD + under the action of ROS, which in turn supplements the NAD + pool and promotes the recovery of mitochondrial function. Moreover, MSe NPs are capable of efficiently eliminating ROS by mimicking the activity of glutathione peroxidase (GPx), thus preventing the activation of the NLRP3 inflammasome. In vivo administration has indicated that MSe-NAD + /Nes efficiently alleviates organ oxidative stress, restores ATP levels, attenuates systemic hyperinflammation, and facilitates rapid organ repair. This study presents a potential modality of inflammation remission via ROS scavenging and mitochondrial repairment for the reliable and safe therapy of sepsis.
研究领域:
纳米医学
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免疫学
·
药理学
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炎症研究
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
·
IF 4.3
Xinhao Ye,Shiyi Duan,Hao Wang,Shimei Xiao,Mijia Li,Wei Yuan,Yan Zhao,Yiyue Zhang,Keyuan Zhong
The inflammatory response is a core protective physiological process against stimuli like infection or injury, and can be initiated by autoimmune disorders. It is primarily characterized by neutrophil-dominated leukocytosis and may lead to multiple organ dysfunction in severe cases. Environmental factors play an important role in the inflammatory response. Rare earth elements are not essential elements for living organisms. However, owing to large-scale mining and use, their concentrations in the environment have increased. Thus, rare earth elements are now considered emerging environmental pollutants, and the risks that rare earth elements pose to human health need further investigation. In this study, zebrafish were used as experimental animals, and zebrafish embryos were exposed to the different concentrations of lanthanum chloride (0, 5, 15, and 25 mg/L) to analyze its effect on embryo development and immune system. The number and distribution of zebrafish neutrophils as well as changes in oxidative stress and the expression of genes related to inflammation were analyzed. The results indicated that lanthanum chloride exposure reduced the heart rate, shortened the body length, and increased the yolk area of zebrafish embryos. In addition, exposure to lanthanum chloride caused the diffusion of neutrophils, leading to inflammation in zebrafish. Concurrently, the exposure led to the accumulation of reactive oxygen species in zebrafish, which subsequently resulted in the upregulation of malondialdehyde, catalase, and superoxide dismutase levels. Further experiments revealed that exposure to lanthanum chloride led to the upregulation of several inflammation-related genes, such as IL-6 , IL-8 , IL-10 , and cxcl-c1c , as well as certain TLR4/NF-κB signaling-related genes, including TLR4 , MyD88 , NF-κB P65 , IL-1β , and TNF-α . The TLR4/NF-κB signaling pathway inhibitor andrographolide can alleviate the inflammatory response induced by lanthanum chloride exposure. In conclusion, lanthanum chloride induced inflammation in zebrafish by activating the TLR4/NF-κB signaling pathway. The study results can provide a reference for evaluating the health risks of rare earth elements in humans.
研究领域:
毒理学
·
环境科学
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免疫学
·
分子生物学
·
水生毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 5.9
Jiangjiang Fu,Gangchen Cheng,Zhongxi Lyu,Zezhi Fan,Feiyang Li,Zhifang Xu,Bo Chen,Yongming Guo,Yuhan Liu,Hui Zhang,Yuan Xu,Yi Guo
Introduction: The acupuncture acupoint is the critical initial site for the therapeutic efficacy of electroacupuncture (EA). Previous studies have confirmed that the NF-κB pathway within the acupoint region mediates the therapeutic effects of acupuncture. Therefore, this study focuses on an in-depth investigation of the MD2/TLR4/NF-κB axis. Methods: The mouse model of adjuvant-induced arthritis (AIA) was established via intraplantar injection of Complete Freund’s Adjuvant (CFA). EA intervention was applied bilaterally to the Zusanli (ST36) acupoints, and behavioral, molecular, and immunological approaches were integrated to investigate the role of MD2 in EA-mediated analgesia. Results: EA increased paw thermal withdrawal thresholds (PTWTs) in AIA mice (P < 0.05), accompanied by higher levels of MD2, TLR4, p65, and the phosphorylated form of p65 (p-p65) at the acupoint. Co-immunoprecipitation (Co-IP) confirmed binding between MD2 and TLR4 in ST36 acupoint, while immunofluorescence (IF) revealed co-localization of TLR4 with fibroblasts and mast cells in ST36, suggesting these immune cells are critical targets for signal activation. Lentivirus-mediated knockdown of MD2 in the acupoint partially reversed EA’s analgesic effects and suppressed downstream TLR4/NF-κB pathway activation, whereas MD2 overexpression elicited a partial analgesic effect and promoted pathway activation. Together with spinal cord proteomics data, these findings indicate that modulating MD2 in the acupoint can regulate spinal cord-related signaling pathways. Mechanistically, EA dynamically regulates the equilibrium of the Grem1/BMP4/COX2 axis in the spinal dorsal horn via activation of the MD2/TLR4/NF-κB pathway cascade, achieving systemic analgesia. Conclusion: This study provides molecular evidence supporting the "acupoint priming" theory in acupuncture and highlights MD2 as a potential therapeutic target for pain management.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Menghan Wang,Liang Han,Dong Tian,Xinrui Meng,Zhanghui Guan,Zhuozhou Hu,Jia Kang,Xiaoshan Gao,Yixuan Zhang,Youquan Gu,Xiaohua Liu,Xinping Chen
Hyperuricemia (HUA), a prevalent metabolic disorder, is an independent risk factor for chronic kidney disease (CKD). Elevated serum uric acid (UA) level leads to renal UA deposition, causing kidney inflammation, impairing renal function, and accelerating HUA progression. In this study, an inflammation model in RAW264.7 cells induced by monosodium urate (MSU) was established to screen for compounds resistant to MSU-induced inflammation. Fortunately, 5-bromocytidine, a nucleic acid analogue, demonstrated potent anti-inflammatory activity in MSU-treated RAW264.7 cells and exhibited excellent therapeutic effects in HUA rats by reducing serum UA, creatinine (CRE) and blood urea nitrogen (BUN) amounts. Furthermore, we found that 5-bromocytidine blocked the activation of TLR4/NF-κB signaling pathway which mediated inflammation, and downregulated the expression of IL-1β and NLRP3. In summary, 5-bromocytidine may ameliorate HUA by suppressing the renal TLR4/NF-κB signaling pathway, suggesting a new candidate compound for HUA therapy.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Yu-Nan Lu,Xu-Dong Zhao,Xiang Xu,Jing Piao,Fumie Aosai,Ying-Biao Li,Long-Xie Shen,Su-Yun Shi,Guang-Hua Xu,Juan Ma,Hu-Nan Piao,Xuejun Jin,Lian-Xun Piao
Toxoplasmosis is a parasitic zoonosis with the highest incidence in humans. Severe lesions due to acute toxoplasmosis have been recorded in the visceral organs including the liver, where hepatocytes and Kupffer cells are important innate immune cells. Arctigenin (AG) is a bioactive ingredient of Arctium lappa L. and increasing evidence suggests that AG exhibits anti-oxidant, anti-inflammatory and anti- Toxoplasma gondii ( T. gondii ) effects. However, the role of AG in acute liver damage induced by T. gondii infection remains unclear. In this study, we analyzed the effects of AG against T. gondii -induced liver damage by establishing an in vitro infection model using a murine liver cell line (NCTC-1469 cells) and an in vivo mouse model with acute T. gondii infection of virulent RH strain. In the current study, AG effectively attenuated hepatocytes apoptosis and inhibited the reproduction of T. gondii . The results of in vitro and in vivo studies showed that AG significantly reduced alanine aminotransferase/aspartate aminotransferase activities and lessened pathological damage of liver. Moreover, AG suppressed T. gondii -induced inducible nitric oxide synthase production. AG also attenuated liver inflammation by inhibiting T. gondii -induced activation of the high-mobility group box1/toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway. These findings demonstrated that AG exhibited prominent hepatoprotective activities in toxoplasmic liver injury with anti-inflammatory effects by inhibiting the HMGB1/TLR4/NF-κB signaling axis. Thus, this study provides the basis for the development of new drugs to treat toxoplasmic hepatitis.
研究领域:
药理学
·
免疫学
·
寄生虫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2026
·
IF 3.1
Qingqing Xie,Xu Zhao,Yiwei Lu,Shiquan Shuai
Idiopathic pulmonary fibrosis (IPF) is a severe progressive lung disease with limited treatment options. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, possesses anti-inflammatory and anti-fibrotic properties, but its mechanism of action in pulmonary fibrosis (PF) remains incompletely understood. This study aimed to investigate whether DHEA alleviates PF by modulating macrophage-driven inflammatory responses. An in vitro model of PF was established using conditioned medium from LPS-stimulated, PMA-differentiated THP-1 macrophages to treat MRC-5 pulmonary fibroblasts. DHEA pretreatment (5–20 μM) was applied to macrophages, and the TLR4-specific inhibitor TAK-242 was used for mechanistic validation. Inflammatory cytokines were measured by ELISA, protein expression of TLR4/NF-κB/NLRP3 cascade components and extracellular matrix markers (α-SMA, Collagen I) by Western blotting, and cell proliferation by CCK-8 and flow cytometry. DHEA significantly reduced LPS-induced secretion of TNF-α, IL-6, IL-1β, and IL-18 from macrophages. It downregulated TLR4 expression, inhibited NF-κB phosphorylation, and suppressed NLRP3 inflammasome activation (NLRP3, ASC, Caspase-1). Furthermore, DHEA treatment of macrophages prevented their conditioned medium from inducing abnormal proliferation of MRC-5 cells and reduced α-SMA and Collagen I expression in these fibroblasts, similar to the effects of TAK-242. In conclusion, DHEA alleviates inflammatory responses and in vitro pulmonary fibrosis by blocking the TLR4/NF-κB/NLRP3 signaling cascade in macrophages, providing a new mechanistic basis for its potential therapeutic application in PF.
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DOI
PubMed
高影响因子
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