Inflammation最新文献

{"title":"Biological Clock Perspective in Rheumatoid Arthritis.","authors":"Qingxue Liu, Yihao Zhang","doi":"10.1007/s10753-024-02120-4","DOIUrl":"https://doi.org/10.1007/s10753-024-02120-4","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic polyarticular pain, and its main pathological features include inflammatory cell infiltration, synovial fibroblast proliferation, and cartilage erosion. Immune cells, synovial cells and neuroendocrine factors play pivotal roles in the pathophysiological mechanism underlying rheumatoid arthritis. Biological clock genes regulate immune cell functions, which is linked to rhythmic changes in arthritis pathology. Additionally, the interaction between biological clock genes and neuroendocrine factors is also involved in rhythmic changes in rheumatoid arthritis. This review provides an overview of the contributions of circadian rhythm genes to RA pathology, including their interaction with the immune system and their involvement in regulating the secretion and function of neuroendocrine factors. A molecular understanding of the role of the circadian rhythm in RA may offer insights for effective disease management.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B Cells Infiltration Potentially Responded Better to Systemic Corticoids in Oral Lichen Planus and Oral Lichenoid Lesions.","authors":"Ming-Hua Feng, Yi-Rao Lai, Yi-Wen Deng, Xi-Ye Li, Lei Pan, Zhen Tian, Guo-Yao Tang, Yu-Feng Wang","doi":"10.1007/s10753-024-02112-4","DOIUrl":"https://doi.org/10.1007/s10753-024-02112-4","url":null,"abstract":"<p><p>Oral lichen planus (OLP) and oral lichenoid lesion (OLL) are chronic inflammatory diseases involving the oral mucosa. B cells infiltration in OLP and OLL, however, little is known about these cells in OLP and OLL. To analyze the function and infiltrating features of B lymphocytes in OLP and OLL, and to preliminarily evaluate their correlation with clinical outcomes. Tissue samples were collected from OLP, OLL, and healthy mucosa. The phenotypes and amounts of B cells in tissues were analyzed by single-cell sequencing. Their proportion and infiltrating features in tissues were examined by immunohistochemistry and immunofluorescence. With the systemic medication of corticoids, the correlation between B cells infiltrating characteristics and the clinical outcomes were evaluated. A quantified proportion increase of B cells was shown in both OLP and OLL. B cells in OLP demonstrated heightened activation and enhanced regulation in immune response. A cohort of 100 patients with OLP/OLL and 13 healthy controls were examined to investigate the B cells infiltration pattern. B cells were distributed in the superficial layer of lamina propria in 92.9% and 41.9% of OLP and OLL, respectively(P < 0.01); focally distributed in 25.0% and 62.9% of OLP and OLL, respectively(P < 0.01). With the systemic medication of corticoids, the cases with B cell infiltration (B⁺) in OLP and OLL groups showed a statistically significant reduction in REU scores before and after treatment (P < 0.01). B cells are widely present in OLP and OLL, and B cell infiltration in OLP and OLL are related to the better therapeutic effect of oral corticoids.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.","authors":"Shenglong Mo, Chengmin Yang, Xingwu Zheng, Hui Lv, Sanyin Mao, Ning Liu, Qin Yang, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Xuebin Li, Jingwei Shang","doi":"10.1007/s10753-024-02082-7","DOIUrl":"https://doi.org/10.1007/s10753-024-02082-7","url":null,"abstract":"<p><p>Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the S1P/S1PR1 Signaling Pathway on High Glucose-Induced NRK-52E Epithelial-Mesenchymal Transition Via Regulation of ROS/NLRP3.","authors":"Jihua Tian, Jingshu Chen, Qiuyue Sun, Taiping Huang, Huanyu Xu, Jing Wang, Zhijie Ma","doi":"10.1007/s10753-024-02118-y","DOIUrl":"https://doi.org/10.1007/s10753-024-02118-y","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is the most significant complication in diabetic patients, ultimately leading to renal fibrosis. The most important manifestation of DKD is the epithelial-mesenchymal transition (EMT) of renal tubular cells, which can lead to renal fibrosis and inflammatory injury in special situations. Sphingosine 1-phosphate (S1P) is involved in various signal transduction pathways and plays a role through G protein-coupled receptors. Research has demonstrated that blocking the S1P / S1PR2 pathway inhibits inflammation and fibrosis. However, the interaction between S1P/S1PR1 and the pathophysiology of EMT remains ambiguous. The purpose of this study was to investigate the mechanism of S1P/S1PR1 on high glucose (HG)-induced renal EMT. We found that HG markedly increased the S1P and EMT marker levels in renal tubular epithelial cells. At the same time, HG could stimulate NF-κB/ROS/NLRP3 expression, but these phenomena were reversed after blocking S1PR1. In mice models of DKD, FTY720 (S1P antagonist) could significantly improve renal function and reduce the infiltration of inflammatory cells. ROS, as well as NLPR3 inflammasome, were markedly decreased in the treatment group. FTY720 inhibits extracellular matrix synthesis and improves renal fibrosis. In brief, the HG stimulates S1P/S1PR1 synthesis and activates the S1P/S1PR1 pathway. Through the S1P/S1PR1 pathway, activates NF-κB, promotes ROS generation and NLRP3 inflammasome activation, and ultimately causes EMT.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZC3H13-Mediated m6A Modification Ameliorates Acute Myocardial Infarction through Preventing Inflammation, Oxidative Stress and Ferroptosis by Targeting lncRNA93358.","authors":"Jiumei Cai, Xiaoping Wang, Ziliang Wang, Shanhui Sheng, Fosheng Tang, Zhiwei Zhang","doi":"10.1007/s10753-024-02116-0","DOIUrl":"https://doi.org/10.1007/s10753-024-02116-0","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) is a life-threatening event that is associated with RNA modification and programmed cell death (PCD). This study attempted to investigate the impacts of zinc finger CCCH domain-containing protein 13 (ZC3H13)-mediated N6-methyladenosine (m6A) on ferroptosis in AMI.</p><p><strong>Methods: </strong>The infarcted areas and cardiac function were evaluated, and the expression level of ZC3H13 was measured in AMI rats that were induced by isoproterenol. Meanwhile, oxygen glucose deprivation (OGD) in vitro model was induced to investigate the alterations on inflammation, oxidative stress and ferroptosis. The m6A modification site of lncRNA93358 modified by ZC3H13 was predicted using bioinformatics, and the interaction between ZC3H13 and lncRNA93358 was verified using the dual-luciferase reporter assays. ZC3H13 was overexpressed and lncRNA93358 was silenced to study their regulatory role in cell death, inflammation, oxidative stress and ferroptosis in AMI.</p><p><strong>Results: </strong>Significant decreased expression of ZC3H13 was observed in AMI rats, with impaired cardiac function, enhanced inflammation and oxidative stress. ZC3H13 targeted the modification site GGACC of lncRNA93358 and downregulated lncRNA93358. Silencing lncRNA93358 inhibited cell death, reduced the levels of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, suppressed oxidative stress-related indicators (lactate dehydrogenase (LDH), reactive oxygen species (ROS), glutathione (GSH) and malondialdehyde (MDA), as well as downregulated ferroptosis-related acyl-CoA synthetase long chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2) and glutathione peroxidase 4 (GPX4). The effect of silencing lncRNA93358 was further enhanced by overexpression of ZC3H13.</p><p><strong>Conclusion: </strong>This study reveals the ZC3H13-mediated epigenetic RNA modification targeting lncRNA93358 and suggests that ZC3H13 overexpression may be a promising approach for AMI treatment.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-146a (rs2910164) Gene Polymorphism and Its Impact on Circulating MiR-146a Levels in Patients with Inflammatory Bowel Diseases.","authors":"Rasha Ahmed Ghorab, Shaimaa H Fouad, Ahmed F Sherief, Eman M El-Sehsah, Sara Shamloul, Sara I Taha","doi":"10.1007/s10753-024-02108-0","DOIUrl":"https://doi.org/10.1007/s10753-024-02108-0","url":null,"abstract":"<p><p>MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association of miR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive. Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?","authors":"Fatemeh Zarimeidani, Rahem Rahmati, Mehrnaz Mostafavi, Mohammad Darvishi, Sanaz Khodadadi, Mahya Mohammadi, Farid Shamlou, Salar Bakhtiyari, Iraj Alipourfard","doi":"10.1007/s10753-024-02061-y","DOIUrl":"https://doi.org/10.1007/s10753-024-02061-y","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM35 Negatively Regulates the cGAS-STING-Mediated Signaling Pathway by Attenuating K63-Linked Ubiquitination of STING.","authors":"Jikai Zhang, Yuhao Wu, Yiwen Wang, Jing Wang, Yinlin Ye, Hang Yin, Ningye Sun, Baoying Qin, Nan Sun","doi":"10.1007/s10753-024-02093-4","DOIUrl":"https://doi.org/10.1007/s10753-024-02093-4","url":null,"abstract":"<p><p>The cGAS-STING-mediated antiviral response plays an important role in the defense against DNA virus infection. Tripartite motif protein 35 (TRIM35), an E3 ubiquitin ligase, was identified as a positive regulator of RLR-mediated antiviral signaling in our previous study, but the effect of TRIM35 on the cGAS-STING signaling pathway has not been elucidated. Herein, we showed that TRIM35 negatively regulates the cGAS-STING signaling pathway by directly targeting STING. TRIM35 overexpression significantly inhibited the cGAMP-triggered phosphorylation of TBK1 and IRF3, attenuating IFN-β expression and the downstream antiviral response. Mechanistically, TRIM35 colocalized and directly interacted with STING in the cytoplasm. TRM35 removed K63-linked ubiquitin from STING through the C36 and C44 sites in the RING domain, which impaired the interaction of STING with TBK1 or IKKε. In addition, we demonstrated that the RING domain is a key region for the antiviral effects of TIRM35. These results collectively indicate that TRIM35 negatively regulates type I interferon (IFN-I) production by targeting and deubiquitinating STING. TRIM35 may be a potential therapeutic target for controlling viral infection.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albiflorin Attenuates Neuroinflammation and Improves Functional Recovery After Spinal Cord Injury Through Regulating LSD1-Mediated Microglial Activation and Ferroptosis.","authors":"Longyu Zhang, Jiao Xu, Shi Yin, Qiang Wang, Zhiwei Jia, Tianlin Wen","doi":"10.1007/s10753-024-01978-8","DOIUrl":"10.1007/s10753-024-01978-8","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious, prolonged, and irreversible injury with few therapeutic options. Albiflorin (AF) possesses powerful pharmacodynamic properties and exerts protective effects against neuroinflammation. However, no research has examined the neuroprotective effect of AF following SCI. Rats were received laminectomy to establish SCI animal model and treated with AF (20 mg/kg and 40 mg/kg). Behavioral experiments were conducted to assess the impacts of AF on motor function after SCI in rats. Hematoxylin-eosin (HE) staining, Nissl staining, and Prussian Blue staining were performed to observe histological changes, neuronal damage, and iron deposition, respectively. Transmission electron microscope was adopted to observe the ultrastructure of spinal cord tissues. Immunofluorescence assay was performed to examine neurons and microglia. ELISA assay was used to examine the production of cytokines. Western blot assay was used to detect the expression level of ferroptosis-related proteins. Microglia BV-2 cells were induced by LPS to mimic the neuroinflammatory condition. Cell viability was assessed by CCK-8 assay, and lipid peroxidase level was measured by C11 BODIPY 581/591 staining. Molecular docking technology was utilized to confirm the relationship between AF and LSD1. AF improved the motor functional recovery after SCI in rats. Meanwhile, AF attenuated neuron apoptosis and microglia activation, reduced the production of pro-inflammatory cytokines and iron accumulation, and inhibited spinal cord ferroptosis following SCI in rats. LSD1 was verified to be a target protein of AF, and AF could concentration-dependently downregulate LSD1 expression in injured spinal cords in vivo and LPS-induced BV-2 cells in vitro. In addition, AF not only inhibited ferroptosis through reducing lipid peroxidase and iron levels and regulating ferroptosis-related proteins, but also inhibited microglial activation and reduced pro-inflammatory cytokines production in LPS-induced BV-2 cells; however, these changes were partly counteracted by LSD1 overexpression. AF could reduce microglial activation and ferroptosis, attenuate neuroinflammation, and improve functional recovery following SCI by downregulating LSD1, providing novel therapeutic strategies for the treatment of SCI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1313-1327"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phillygenin Inhibits TGF-β1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/β-catenin Pathways.","authors":"Cheng Wang, Shenglin Zhang, Yanzhi Li, Lihong Gong, Chenhao Yao, Ke Fu, Yunxia Li","doi":"10.1007/s10753-024-01984-w","DOIUrl":"10.1007/s10753-024-01984-w","url":null,"abstract":"<p><p>Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C₂₁H₂₄O₆) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-β1 (TGF-β1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-β1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-β1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/β-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1403-1422"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}