Zhifeng Geng , Guoyi Deng , Ziyu Wang, Xin Xu, Xiaojiao Yin, Sen Zhang, Jiale Shao, Jiyue Wen
{"title":"Distinct roles of A1/A2 astrocytes in blood-brain barrier injury following cerebral I/R via the ROCK/NF-κB and STAT3 pathways","authors":"Zhifeng Geng , Guoyi Deng , Ziyu Wang, Xin Xu, Xiaojiao Yin, Sen Zhang, Jiale Shao, Jiyue Wen","doi":"10.1016/j.intimp.2025.114338","DOIUrl":"10.1016/j.intimp.2025.114338","url":null,"abstract":"<div><div>Astrocytes may fail to perform their neuroprotective roles against cerebral ischemia/reperfusion (I/R) injury due to phenotypic transformation. We aimed to demonstrate the distinct roles of A1 astrocytes and A2 astrocytes on the blood-brain barrier (BBB) injury following cerebral I/R, and explore whether H<sub>2</sub>S-mediated A2 astrocytes polarization protects against BBB injury via inhibiting ROCK/NF-κB pathway. The mice cerebral I/R model and the oxygen-glucose deprivation/re‑oxygenation (OGD/R) model of astrocytes were used in present study. Cerebral I/R-induced BBB injury is evidenced by increased EB dye leakage and reduced expressions of ZO-1 and occludin in mice hippocampal tissues. We found that H<sub>2</sub>S-mediated A2 polarization and lipopolysaccharide (LPS)-induced polarization of A1 astrocytes respectively display beneficial and harmful role in BBB injury. Besides, harmful roles of A1 astrocytes in BBB injury can be reduced by H<sub>2</sub>S. Additionally, A1 astrocytes exhibit excessive activation of NF-κB and enhanced expressions of MMP9 and AQP4, which can be inhibited by H<sub>2</sub>S. Moreover, H<sub>2</sub>S-mediated polarization of A2 astrocyte displays enhanced phosphorylation and nuclear translocation of STAT3 and reduced expressions of MMP9 and AQP4. Importantly, ROCK inhibitor Fasudil likewise inhibits the activation of NF-κB and promotes STAT3 activation in OGD/R astrocytes, and NF-κB inhibitor BAY11–7082 reduces the expressions of MMP9 and AQP4 in OGD/R astrocytes. In conclusion, H<sub>2</sub>S-mediated polarization of A2 astrocyte protects against BBB injury following cerebral I/R, the mechanisms may be related to inhibition of ROCK/NF-κB pathway, and activation of STAT3.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114338"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509161","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}
Xing Zhou , Yu Pan , Jinlei Li , Rujie Zhuang , Peijian Tong , Hanting Xia
{"title":"Notopterol mitigates osteoarthritis progression and relieves pain in mice by inhibiting PI3K/Akt/GPX4-mediated ferroptosis","authors":"Xing Zhou , Yu Pan , Jinlei Li , Rujie Zhuang , Peijian Tong , Hanting Xia","doi":"10.1016/j.intimp.2025.114323","DOIUrl":"10.1016/j.intimp.2025.114323","url":null,"abstract":"<div><div>Ferroptosis-induced lipid peroxidation in chondrocytes exacerbates intra-articular inflammation, oxidative stress, and articular cartilage degradation, accelerating osteoarthritis (OA) progression. Effective anti-inflammatory and antioxidant interventions can alleviate both joint pain and cartilage damage. This study aims to elucidate the therapeutic effects of Notopterol (NP), a bioactive compound extracted from the rhizome of <em>Notopterygium incisum</em>, a traditional Chinese medicine known for its potent anti-inflammatory and antioxidant properties, in treating OA. An in vivo mouse model of OA was established through medial meniscus destabilization (DMM). Intra-articular injections of NP over a 4-week treatment period significantly alleviated pain and gait abnormalities, reduced subchondral osteosclerosis, and attenuated cartilage degradation compared to the untreated DMM group. In vitro, chondrocytes treated with IL-1β to simulate OA conditions exhibited increased viability following NP pretreatment, with concurrent reductions in apoptosis, reactive oxygen species (ROS) accumulation, and chondrocyte catabolic dysfunction, along with enhanced extracellular matrix (ECM) synthesis. Mechanistically, NP exerts its anti-OA effects by inhibiting PI3K/Akt phosphorylation, suppressing ferroptosis, and improving antioxidant defense via upregulation of glutathione (GSH) and glutathione peroxidase 4 (GPX4), thereby preventing lipid peroxidation. In conclusion, NP modulates the PI3K/Akt/GPX4 axis to protect against lipid peroxidation, inhibit ferroptosis, and preserve cartilage integrity, thus delaying OA progression.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114323"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508959","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}
Xiaolin Ma , Xuan Zhao , Yulong Yang , Jinjin Yan , Xiaoyan Shi , Hongfei Wu , Yarong Liu , Min Dai
{"title":"Paeonol inhibits NETs-mediated foam cell inflammation through the CitH3/NLRP3/caspase-1 signaling pathway in atherosclerosis","authors":"Xiaolin Ma , Xuan Zhao , Yulong Yang , Jinjin Yan , Xiaoyan Shi , Hongfei Wu , Yarong Liu , Min Dai","doi":"10.1016/j.intimp.2025.114340","DOIUrl":"10.1016/j.intimp.2025.114340","url":null,"abstract":"<div><div>Atherosclerosis is a chronic inflammatory disease characterized by lipid streaks, which are produced by aggregates of lipid-rich foam cells. Foam cells intensify atherosclerosis by secreting a range of inflammatory mediators. Neutrophil extracellular traps produced by activated neutrophils, which are abundantly present in lipid-accumulating plaques. However, the relationship between neutrophil extracellular traps and foam cells inflammation is still unclear. Paeonol is well known for its anti-inflammatory effects in atherosclerosis. Nevertheless, the exact pharmacological mechanisms by which paeonol affects atherosclerosis are not fully understood which require further investigation. The purpose of this study is to investigate the effects of paeonol on the neutrophil extracellular traps' formation and foam cell inflammation caused by neutrophil extracellular traps, and to explore the potential mechanisms. A high-fat diet was administered to ApoE<sup>−/−</sup> mice for a period of 12 weeks to induce an atherosclerosis model. Our findings demonstrated that paeonol notably suppressed the advancement of atherosclerosis in ApoE<sup>−/−</sup> mice, curtailed the formation of neutrophil extracellular traps, and lowered inflammatory factor levels within the plaque. <em>In vitro</em> studies have shown that neutrophil extracellular traps could enhance the inflammation in foam cells. CitH3 played a role in the cellular communication between neutrophil extracellular traps and foam cells. Concurrently, NLRP3 acted as a key receptor in the inflammation mediated by this interaction. Paeonol is capable of regulating NE, thereby affecting the formation of neutrophil extracellular traps. Most notably, the foam cell inflammation caused by neutrophil extracellular traps was significantly mitigated by the inclusion of paeonol. Our findings suggested that paeonol inhibited foam cell inflammation which induced by neutrophil extracellular traps through the CitH3/NLRP3/caspase-1 signaling pathway, shedding new lights on its anti-atherosclerotic pharmacological mechanism.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114340"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508967","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}
Jiacheng Lv , Huilin Quan , Jiarui Lv , Yanan Sui , Panpan Yu , Shu Guo , Yuwei Miao , Mengzhu Lv
{"title":"Argatroban and Menadione exert protective effects in ultraviolet-irradiated skin inflammation: A transcriptomic analysis based on identification of iron overload related biomarkers","authors":"Jiacheng Lv , Huilin Quan , Jiarui Lv , Yanan Sui , Panpan Yu , Shu Guo , Yuwei Miao , Mengzhu Lv","doi":"10.1016/j.intimp.2025.114334","DOIUrl":"10.1016/j.intimp.2025.114334","url":null,"abstract":"<div><div>Ultraviolet light (UV) can cause serious damage to human skin. The inflammatory reaction arising from repeated UV exposure leads to severe skin lesions and even promotes photo-carcinogenesis. Iron overload is featured by excessive iron intake and deposition and will promote inflammatory response inside cells. However, the core molecules involved in UV radiation induced iron overload and related anti-inflammatory strategies remain unclear. Signature genes involved in UV-irradiated skin were filtered through integrated datasets from the Gene Expression Omnibus (GEO) database. Subsequently, immune cell infiltration analysis was carried out to examine the relationship between signature gene expression and immune cell abundance. Single cell RNA-seq matrix data implicated in UV-irradiated skin was then applied to assess the expression level of signature genes in different cell clusters and to find out the core cell type and the key signaling pathway involved in UV radiation. Finally, cytological and animal experiments were conducted to investigate the potential of signature genes as therapeutic targets. SAT1 and RBMS1 were screened and validated as signature genes of UV irradiation. Immune cell infiltration analysis demonstrated that SAT1 and RBMS1 expression were associated closely with immune cell abundance, and skin fibroblasts were identified as the central cell type to communicate with other cell clusters in UV-irradiated skin. Disturbance of SAT1 exerted observably more suppressive effects on the release of inflammatory cytokines than overexpression of RBMS1. Two small molecule drugs targeting SAT1, namely Argatroban and Menadione, were predicted. Moreover, their therapeutic potentials in the treatment of UV-irradiated skin injury were confirmed experimentally.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114334"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508966","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}
Lianghe Wen , Zhen Quan , Chunming Guan , Junbo Zheng , Yunlong Li , Siyao Zeng , Zheng Han , Ming Ye , Hongliang Wang
{"title":"Targeted inhibition of NEK7 preventing sepsis-induced cardiomyopathy by inhibiting NLRP3 inflammasome","authors":"Lianghe Wen , Zhen Quan , Chunming Guan , Junbo Zheng , Yunlong Li , Siyao Zeng , Zheng Han , Ming Ye , Hongliang Wang","doi":"10.1016/j.intimp.2025.114245","DOIUrl":"10.1016/j.intimp.2025.114245","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis; however, its pathogenesis remains elusive. This study aims to investigate the role of NMA-related kinase 7 (NEK7) in SIC.</div></div><div><h3>Methods</h3><div>C57BL/6 mice were stimulated with lipopolysaccharide (LPS) to assess NEK7 expression in the myocardium. AAV-shNEK7 was administered to improve cardiac function and survival rates. HL-1 cardiomyocytes were treated with si-NEK7 after LPS stimulation, and cell viability was measured. Molecular docking analysis and co-immunoprecipitation assays were used to validate the interaction between NEK7 and the NLRP3 inflammasome.</div></div><div><h3>Results</h3><div>NEK7 was significantly upregulated in the myocardium of LPS-stimulated C57BL/6 mice. Administration of AAV-shNEK7 improved cardiac function and enhanced survival rates. In LPS-stimulated HL-1 cardiomyocytes, si-NEK7 treatment increased cell viability compared to control cells, due to the suppression of pyroptosis through attenuation of NLRP3 inflammasome activation. Molecular docking analysis and co-immunoprecipitation assays confirmed that targeting NEK7 inhibits its interaction with NLRP3, thereby suppressing inflammasome activation and providing a protective effect.</div></div><div><h3>Conclusions</h3><div>NEK7 plays a crucial role in SIC by facilitating NLRP3 inflammasome activation. Targeting NEK7 presents a potential therapeutic approach for SIC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114245"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488791","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}
Zhao Gao , Sushan Cao , Haiqing Yuan, Jim Zhen Wu, Gang Zou
{"title":"Broad antifibrotic activities of AK3280 in pulmonary, hepatic, cardiac, and skin fibrosis animal models","authors":"Zhao Gao , Sushan Cao , Haiqing Yuan, Jim Zhen Wu, Gang Zou","doi":"10.1016/j.intimp.2025.114337","DOIUrl":"10.1016/j.intimp.2025.114337","url":null,"abstract":"<div><div>Fibrosis is the pathological outcome of many chronic inflammatory diseases, affecting various human organs. It is a significant contributor to global morbidity and mortality that affects nearly half of the elderly population. Pirfenidone (PFD) and nintedanib are approved by the FDA for treating pulmonary fibrosis, but these treatments are associated with poor tolerability and limited efficacy. Moreover, no antifibrotic drugs are approved for other fibrosis-related diseases, highlighting an urgent unmet medical need for more effective therapies. Here we report the in vivo pharmacological activities of AK3280, a novel, orally bioavailable small molecule designed to enhance pharmacokinetics, antifibrotic activity, and tolerability over PFD. AK3280 demonstrated antifibrotic effects across multiple organs, including the lungs, liver, heart, and skin, in various animal models. These results suggest that AK3280 holds promise as a clinically beneficial antifibrotic therapy for a range of fibrotic diseases, especially pulmonary, hepatic, cardiac, and skin fibrosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114337"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488404","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":"Interleukin-36β inhibits CD4+CD25+ regulatory T cells by activating endoplasmic reticulum-phagy in septic mice","authors":"Yun Ge , Xi Chen","doi":"10.1016/j.intimp.2025.114349","DOIUrl":"10.1016/j.intimp.2025.114349","url":null,"abstract":"<div><h3>Background</h3><div>CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells (Tregs) contribute to the pathogenesis of sepsis-induced immunosuppression. We have identified interleukin (IL)-36β as a critical cytokine regulating CD4<sup>+</sup>CD25<sup>+</sup> Treg activity.</div></div><div><h3>Methods</h3><div>This study aimed to further investigate the underlying mechanism of IL-36β-triggered responses in murine CD4<sup>+</sup>CD25<sup>+</sup> Tregs in presence of lipolysaccharide (LPS) and in a mouse model of sepsis induced by cecal and puncture (CLP).</div></div><div><h3>Results</h3><div>Following LPS exposure, ER-phagy activity increased, peaked at 12 h, and then markedly declined. Furthermore, we observed that IL-36β could activate ER-phagy of CD4<sup>+</sup>CD25<sup>+</sup> Tregs under LPS challenge. Mechanistic investigations revealed the critical involvement of the endoplasmic reticulum (ER) stress-related protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4) signaling axis in IL-36β-induced ER-phagy. Moreover, IL-36β knockout (IL-36β<sup>−/−</sup>) strongly dampened ER-phagy and PERK-ATF4 signaling under LPS stimulation compared to the wild-type group. IL-36β-elicited effects on CD4<sup>+</sup>CD25<sup>+</sup> Tregs were significantly abrogated by FAM134B (the ER-phagy-specific receptor) knockout or salubrinal (a specific inhibitor of the PERK-ATF4 pathway). In addition, IL-36β was potent in diminishing serum levels of creatinine (Cr), aspartate transaminase (AST), and alanine transaminase (ALT) and attenuated histopathologic alterations in the liver, kidneys, and lungs of CLP mice. Importantly, the absence of IL-36β notably aggravated the survival rate of septic mice, indicating a beneficial role in septic prognosis.</div></div><div><h3>Conclusion</h3><div>IL-36β can down-regulate the immune activity of CD4<sup>+</sup>CD25<sup>+</sup> Tregs via ER-phagy induction. Our study might provide novel targets for therapeutic strategies to prevent the development of sepsis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114349"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The key role of natural products in the fight against endometrial Cancer","authors":"Wen Chen , Wencheng Zhou , Songjun Liu","doi":"10.1016/j.intimp.2025.114344","DOIUrl":"10.1016/j.intimp.2025.114344","url":null,"abstract":"<div><div>Endometrial cancer (EC) is a common malignant disease in women, originating from the endometrial tissue. Over the past few decades, the global incidence rate of EC has gradually increased, and the affected population has become progressively younger. Traditional treatment methods, such as surgery and adjuvant therapy, have considerable toxic side effects. Furthermore, their therapeutic effectiveness is significantly very uncertain. Therefore, the search for a new type of treatment for EC is a top priority. Natural products are a class of compounds found in nature that have a wide range of biological functions; their derivatives have chemical structures that show great potential for developing new drugs. The latest studies have found that certain natural products, such as flavonoids, plant polyphenols, terpenoids and alkaloids, have inhibitory effects on EC cells in non-clinical models and animal studies. Despite challenges, including low extraction and bioavail ability, the potential of natural products for treating EC is still highly regarded by the scientific community. In the future, as research on natural products deepens and is combined with modern drug design and delivery technologies, it is hoped that more efficient and less toxic anti-cancer drugs will be developed, thereby offering EC patients more treatment options and hope. This article summarises the possible molecular mechanisms of various natural products and their bioactive components with regard to EC cells, as well as the latest research, to provide new ideas for further research and drug development.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114344"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488403","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":"Prdx5 regulates macrophage polarization by modulating the TLR4/NF-κB pathway to promote apoptosis in chronic prostatitis","authors":"Weikang Wu , Tong Meng , Yufan Wang , Jing Chen, Chaozhao Liang","doi":"10.1016/j.intimp.2025.114332","DOIUrl":"10.1016/j.intimp.2025.114332","url":null,"abstract":"<div><div>Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urological disorder characterized by urinary symptoms, pelvic pain, and sexual dysfunction. Despite its high prevalence, the pathogenesis of CP/CPPS remains poorly understood. Our study revealed that peroxiredoxin 5 (Prdx5) was upregulated in M1 macrophages and in mice with experimental autoimmune prostatitis (EAP), with its expression in macrophages being regulated in a reactive oxygen species (ROS)-dependent manner. Using western blotting, RT-qPCR, immunohistochemical staining, hematoxylin and eosin staining, immunofluorescence staining, flow cytometry, and cell co-culturing, it was demonstrated that the silencing of Prdx5 suppressed the polarization of macrophages towards the M1 phenotype. This inhibition reduced apoptosis in prostate epithelial cells and mitigated the progression of EAP. Furthermore, Prdx5 mediated its effects in macrophages and EAP via the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway. Our findings suggest that Prdx5 promoted the occurrence and development of CP/CPPS due to its promotion of M1 polarization and apoptosis of prostate epithelial cells in an ROS-dependent manner via the TLR4/NF-κB axis, indicating its potential as a therapeutic target to treat CP/CPPS.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114332"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487979","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}
Shu-Yun Wei , Yu-Long Li , Lin Wang , Zi-Yong Chu , Yan-Chun Qin , Hong Zeng
{"title":"α-Pinene: Inhibitor of Acinetobacter baumannii biofilms and potential therapeutic agent for pneumonia","authors":"Shu-Yun Wei , Yu-Long Li , Lin Wang , Zi-Yong Chu , Yan-Chun Qin , Hong Zeng","doi":"10.1016/j.intimp.2025.114287","DOIUrl":"10.1016/j.intimp.2025.114287","url":null,"abstract":"<div><div><em>Acinetobacter baumannii</em> is a Gram-negative bacterium whose biofilm formation and mechanisms contribute to its persistent infectivity and drug resistance in clinical settings. Inhibition or disruption of biofilms might hold the key to resolving the issue of drug resistance in <em>A. baumannii</em>. α-Pinene, a bicyclic terpene olefin derived from the essential oils of plants, exhibits multiple biological activities, including antimicrobial, antioxidant, and anti-inflammatory effects. In this investigation, we discovered that α-Pinene had powerful antimicrobial activity against <em>A. baumannii</em> 390015, and its minimum inhibitory concentration was 0.625 μL/mL. <em>In vitro</em> experiments demonstrated that α-Pinene exerted an inhibitory effect on biofilm formation and impacted the production of extracellular polymers and the twitching motility of <em>A. baumannii</em>. Moreover, qRT-PCR experiments in combination with proteomic validation revealed that <em>bmfR</em>, <em>csuA</em>B, <em>ompA</em>, and <em>bap</em> were down-regulated in <em>A. baumannii</em> after the action of α-Pinene. <em>In vivo</em> experiments indicated that α-Pinene decreased the expression of inflammatory factors, including interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in tissues. Additionally, the expression levels of JNK, P38, and ERK in the downstream pathways of TRAF6 were evaluated, and it was found that α-Pinene decreased the expression levels of JNK, P38, and ERK. Notably, the expression levels of these markers increased as the concentration of α-Pinene decreased. These findings suggest that α-Pinene can inhibit biofilm formation in <em>A. baumannii</em> and mitigate inflammation, highlighting its therapeutic potential for <em>A. baumannii</em> infections.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114287"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488402","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}