Prostaglandins & other lipid mediators最新文献

{"title":"Prostanoid signaling in retinal vascular diseases","authors":"Amy K. Stark ,&nbsp;John S. Penn","doi":"10.1016/j.prostaglandins.2024.106864","DOIUrl":"10.1016/j.prostaglandins.2024.106864","url":null,"abstract":"<div><p>The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106864"},"PeriodicalIF":2.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1098882324000583/pdfft?md5=9c8bdd825d6d2460488ccb1f216bf9c4&pid=1-s2.0-S1098882324000583-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GOLPH3 knockdown alleviates the inflammation and apoptosis in lipopolysaccharide-induced acute lung injury by inhibiting Golgi stress mediated autophagy","authors":"Yanru Wang ,&nbsp;Xiaoxia Li ,&nbsp;Qin Zhou ,&nbsp;Su Zhang","doi":"10.1016/j.prostaglandins.2024.106865","DOIUrl":"10.1016/j.prostaglandins.2024.106865","url":null,"abstract":"<div><p>Pneumonia, an acute inflammatory lesion of the lung, is the leading cause of death in children aged &lt; 5 years. We aimed to study the function and mechanism of Golgi phosphoprotein 3 (GOLPH3) in infantile pneumonia. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and injury of MLE-12 cells were used as the pneumonia model in vitro. After GOLPH3 was knocked down, the histopathological changes of lung tissues were assessed by hematoxylin-eosin (H&amp;E) staining. The Wet/Dry ratio of lung tissues was calculated. The enzyme-linked immunosorbent assay (ELISA) method was used to detecte the contents of inflammatory factors in bronchoalveolar lavage fluid (BALF). The damaged DNA in apoptotic cells in lung tissues was tested by Terminal deoxynucleotidyl transferase-mediated dUTP Nick end labeling (TUNEL) staining. Immunofluorescence staining analyzed LC3II and Golgi matrix protein 130 (GM130) expression in lung tissues and MLE-12 cells. The apoptosis of MLE-12 cells was measured by flow cytometry analysis. Additionally, the expression of proteins related to apoptosis, autophagy and Golgi stress was examined with immunoblotting. Results indicated that GOLPH3 knockdown alleviated lung tissue pathological changes in LPS-triggered ALI mice. LPS-induced inflammation and apoptosis in lung tissues and MLE-12 cells were remarkably alleviated by GOLPH3 deficiency. Besides, GOLPH3 depletion suppressed autophagy and Golgi stress in lung tissues and MLE-12 cells challenged with LPS. Moreover, Rapamycin (Rap), an autophagy inhibitor, counteracted inflammation and apoptosis inhibited by GOLPH3 silencing in LPS-induced MLE-12 cells. Furthermore, brefeldin A (BFA) pretreatment apparently abrogated the inhibitory effect of GOLPH3 knockdown on autophagy in MLE-12 cells exposed to LPS. To be concluded, GOLPH3 knockdown exerted lung protective effect against LPS-triggered inflammation and apoptosis by inhibiting Golgi stress mediated autophagy.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106865"},"PeriodicalIF":2.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of curcumin supplementation on biomarkers of inflammation, oxidative stress, and endothelial function: A meta-analysis of meta-analyses","authors":"Zeynab Kavyani ,&nbsp;Kianoosh Najafi ,&nbsp;Navid Naghsh ,&nbsp;Houshang Bavandpour Karvane ,&nbsp;Vali Musazadeh","doi":"10.1016/j.prostaglandins.2024.106867","DOIUrl":"10.1016/j.prostaglandins.2024.106867","url":null,"abstract":"<div><p>Numerous interventional studies have revealed the beneficial impact of curcumin supplementation on inflammation, oxidative stress, and endothelial function biomarkers, but the findings are still inconsistent. Thus, this study was conducted to investigate the effects of curcumin supplementation on inflammation, oxidative stress, and endothelial function biomarkers. A meta-analyses of randomized clinical trials was performed by searching PubMed, Embase, Scopus, and Web of Science up to March 31, 2024. Pooled estimates of 21 meta-analyses revealed that curcumin significantly reduced CRP (weighted mean difference (WMD) = −0.87; 95 % CI: - 1.14, - 0.59, P&lt; 0.001), tumor-necrosis factor-alpha (TNF-α) (WMD = −2.72; 95 % CI: −4.05, −1.38; P&lt; 0.001), interleukin-6 (IL-6) (WMD = −0.97, 95 % CI: −1.40, −0.54; P&lt; 0.001), malondialdehyde (MDA) (Effect size (ES) = −0.81; 95 % CI: −1.39, −0.23, P = 0.006) and pulse wave velocity (PWV) (WMD = −45.60; 95 % CI: −88.16, −3.04, P = 0.036), and increased flow-mediated dilation (FMD) (WMD = 1.64, 95 % CI: 1.06, 2.22, P &lt; 0.001), catalase (CAT) (WMD = 10.26; 95 % CI: 0.92, 19.61, P= 0.03), glutathione peroxidase (GPx) (WMD = 8.90; 95 % CI: 6.62, 11.19, P &lt;0.001), and superoxide dismutase (SOD) levels (WMD = 20.51; 95 % CI: 7.35, 33.67, P= 0.002 and SMD = 0.82; 95 % CI: 0.27, 1.38, P= 0.004). However, curcumin did not significantly change total antioxidant capacity (TAC) (ES = 0.29; 95 % CI: −0.09, 0.66, P= 0.059). These results suggest that curcumin has a beneficial effect on CRP, IL-6, TNF-α, SOD, GPx, CAT, MDA, PWV, and FMD levels and may be an effective adjunctive therapy for improving inflammation, oxidative stress, and endothelial function. Registration number: PROSPERO, CRD42024539018.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106867"},"PeriodicalIF":2.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interference with GPR4 inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate oxygen-glucose deprivation/reoxygenation-induced inflammation and apoptosis of cardiomyocytes","authors":"Hanlong He ,&nbsp;Huiren Su ,&nbsp;Xinjian Chen ,&nbsp;Xiaohong Chen ,&nbsp;Shaoze Yang","doi":"10.1016/j.prostaglandins.2024.106863","DOIUrl":"10.1016/j.prostaglandins.2024.106863","url":null,"abstract":"<div><p>Myocardial ischemia/reperfusion (MI/R) injury is a detrimental disease with high mortality worldwide. We aimed to explore the role of G protein-coupled receptor 4 (GPR4) and lysophosphatidic acid receptor 1 (LPAR1) in MI/R injury in vitro. H9c2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to simulate the MI/R injury and GPR4 expression was detected. Then, GPR4 was knocked down and cell viability was examined with a CCK-8 assay. The activities of LDH, CK and CK-MB were detected to evaluate the damage of OGD/R-induced H9c2 cells. ELISA kits and TUNEL staining were used to examine the inflammation and apoptosis of H9c2 cells exposed to OGD/R conditions. Western blot was employed to detect the expression of proteins related to apoptosis and NLRP3 inflammasome signaling. Additionally, Co-IP analyzed the binding between GPR4 and LPAR1. Finally, LPAR1 was overexpressed to conduct the rescue experiments. Results revealed that GPR4 was upregulated in OGD/R-treated H9c2 cells and GPR4 knockdown attenuated the damage of H9c2 cells. OGD/R induced inflammation and apoptosis were markedly inhibited by GPR4 silencing, as evidenced by the decreased TNF-α, IL-6 and IL-8 levels as well as the elevated Bcl-2 expression and reduced Bax and cleaved caspase3 expression. Moreover, GPR4 bound to LPAR1 and upregulated LPAR1 expression. Interference with GPR4 inactivated the NLRP3 inflammasome signaling. Besides, LPAR1 overexpression abrogated the effects of GPR4 silencing on the damage, inflammation and apoptosis of H9c2 cells induced by OGD/R. Particularly, LPAR1 upregulation promoted the activation of NLRP3 inflammasome signaling in GPR4-silenced H9c2 cells induced by OGD/R. To be concluded, GPR4 deficiency inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate OGD/R -induced inflammation and apoptosis of cardiomyocytes.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106863"},"PeriodicalIF":2.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sesame oil downregulates the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis","authors":"S.S. Aswani ,&nbsp;N.S. Aparna ,&nbsp;Mithra S. Mohan ,&nbsp;P.T. Boban ,&nbsp;K. Saja","doi":"10.1016/j.prostaglandins.2024.106862","DOIUrl":"10.1016/j.prostaglandins.2024.106862","url":null,"abstract":"<div><p>Atherosclerosis is a chronic inflammatory disease forming plaques in medium and large-sized arteries. ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) is an extracellular-matrix remodelling enzyme involved in the degradation of versican in the arterial wall. Recent reports indicated that increased expression of ADAMTS-4 is associated with plaque progression and vulnerability. Bioactive components of dietary oil, like sesame oil, are reported to have anti-inflammatory and antioxidant properties. Here, we studied the effect of sesame oil on regulating ADAMTS-4 in high-fat diet-induced atherosclerosis rat model. Our results indicated that sesame oil supplementation improved the anti-inflammatory and anti-oxidative status of the body. It also reduced atherosclerotic plaque formation in high-fat diet-fed rats. Our results showed that the sesame oil supplementation significantly down-regulated the expression of ADAMTS-4 in serum and aortic samples. The versican, the large proteoglycan substrate of ADAMTS-4 in the aorta, was downregulated to normal control level on sesame oil supplementation. This study, for the first time, reveals that sesame oil could down-regulate the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis, imparting a new therapeutic potential for sesame oil in the management of atherosclerosis.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106862"},"PeriodicalIF":2.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel anti-cancer effect of 2-arachidonoylglycerol via processing body formation in HCA-7 human colon cancer cells","authors":"Takaya Misao,&nbsp;Keijo Fukushima,&nbsp;Hiromichi Fujino","doi":"10.1016/j.prostaglandins.2024.106861","DOIUrl":"10.1016/j.prostaglandins.2024.106861","url":null,"abstract":"<div><p>The endocannabinoid 2-arachidonoylglycerol (2-AG) has been reported to exhibit anticancer effects, including against colorectal cancer (CRC); however, the detailed mechanisms have not been clarified. Herein, we demonstrated that 2-AG suppressed cyclooxygenase-2 (COX-2) expression induced by prostaglandin E₂ in human colon cancer HCA-7 cells. The suppression of COX-2 expression by 2-AG was through the acceleration of processing body (P-body) formation followed by COX-2 mRNA degradation. These effects were restored by TAK-715, a specific inhibitor of p38 MAPK. Therefore, the effect of 2-AG on COX-2 may be distinct from conventional non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit the function of COX-2, whereas 2-AG suppresses the protein expression of COX-2. Recently, the cardiovascular risks of NSAIDs were reported by the Food and Drug Administration in the United States. Therefore, elucidation of the effect of 2-AG is expected to contribute to the development of an alternative and novel therapeutic option that would have no or fewer risks regarding cardiovascular events.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106861"},"PeriodicalIF":2.5,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of curcumin on paraoxonase 1 protein levels, gene expression, and enzyme activity: A systematic review of animal interventional studies","authors":"Fatemeh Hamedi-Kalajahi ,&nbsp;Mohammad Alizadeh ,&nbsp;Sorayya Kheirouri ,&nbsp;Roghayeh Molani-Gol","doi":"10.1016/j.prostaglandins.2024.106849","DOIUrl":"10.1016/j.prostaglandins.2024.106849","url":null,"abstract":"<div><h3>Background and aims</h3><p>Paraoxonase (PON) proteins have various hydrolytic activities. The PON family is able to detoxify oxidized low-density lipoprotein. Additionally, differentiation of monocytes into macrophages, as the first stage in the development of atherosclerosis, is suppressed by PON 1. The effects of polyphenols including curcumin on PON1 have been investigated in studies. In this study, our main goal is to investigate curcumin’s effect on PON1 protein levels, gene expression, and enzyme activity in animal interventional studies.</p></div><div><h3>Methods</h3><p>The literature was searched through the online databases including PubMed, SCOPUS, Embase, and Google Scholar until May 2022.</p></div><div><h3>Results</h3><p>Curcumin administration can increase the PON1 enzyme activity. Also, it probably has a positive role in increasing the PON1 gene expression. However, concerning the PON1 protein values, results are contradictory.</p></div><div><h3>Conclusions</h3><p>The findings of this study suggested positive role of curcumin in increasing PON1 enzyme activities, gene expression, and protein levels.</p></div><div><h3>Data Availability</h3><p>Data are available from the corresponding author (<span><span>[email protected]</span></span><svg><path></path></svg>)</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106849"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways","authors":"Genesee J. Martinez ,&nbsp;Zachary A. Kipp ,&nbsp;Wang-Hsin Lee ,&nbsp;Evelyn A. Bates ,&nbsp;Andrew J. Morris ,&nbsp;Joseph S. Marino ,&nbsp;Terry D. Hinds Jr.","doi":"10.1016/j.prostaglandins.2024.106840","DOIUrl":"10.1016/j.prostaglandins.2024.106840","url":null,"abstract":"<div><p>We have previously demonstrated that the glucocorticoid receptor β (GRβ) isoform induces hepatic steatosis in mice fed a normal chow diet. The GRβ isoform inhibits the glucocorticoid-binding isoform GRα, reducing responsiveness and inducing glucocorticoid resistance. We hypothesized that GRβ regulates lipids that cause metabolic dysfunction. To determine the effect of GRβ on hepatic lipid classes and molecular species, we overexpressed GRβ (GRβ-Ad) and vector (Vec-Ad) using adenovirus delivery, as we previously described. We fed the mice a normal chow diet for 5 days and harvested the livers. We utilized liquid chromatography-mass spectrometry (LC-MS) analyses of the livers to determine the lipid species driven by GRβ. The most significant changes in the lipidome were monoacylglycerides and cholesterol esters. There was also increased gene expression in the GRβ-Ad mice for lipogenesis, eicosanoid synthesis, and inflammatory pathways. These indicate that GRβ-induced glucocorticoid resistance may drive hepatic fat accumulation, providing new therapeutic advantages.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"173 ","pages":"Article 106840"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EPA, DHA, and resolvin effects on cancer risk: The underexplored mechanisms","authors":"Yoshiyuki Kiyasu ,&nbsp;Xiangsheng Zuo ,&nbsp;Yi Liu ,&nbsp;James C. Yao ,&nbsp;Imad Shureiqi","doi":"10.1016/j.prostaglandins.2024.106854","DOIUrl":"10.1016/j.prostaglandins.2024.106854","url":null,"abstract":"<div><p>Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements have exhibited inconsistent effects on cancer risk, and their potential efficacy as cancer preventive agents has been increasingly questioned, especially in recent large randomized clinical trials. The role of host factors that govern EPA and DHA metabolism in relation to their impact on carcinogenesis remains understudied. Resolvins, the products of EPA and DHA oxidative metabolism, demonstrate intriguing antitumorigenic effects through mechanisms such as promoting macrophage phagocytosis of cell debris and inhibiting the production of proinflammatory chemokines and cytokines by tumor–associated macrophages (TAMs), which are crucial for cancer progression. However, clinical studies have not yet shown a significant increase in target tissue levels of resolvins with EPA and DHA supplementation. 15-Lipoxygenase-1 (ALOX15), a key enzyme in EPA and DHA oxidative metabolism, is often lost in various major human cancers, including precancerous and advanced colorectal cancers. Further research is needed to elucidate whether the loss of ALOX15 expression in colorectal precancerous and cancerous cells affects EPA and DHA oxidative metabolism, the formation of resolvins, and subsequently carcinogenesis. The findings from these studies could aid in the development of novel and effective chemoprevention interventions to reduce cancer risk.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106854"},"PeriodicalIF":2.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zerumbone exhibits anti-inflammatory effects by suppressing eicosanoid signaling: Evidence from LPS-induced peripheral blood leukocytes","authors":"Vinayak Uppin ,&nbsp;Mehrdad Zarei ,&nbsp;Pooja Acharya ,&nbsp;Devika Nair ,&nbsp;Bettadaiah Kempaiah ,&nbsp;Ramaprasad Talahalli","doi":"10.1016/j.prostaglandins.2024.106852","DOIUrl":"10.1016/j.prostaglandins.2024.106852","url":null,"abstract":"<div><p>Zerumbone, a sesquiterpene isolated from Zingiber zerumbet, has many bioactivities, exhibiting anti-inflammatory properties. However, the effect of zerumbone on the eicosanoid signaling pathway has yet to be examined. Here, we deciphered the anti-eicosanoid properties of zerumbone isolated from ginger. The molecular interaction between zerumbone and eicosanoid metabolizing enzymes (COX-2, 5-LOX, FLAP, and LTA₄-hydrolase) and receptors (EP-4, BLT-1, and ICAM-1) along with NOS-2 were assessed using Auto-Dock 4.2 and visualized by chimera and Liggplot⁺ software. Further, the leukocytes were treated with zerumbone (1–20 μM) and activated using bacterial lipopolysaccharide (LPS-10 nM). The oxidative stress (OS) markers, antioxidant enzymes, and the eicosanoid pathway mediators such as COX-2, 5-LOX, BLT-1, and EP-4 were assessed. The molecular interaction of zerumbone with eicosanoids showed a higher binding affinity with mPGES-1, followed by NOS-2, FLAP, COX-2, LTA-4-hydrolase, and BLT-1. The concentration of 5 μM zerumbone effectively prevented the generation of reactive oxygen species (ROS) and nitric oxide (NO). Likewise, zerumbone significantly (p&lt;0.05) inhibited COX-2, 5-LOX, NOS-2, EP-4, BLT-1, and ICAM-1 expression in LPS-induced peripheral blood leukocytes from rats. Further, the zerumbone treatment on the human PBMCs activated with LPS showed significant inhibition in the expression of ICAM1, COX-2, 5-LOX, and the generation of inflammatory cytokines compared to the control. Overall, the data presented infers that zerumbone positively modulates critical enzymes and receptors of eicosanoids in leukocytes activated with lipopolysaccharides. Thus, zerumbone can be a potential anti-eicosanoid drug in managing inflammation.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"173 ","pages":"Article 106852"},"PeriodicalIF":2.9,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}