Current molecular pharmacology最新文献

{"title":"RIPK1/RIPK3/MLKL Necrosome Contributes to the Sepsis-Induced Cardiorenal Necroptotic Inflammatory Injury and Mortality.","authors":"Bahar Tunctan, Muhammed Ahmed-Reda Elosman, Sefika Pinar Senol, Elif Ikiz, Tuba Kara","doi":"10.2174/0118761429374574250415114715","DOIUrl":"https://doi.org/10.2174/0118761429374574250415114715","url":null,"abstract":"<p><strong>Introduction: </strong>Due to its critical role in inflammation and necroptotic cell death, RIPK1 has been considered a prominent therapeutic drug target for managing a wide variety of diseases, including sepsis. Therefore, we aimed to investigate whether the RIPK1-driven necroptotic pathway contributes to the nitrosative stress-mediated cardiorenal inflammatory necroptotic injury and mortality using RIPK1 inhibitor, Nec-1s, in the murine sepsis model induced by LPS.</p><p><strong>Methods: </strong>Experiments were performed using mice injected intraperitoneally with DMSO or Nec-1s with saline and/or LPS. Following euthanasia and 6 hours after the injection of these agents, arteriovenous blood samples, hearts, and kidneys of the animals were collected. Serum MPO, iNOS, CKMB, creatinine, and HMGB1 levels were measured by ELISA. Associated proteins were measured by immunoblotting. H&E staining was used to evaluate histopathological changes in the tissues. In the mortality studies, the mice were monitored every 6 hours for mortality up to 96 hours after saline, LPS, DMSO, and/or Nec-1s injection.</p><p><strong>Results: </strong>In the LPS-injected mice, a rise in serum MPO, iNOS, CK-MB, creatinine, and HMGB1 levels was associated with the enhanced expression/activity of RIPK1/RIPK3/MLKL necrosome, HMGB1, iNOS, nitrotyrosine, gp91^phox, and p47^phox, in addition to scores related to histopathological changes in their tissues. Nec-1s attenuated the LPS-induced changes. Mortality rates of 10%, 50%, and 60% were observed at the 24^th, 36^th, and 48^th hours, respectively, in the LPS-treated mice. When endotoxemic mice were treated with Nec-1s, mortality rates were 60%, 90%, and 100% at 18, 30, and 42 hours, respectively.</p><p><strong>Conclusion: </strong>These findings suggest that RIPK1/RIPK3/MLKL necrosome contributes to not only LPS-induced nitrosative stress-mediated cardiorenal inflammatory necroptotic injury, but also mortality.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Isorhamnetin: Targeting MAPK and NF-κB Pathways to Mitigate LPS-Induced Inflammation.","authors":"Abdelrahim Alqudah, Muna Barakat, Lujain F Alzaghari, Esam Qnais, Omar Gammoh, Mohammad Alqudah, Alaa Aa Aljabali, Sireen Abdul Rahim Shilbayeh","doi":"10.2174/0118761429385248250409060550","DOIUrl":"https://doi.org/10.2174/0118761429385248250409060550","url":null,"abstract":"<p><p>Introduction Chronic inflammation may result in mucosal damage, presenting as pain, edema, convulsions, and fever symptoms. This study investigated the anti-inflammatory characteristics of isorhamnetin (ISO) and its potential as a medicinal agent. Method In this study, in vitro tests were performed in which macrophages were activated with lipopolysaccharide (LPS) to evaluate the effect of ISO on inflammation. We concentrated on quantifying the synthesis of pro-inflammatory cytokines, interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF-α], as well as mediators, such as nitric oxide [NO] and prostaglandin E2 [PGE2], in LPS-stimulated RAW 264.7 cells. Results The findings indicated that ISO significantly decreased levels of NO and PGE2 while maintaining cellular integrity. ISO reduced the synthesis of pro-inflammatory cytokines in a dose-dependent manner. Moreover, ISO treatment decreased mRNA levels of inducible nitric oxide synthase [iNOS] and cyclooxygenase-2 [COX-2], which were enhanced following LPS exposure. Mechanistic investigations revealed that the antiinflammatory properties of ISO were facilitated by the inhibition of phosphorylation in the mitogen-activated protein kinase [MAPK] family and the downregulation of nuclear factor-kappa B inhibitor [IκB-α] within both the MAPK and nuclear factor-kappa B [NF-κB] pathways. Conclusion These findings establish ISO as a viable alternative for treating inflammatory diseases by specifically inhibiting essential inflammatory pathways.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of miRNAs in Podocyte Injury in Diabetic Nephropathy: Mechanisms and Clinical Applications.","authors":"Shan Hu, Jiafu Yan, Qiong Yuan, Tianjiao Meng, Zhi Cai, Yuanshuai Huang, Yuhan Wang","doi":"10.2174/0118761429363169250313083148","DOIUrl":"https://doi.org/10.2174/0118761429363169250313083148","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the most frequent complications of diabetes and, if left uncontrolled, can progress to renal failure. In the early stage of DKD, significant pathological changes occur in podocytes, leading to proteinuria. However, the mechanism of pathological changes in podocytes has not been clarified. Existing clinical diagnostic methods tend to overlook these subtle pathophysiological changes in the early stages, leading to missed optimal treatment time. Moreover, existing treatment methods are limited. Emerging evidence strongly suggests that podocyte injury is associated with distinct specific miRNA expression profiles that precede the onset of overt proteinuria and glomerular filtration rate decline. This review explores the role of microRNAs in podocyte damage-related pathways in DKD, such as reactive oxygen species (ROS) production and inflammatory responses. Furthermore, we discuss the potential clinical application of miRNAs as molecular markers and their feasibility as a molecular therapy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Complement Component 3 (C3) in Psoriasis.","authors":"Qiong Cao, Junqin Li, Kaiming Zhang","doi":"10.2174/0118761429361884250318071733","DOIUrl":"https://doi.org/10.2174/0118761429361884250318071733","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory disease driven by immune dysfunction, with its pathogenesis still not fully understood. This article explores the crucial roles of complement molecules in psoriasis, emphasizing complement C3's pathogenic mechanisms and its potential as a therapeutic target. The complement system's structure and function highlight its significance in immune response and inflammation regulation. This system is activated through the classical, alternative, and lectin pathways, with complement C3, primarily produced by hepatocytes and macrophages, serving as a core component and the most abundant complement in serum. The article analyzes C3's structure and biological functions to reveal its pathogenic roles in psoriasis, detailing its specific mechanisms in immune abnormalities and skin lesions as supported by recent studies. The activation of the complement system leads to C3 convertase formation, cleaving C3 into C3a and C3b. T cells, though expressing lower C3 levels, produce C3a and C3b, regulating vital T cell functions like CD4+ T cell differentiation and survival. The review also summarizes current therapeutic strategies targeting C3, evaluating their potential effectiveness in alleviating psoriasis symptoms. C3aR inhibitors, such as SB290157, can slow disease progression, proposing a novel therapeutic approach for psoriasis. This comprehensive review offers new insights and theoretical foundations for complement C3 as a target for psoriasis treatment, aiming to advance future research and clinical interventions.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of miR-3130-5p Enhances Hepatocellular Carcinoma Growth by Suppressing Ferredoxin 1 : miR-3130-5p Enhances HCC Growth via Inhibiting FDX1.","authors":"Wanwen Xu, Shengbo Liao, Ying Hu, Yinghui Huang, Jie Zhou","doi":"10.2174/0118761429358008250305070518","DOIUrl":"https://doi.org/10.2174/0118761429358008250305070518","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma [HCC] is a leading cause of cancer-related mortality worldwide, necessitating the exploration of novel therapeutic targets. Although accumulating studies have identified Ferredoxin 1 [FDX1], a key regulator of cuproptosis, as a candidate tumor suppressor and potential therapeutic target, its role and mechanism remain elusive in HCC.</p><p><strong>Methods: </strong>The FDX1 expression was investigated in human HCC tissues and cell lines. Potential microRNAs targeting FDX1 were predicted by bioinformatic analysis and validated using qPCR screening, a dual luciferase reporter assay, MiR-3130-5p and miR-1910-3p mimics and inhibitors, overexpression plasmids, and xenograft nude mouse model. The correlation between miR-3130-5p/FDX1 axis and HCC patient prognosis was analyzed by using Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>We demonstrated that the expression of FDX1 was downregulated in human HCC tissues and cell lines compared to non-cancerous counterparts, and the downregulation of FDX1 was associated with poor overall survival in HCC patients. Subsequent bioinformatic analysis and experimental validations showed that FDX1 expression was reduced by microRNA [miR]-3130-5p mimic while induced by miR-3130-5p inhibitor. Further, miR-3130-5p was upregulated in HCC tissues and cells, correlating with a poor prognosis of HCC patients. Besides, lentivirus-mediated overexpression of miR-3130-5p significantly enhanced HCC growth in xenograft nude mouse models. Mechanistically, it was demonstrated that miR-3130-5p inhibited FDX1 expression via binding to its 3' untranslated region [3' UTR], while overexpression of FDX1 counteracted the promoting effect of miR-3130-5p on HCC cell proliferation.</p><p><strong>Conclusion: </strong>These findings suggest the miR-3130-5p/FDX1 axis as a prognostic biomarker as well as a potential therapeutic target in HCC.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin Mitigates High Glucose-Disrupted Mitochondrial Respiratory Function in H9c2 Cardiomyoblasts: A Comparative Study with NHE-1 and ROCK Inhibition.","authors":"Cheng-I Cheng, Ming-Huei Chou, I-Ling Shih, Po-Han Chen, Ying-Hsien Kao","doi":"10.2174/0118761429360640250227054103","DOIUrl":"https://doi.org/10.2174/0118761429360640250227054103","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia in patients with Diabetes Mellitus (DM) increases the risk of developing cardiomyopathy and heart failure. Elevation of sodium/proton exchanger-1 (NHE-1) expression and activity in cardiomyocytes leads to greater sensitivity to neurohormonal stimulation and cardiomyopathy, whereas inhibition of Sodium-Glucose Cotransporter 2 (SGLT2) clinically benefits DM population in reducing heart failure risk.</p><p><strong>Aims: </strong>This study characterized the expression profiles of NHE-1 and SGLT2 in H9c2 cardiomyoblasts under High Glucose (HG) exposure and examined the effects of Empagliflozin (EMPA), an SGLT2 inhibitor, on the HG-induced cardiomyoblasts deterioration, in comparison with NHE-1 specific inhibitor cariporide and Rho/ROCK inhibitor hydroxy fasudil.</p><p><strong>Methods: </strong>Western blotting and immunofluorescent staining were used to monitor protein expression and subcellular location, respectively. Reactive Oxygen Species (ROS) production and mitochondrial membrane potential were measured by flow cytometry. Kinetic mitochondrial oxygen consumption rate and respiratory function were monitored by a real-time cell metabolic analyzer.</p><p><strong>Results: </strong>HG treatment upregulated SGLT2 and NHE-1 expression and RhoA/ROCK activity in H9c2 cardiomyoblasts. The HG-upregulated NHE-1 is localized in actin-rich cortical cytoplasm, implicating its involvement in cell shape and adhesion alterations. Treatment with NHE-1 and ROCK inhibitors, but not EMPA, significantly attenuated the HG-induced ROS overproduction and mitochondrial membrane potential elevation. However, EMPA treatment restored the HG-suppressed mitochondrial maximal respiration, spare respiratory capacity, and non-mitochondrial oxygen consumption rate.</p><p><strong>Conclusion: </strong>In comparison, Rho/ROCK and NHE-1 inhibitions effectively prevent ROS overproduction, while SGLT2 inhibition rescues the deteriorated mitochondrial respiratory function under diabetogenic conditions. Blockade of SGLT2, NHE-1, or Rho/ROCK activity is useful for the prevention of diabetic cardiomyopathy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Immune-Related Molecular Mechanisms Underlying the Comorbidity of Temporal Lobe Epilepsy and Major Depressive Disorder through Integrated Data Set Analysis.","authors":"Shi Yan, Zhibin Han, Tianyu Wang, Aowen Wang, Feng Liu, Shengkun Yu, Lin Xu, Hong Shen, Li Liu, Zhiguo Lin, Meng Na","doi":"10.2174/0118761429380394250217093030","DOIUrl":"https://doi.org/10.2174/0118761429380394250217093030","url":null,"abstract":"<p><strong>Background: </strong>Temporal lobe epilepsy (TLE) and major depressive disorder (MDD) are prevalent and complex neurological disorders that affect individuals globally. Clinical and epidemiological studies indicate a significant comorbidity between TLE and MDD; however, the shared molecular mechanisms underlying this relationship remain unclear. This study aims to explore the common key genes associated with TLE and MDD through a systematic analysis of gene expression profiles, elucidate their underlying molecular pathological mechanisms, and evaluate the potential applications of these genes in diagnostic and therapeutic contexts.</p><p><strong>Methods: </strong>Brain tissue gene expression data for TLE and MDD were obtained from the GEO database. Differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), functional enrichment, and protein-protein interaction (PPI) network construction were performed to identify shared gene modules. LASSO and random forest (RF) machine learning models were used to select diagnostic candidate genes, validated through ROC curve analysis. Immune infiltration analysis explored the immune involvement of key genes, while single-cell sequencing confirmed gene expression across cell types. Potential therapeutic drugs were identified using a drug database.</p><p><strong>Results: </strong>A total of 372 DEGs were identified as either up- or down-regulated between TLE and MDD, with WGCNA revealing nine shared gene modules. Seven hub genes, including HTR7 and CDHR2, demonstrated strong ROC performance. Immune infiltration analysis revealed changes in immune cell populations linked to key genes, confirmed by single-cell sequencing. Upadacitinib was identified as a potential therapeutic drug targeting these genes.</p><p><strong>Conclusion: </strong>This study identified shared gene expression profiles between TLE and MDD, emphasizing immune pathway-related molecular mechanisms. Immune infiltration analysis and single-cell sequencing underscored the significance of immune regulation in their comorbidity, while drug prediction highlights candidates for precision medicine, establishing a foundation for future research and therapeutic strategies.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two GnRH-mitoxantrone Conjugates, Con-3 and Con-7, Target Endometrial Cancer Cells.","authors":"Christos Markatos, Georgia Biniari, Vlasios Karageorgos, Oleg G Chepurny, Maria Venihaki, George G Holz, Theodore Tselios, George Liapakis","doi":"10.2174/0118761429343090250121052955","DOIUrl":"https://doi.org/10.2174/0118761429343090250121052955","url":null,"abstract":"<p><strong>Introduction: </strong>Endometrial cancer is one of the most common gynecological malignancies. Endometrial cancer cells express the gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R). Among the various therapeutic approaches for the treatment of endometrial cancer is the use of GnRH conjugates, such as the AN-152, created by linking the [D-Lys6] GnRH with the cytotoxic doxorubicin through an ester bond. An undesirable property of these conjugates is their vulnerability to plasma carboxylesterases, which cleave the ester bond to release doxorubicin before reaching the cancer cells.</p><p><strong>Methods: </strong>To overcome this problem, we recently developed the Con-3 and Con-7, which are GnRH analogs conjugated through a disulfide bond with the cytotoxic mitoxantrone. In this study, we determined the cytotoxic properties of the Con-3 and Con-7 on the Ishikawa endometrial cancer cells, assuming that their interaction with the GnRH-R of cells exposes the conjugated mitoxantrone to the cellular thioredoxin. The cellular thioredoxin reduces the disulfide bond of Con-3 & Con-7 to release mitoxantrone, which accumulates in the cancer cells and exerts its cytotoxic actions.</p><p><strong>Results: </strong>Indeed, treatment of Ishikawa cells with Con-3, Con-7, or the free unconjugated mitoxantrone increased their apoptosis and decreased their proliferation in a dose- and time-dependent manner, displaying half-maximal inhibitory concentrations (IC50) of 0.64 - 1.15 μM. In specific, the IC50 values on days 2, 3, and 4 were 1.45, 0.64, and 0.83 μΜ, respectively, for Con-3, 0.91, 0.82 μΜ, and 1.00 μΜ, respectively for Con-7 and 1.15, 0.98, 0.78 μM, respectively for mitoxantrone.</p><p><strong>Conclusion: </strong>In contrast, the free, mitoxantrone-unconjugated peptides did not affect the proliferation of Ishikawa cells. The Con-3 and Con-7 could put the basis for the development of a new class of anticancer drugs for endometrial cancer, which will act as \"prodrugs\" that deliver the cytotoxic mitoxantrone in a GnRH-R-specific manner.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirt1 Regulates Phenotypic Transformation of Diabetic Cardiac Fibroblasts through Akt/Α-SMA Pathway.","authors":"Xiaomei Li, Shimeng Huang, Yuanbo Gao, Ying Wang, Siyu Zhao, Bing Lu, Aibin Tao","doi":"10.2174/0118761429353519250106115016","DOIUrl":"10.2174/0118761429353519250106115016","url":null,"abstract":"<p><strong>Aims: </strong>Cardiac fibrosis causes most pathological alterations of cardiomyopathy in diabetes and heart failure patients. The activation and transformation of cardiac fibroblasts (CFs) are the main pathological mechanisms of cardiac fibrosis. It has been established that Sirtuin1 (Sirt1) plays a protective role in the pathogenesis of cardiovascular disorders. This study aimed to ascertain the Sirt1 effect on the phenotypic transformation of CFs in diabetes and its possible mechanisms.</p><p><strong>Methods: </strong>Type 1 diabetes was induced in 6-week-old male mice by subcutaneously injecting 50 mg/kg streptozotocin (STZ, i.p.). Western blotting, collagen staining, and echocardiography were performed to detect protein expression and assess cardiac fibrosis and function in vivo. We used high glucose (HG) to culture CFs prior to protein expression measurement in vitro.</p><p><strong>Results: </strong>Upregulation of Sirt1 expression effectively alleviated the degree of cardiac fibrosis by improving cardiac function in diabetic mice. In vitro experiments revealed that HG decreased the protein expression levels of Sirt1, but increased those of type I collagen and alpha-smooth muscle actin (α-SMA), as well as the transdifferentiation of fibroblasts into myofibroblasts. Further studies confirmed that downregulation of Sirt1 expression in the HG environment reduced the protein kinase-B (Akt) phosphorylation, thereby promoting the transdifferentiation of CFs into myofibroblasts coupled with the deterioration of cardiac function.</p><p><strong>Conclusion: </strong>Diabetes mellitus leads to downregulation of Sirt1 protein expression in CFs and decreased Akt phosphorylation, which promotes the transdifferentiation of CFs into myofibroblasts, the pathological process of cardiac fibrosis, and mediates the incidence and development of diabetic cardiomyopathy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of Platycodin D on Allergic Rhinitis in Mice through DPP4/JAK2/STAT3 Pathway Inhibition.","authors":"Qiao-Jing Jia, Zhichang Liu, Caixia Wang, Bingyi Yang, Xiangjian Zhang, Chunguang Shan, Jianxing Wang","doi":"10.2174/0118761429345310241211105707","DOIUrl":"https://doi.org/10.2174/0118761429345310241211105707","url":null,"abstract":"<p><strong>Background: </strong>Allergic Rhinitis (AR) is an inflammatory condition characterized by nasal mucosa remodeling, driven by Immunoglobulin E (IgE). Platycodin D (PLD) exhibits a wide range of bioactive properties.</p><p><strong>Aim: </strong>The aim of this work was to investigate the potential protective effects of PLD on AR, as well as the underlying mechanisms.</p><p><strong>Methods: </strong>The anti-allergic and anti-inflammatory potential of PLD was investigated in an ovalbumin-sensitized AR mouse model and human nasal mucosa cells (HNEpC) challenged with interleukin-13 combined with PLD. Our assessment included an examination of nasal symptoms, tissue pathology, and goblet cell hyperplasia. The levels of IgE, Interferon-gamma (IFN-γ), and interleukin-4 in the serum were detected using Enzyme-linked Immunosorbent Assay (ELISA). Furthermore, quantitative Real-time Polymerase Chain Reaction (RT-PCR) and ELISA were employed to determine the expressions of IL-1β, Tumor Necrosis Factor-alpha (TNF-α), and IL-6 in in vivo and in vitro settings. Western blot analysis was conducted to investigate the changes in DPP4/JAK2/STAT3 in vivo and in vitro.</p><p><strong>Results: </strong>Our results demonstrated that oral administration of PLD significantly ameliorated nasal symptoms in AR mice, improved histopathological changes in the nasal mucosa, raised the level of IFN-γ, and reduced IgE as well as IL-4 levels in the serum. PLD inhibited the expressions of IL-1β, IL-6, TNF-α, and DPP4 in in vivo and in vitro settings. Notably, PLD modulated the changes in DPP4, p-JAK2, and p-STAT3 induced by IL-13 in HNEpC cells and AR mice.</p><p><strong>Conclusion: </strong>The findings suggested the potential of PLD as a therapeutic agent for the treatment of AR.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}