Korean Journal of Physiology & Pharmacology最新文献

{"title":"Identification of common genetic features and pathways for osteoporosis with frozen shoulder by integrated bioinformatics analysis and machine learning.","authors":"Xiaofeng Yu, Zhenyu Ma, Lu Jin","doi":"10.4196/kjpp.25.259","DOIUrl":"10.4196/kjpp.25.259","url":null,"abstract":"<p><p>Frozen shoulder (FS) and osteoporosis (OP) are common age-related degenerative diseases, occurring more frequently in females, which suggests potential molecular links between them. This study aimed to identify shared genetic features and pathways of OP and FS using bioinformatics and machine learning approaches. Gene expression data for OP and FS were obtained from the Gene Expression Omnibus database. Common differentially expressed genes (DEGs) were identified. Functional enrichment analysis, protein-protein interaction (PPI) networks construction, and machine learning algorithms were applied to screen key genes. Diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. Immune infiltration and regulatory networks involving transcription factors and miRNAs were explored. Potential therapeutic compounds were also predicted. A total of 111 common DEGs were identified, enriched in pathways related to neurological development, cellular signaling, and immune regulation. PPI analysis revealed 14 hub genes, with SDC1 and ELN identified as key diagnostic markers by machine learning. ROC curves confirmed their diagnostic efficacy for both OP and FS. Immune infiltration analysis revealed distinct immune cell patterns in OP, correlating with the expression of key gene. Regulatory network analysis demonstrated complex transcriptional regulation of SDC1 and ELN. Drug prediction identified five candidate small molecules targeting these genes. This study uncovered shared genetic features of FS and OP through comprehensive bioinformatics analysis, enhancing understanding of their co-morbidity mechanisms. These findings provide a theoretical basis for identifying novel diagnostic biomarkers and therapeutic targets, facilitating the development of precise diagnostic strategies for OP with FS.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"125-138"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA KCNQ1OT1 aggravates myocardial ischemia/reperfusion injury by mediating the EZH2/TIMP-3 axis.","authors":"Zhi Xing, Abudureyimu Shajidan, Abulaiti Palida, Yu Wang, Maolin Lv, Ying Gao","doi":"10.4196/kjpp.25.148","DOIUrl":"10.4196/kjpp.25.148","url":null,"abstract":"<p><p>This study focused on discussing the mechanism of lncRNA KCNQ1OT1 mediating histone methylase enhancer of zeste homolog 2 (EZH2) to repress tissue inhibitor of metalloproteinase-3 (TIMP-3) expression in myocardial ischemia/reperfusion injury (MI/RI). Ischemia-hypoxia hypoxia/reoxygenation (H/R) models were successfully constructed by utilizing primary cardiomyocytes. KCNQ1OT1 and TIMP-3 expression in cardiomyocytes was tested. The proliferative capacity of the cells was assessed. The changes of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) contents in the supernatant of primary cardiomyocytes and Caspase-3 activity were measured. The apoptosis of primary cardiomyocytes was tested. The interactions of KCNQ1OT1, EZH2 and TIMP-3 were verified. Compared to the control group, KCNQ1OT1 expression levels, supernatant LDH and MDA levels, Caspase-3 activity, and cardiomyocyte apoptosis rate in the H/R group were elevated, and cell viability, TIMP-3 expression, and supernatant SOD levels were decreased. After KCNQ1OT1 interference or TIMP-3 overexpression, LDH and MDA levels, Caspase-3 activity, and cardiomyocyte apoptosis rate were reduced, while cell viability, TIMP-3 expression, and SOD levels were raised. Interfering TIMP-3 reversed the ameliorative effects of KCNQ1OT1 downregulation on MI/RI. Mechanistically, KCNQ1OT1 inhibited TIMP-3 expression by recruiting EZH2 to the TIMP-3 promoter region. Interference with KCNQ1OT1 could block EZH2 to the TIMP-3 promoter region and thereby up-regulate TIMP-3 expression, which possesses an ameliorative impact on MI/RI.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"101-110"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel molecular subtypes in ovarian cancer <i>via</i> zinc homeostasis-related genes and their prognostic and immune landscape implications.","authors":"Mengyu Lyu, Miao Qiu","doi":"10.4196/kjpp.25.266","DOIUrl":"10.4196/kjpp.25.266","url":null,"abstract":"<p><p>Ovarian cancer (OV) remains a leading cause of gynecologic cancer mortality, this is primarily attributed to the absence of early symptoms and reliable diagnostic biomarkers. Recent studies suggest that zinc dysregulation reshapes the tumor microenvironment, impairs immune surveillance, and promotes tumor progression. However, the prognostic implications of zinc homeostasis-related genes in OV remain poorly understood. Patients with OV were stratified into molecular subtypes based on the expression profiles of prognostic zinc homeostasis-related genes. Differential gene expression analysis was conducted using the limma package. Subsequently, we constructed a zinc homeostasis-based risk score model employing univariate Cox regression, least absolute shrinkage and selection operator regression, and multivariate Cox regression analyses. The prognostic model was validated using external datasets. Additionally, immune cell infiltration and drug sensitivity analyses were conducted to evaluate the clinical relevance of the model. Two molecular subtypes of OV were identified, each associated with distinct biological pathways. A prognostic model comprising four zinc homeostasis-related genes was developed, demonstrating robust predictive capability for overall survival and significant correlation with immune cell infiltration patterns. Drug sensitivity analysis revealed potential therapeutic targets and candidate drugs, offering insights for OV treatment strategies. This study identifies novel OV subtypes driven by zinc homeostasisrelated genes, providing insights into the genetic heterogeneity, immune landscape, and therapeutic strategies of OV. The developed prognostic model and identified candidate therapeutic agents offer valuable references for personalized treatment approaches in OV.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"139-153"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sildenafil suppresses the activation of hypertrophic scar fibroblasts by promoting the KLF15-mediated inhibition of <i>LOXL1</i> transcription.","authors":"Caihua Li, Yi Xu, Bin Cao, Ye Fan, Jie Bin, Xiuping Wang, Churuo Zeng","doi":"10.4196/kjpp.25.179","DOIUrl":"10.4196/kjpp.25.179","url":null,"abstract":"<p><p>Hypertrophic scarring (HS) is a dermal fibroproliferative disorder accompanied by pain. Sildenafil (SIL) has been shown to have a protective effect against fibrosis. This study aimed to determine the effects and mechanisms of SIL on the proliferation, migration, and extracellular matrix (ECM) production of HS fibroblasts. The expression levels of Krüppel-like factor 15 (KLF15) and lysyl oxidase-like 1 (<i>LOXL1</i>) in human dermal fibroblasts (HDFbs) and HS-derived fibroblasts (HSFbs) were determined using reverse transcription-quantitative polymerase chain reaction and Western blotting. The effect of SIL on cell proliferation, migration, ECM production, and SMAD expression was assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, transwell, and Western blotting assays, respectively. The effect of KLF15 on <i>LOXL1</i> transcriptional activity was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. Compared with HDFbs, HSFbs showed greater migration and ECM deposition. SIL inhibited cell proliferation, migration, ECM deposition, and SMAD activation in HSFbs, whereas these effects were inhibited by <i>KLF15</i> knockdown. KLF15 inhibited <i>LOXL1</i> transcription in HSFbs. <i>LOXL1</i> silencing abrogated the effect of <i>KLF15</i> knockdown on SIL-inhibited proliferation, migration, and ECM deposition. SIL inhibited the transcriptional activity of <i>LOXL1</i> by upregulating KLF15, eventually inactivating SMAD signaling and suppressing the proliferation, migration, and ECM deposition of HSFbs.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"111-124"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androsin alleviates colorectal cancer by inhibiting the PI3K/Akt-centered signaling pathway.","authors":"Yalun Zhang, Huaihao Luo, Panpan Ma, Yufang Leng, Yao Tan, Sihui Zhuo, Chaoyang Tan, Dehong Xu","doi":"10.4196/kjpp.25.275","DOIUrl":"10.4196/kjpp.25.275","url":null,"abstract":"<p><p>Androsin is a phenolic acid compound extracted from <i>Picrorhiza kurroa</i> with apocynin as its aglycone. Early studies have shown that apocynin exhibits specific inhibition towards NADPH oxidases (NOXs) and has some therapeutic effects on colorectal cancer (CRC). However, the effects and mechanisms of androsin on CRC remain unexplored. Based on the network pharmacology analysis, this study investigates the mechanisms of androsin on CRC at molecular, cellular, and animal tissue levels. Results indicate that in the high-concentration range, androsin induces apoptosis and inhibits the proliferation of CRC cell in a concentration-dependent manner, with IC₅₀ values of 56 μM and 41 μM after 48 h and 72 h, respectively. Although androsin do not affect cell viability in the low-concentration range, they significantly inhibit cell invasion, migration, and reactive oxygen species (ROS) production. In animal models, androsin suppresses tumor growth in nude mice and disrupts tumor tissues, as shown by hematoxylin-eosin staining, immunohistochemical analysis of Ki-67, and TUNEL assays. Mechanistically, androsin promotes apoptosis <i>via</i> the PI3K/Akt/mTOR/caspase3/PARP pathway in the high-concentration range, and inhibits invasion and migration <i>via</i> the NOX2/ROS/FAK/PI3K/Akt/NF-κB/MMP7 pathway in the low-concentration range. These findings not only verified the prediction from network pharmacology, but also provided a preliminary basis for exploring androsin's anti-CRC mechanisms and its potential as a therapeutic molecule or lead compound.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"155-168"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145671043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between body fat percentage and metabolic and hematologic biomarkers in Korean adults.","authors":"Ki Young Huh, Gaeun Kang","doi":"10.4196/kjpp.25.273","DOIUrl":"10.4196/kjpp.25.273","url":null,"abstract":"<p><p>Recent interest in metabolically healthy obesity highlights the need to evaluate the relationship between adiposity and hematologic and metabolic biomarkers. With the increasing use of bioelectrical impedance analysis (BIA), measuring body composition, including percent body fat (PBF), has become more accessible. This study aimed to investigate the associations between PBF and hematologic and metabolic biomarkers related to cardiometabolic health. We conducted a retrospective, cross-sectional analysis using data from the 2023 Korea National Health and Nutrition Examination Survey (KNHANES-IX), which included BIA-based body composition metrics. A total of 5,518 adults with complete records and no predefined outliers were analyzed. Survey-weighted Pearson correlation coefficients were calculated by sex and age groups, followed by multiple linear regression adjusting for sex, age, and body weight. PBF was significantly associated with alanine transaminase (β = 1.06 per % PBF), hemoglobin (β = 0.02), hematocrit (β = 0.06), total cholesterol (β = 0.48), high-density lipoprotein cholesterol (β = -0.50), low-density lipoprotein cholesterol (β = 0.62), and triglyceride (β = 2.93). No significant association was found between PBF and aspartate transaminase. Notably, the associations of PBF with alanine transaminase and triglycerides varied by sex and age group. These findings suggest that PBF may be a useful non-invasive marker for assessing cardiometabolic risk, warranting further investigation in diverse populations.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"73-83"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146068816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the causal effect and molecular signatures of serum hydroxyvitamin D on atherosclerosis: a Mendelian randomization and transcriptomic approach.","authors":"Bin Xu, Xinli Liu, Xi Liu, Jiajun Chen, Tingting Cheng, Li Chen","doi":"10.4196/kjpp.25.278","DOIUrl":"https://doi.org/10.4196/kjpp.25.278","url":null,"abstract":"<p><p>Arterial atherosclerosis is a common cardiovascular disease with serious health impact. Growing evidence suggests that serum hydroxyvitamin D may influence its progression. Investigating the causal relationship and underlying mechanisms between vitamin D and atherosclerosis is essential for developing effective prevention and treatment strategies. We conducted Mendelian randomization analysis with stringent single-nucleotide polymorphism selection to assess causal relationships. We analyzed transcriptomic datasets to identify differentially expressed genes (DEGs) and genes related to vitamin D metabolism. Feature selection was performed using Least Absolute Shrinkage and Selection Operator regression, Support Vector Machine-Recursive Feature Elimination, and random forest algorithms. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance, and a nomogram was constructed for predictive modeling. Immune cell infiltration was assessed via CIBERSORT, while Gene Set Enrichment Analysis (GSEA) was employed to explore key pathways. Quantitative real-time PCR validated gene expression. Mendelian randomization analysis confirmed that 25-hydroxyvitamin D acted a protective factor against coronary atherosclerosis. We identified 1,195 DEGs and 33 vitamin D-related genes, with four key genes demonstrating strong diagnostic accuracy in ROC curve analysis. Immune profiling revealed significant differences in nine immune cell types, and GSEA highlighted critical biological pathways involved in disease progression. The nomogram model showed high predictive performance. This multi-omics study establishes a causal relationship between serum hydroxyvitamin D levels and atherosclerosis while uncovering potential biomarkers and pathogenic mechanisms through analyses of gene expression, immune infiltration, and signaling pathways. These findings provide valuable insights into atherosclerosis research and may help guide future therapeutic strategies.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice.","authors":"Oyunbileg Bavuu, Daiju Fukuda, Uugantsetseg Munkhjargal, Byambasuren Ganbaatar, Tomoya Hara, Shusuke Yagi, Takeshi Soeki, Masataka Sata","doi":"10.4196/kjpp.25.038","DOIUrl":"10.4196/kjpp.25.038","url":null,"abstract":"<p><p>Aldosterone plays a central role in regulating blood pressure and electrolyte balance, and emerging evidence implicates its involvement in metabolic disorders. This study evaluated the metabolic effects of CS-3150, a novel nonsteroidal and selective mineralocorticoid receptor (MR) antagonist, in genetically obese db/db mice. Mice were administered CS-3150 (3 mg/kg/day) for 8 weeks while maintained on a normal chow diet. Metabolic parameters, tissue morphology, inflammatory gene expression, and insulin signaling-assessed <i>via</i> Akt phosphorylation-were examined using standard biochemical and molecular techniques. CS-3150 treatment significantly improved insulin sensitivity (p < 0.05) without notable changes in fasting blood glucose or lipid profiles. However, CS-3150 markedly reduced adipocyte size, visceral fat accumulation, and hepatic lipid deposition (p < 0.01). These changes were accompanied by decreased macrophage infiltration (p < 0.01) and reduced expression of inflammatory markers, including <i>Vcam1, Sele</i>, and <i>Il6</i> in white adipose tissue (p < 0.05). <i>In vitro</i>, aldosterone impaired insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 hepatocytes, and C2C12 myotubes. CS-3150 treatment reversed this effect, whereas the traditional MR antagonist eplerenone failed to do so at equivalent concentrations. In conclusion, CS-3150 improved insulin sensitivity in obese diabetic mice, likely through attenuation of adipose inflammation, reduction in fat accumulation, and enhancement of insulin signaling. These findings support the potential of CS-3150 as a therapeutic agent for obesity-associated metabolic dysfunction.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"31-39"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145671061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repositioning of regorafenib for renal cell carcinoma identifies <i>DDR2</i>‑associated sensitivity in ACHN models.","authors":"Jihwan Moon, Vu T A Vo, Le Tran Nhat, Minseob Eom, Yangsik Jeong","doi":"10.4196/kjpp.25.355","DOIUrl":"10.4196/kjpp.25.355","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is heterogeneous and frequently refractory to cytotoxic therapy. We investigated whether contexts with elevated DDR2-a collagenactivated receptor tyrosine kinase-are preferentially sensitive to regorafenib, a multikinase inhibitor with activity against DDR2. <i>DDR2</i> mRNA was quantified by quantitative PCR in Caki1 (clear cell), ACHN (papillary), and Caki2 (papillary) relative to HK2. Shortterm viability was assessed by a tetrazolium (MTT) assay with fourparameter logistic fits to estimate the lowest observed effect concentration (LOEC) and halfmaximal inhibitory concentration (IC₅₀). In an ACHN xenograft model, mice were randomized to vehicle or regorafenib (10 mg/kg, intraperitoneally) every 3 days for 21 days. ACHN and Caki1 expressed higher <i>DDR2</i> than HK2, whereas Caki2 was modest; ACHN xenografts retained elevation, whereas Caki2 xenografts did not. Regorafenib reduced ACHN viability with LOEC 1 μM and IC₅₀ 6.93 μM, while Caki2 first declined at 30 μM without reaching 50% inhibition. <i>In vivo</i>, regorafenib attenuated ACHN tumor growth with a significant difference by day 14. Clinically, higher <i>DDR2</i> associated with inferior overall survival in The Cancer Genome Atlas papillary cohort (KIRP), with no consistent association in the clear cell cohort (KIRC). Across <i>in vitro, in vivo</i>, and <i>in silico</i> analyses, <i>DDR2</i>-high papillary contexts exhibit preferential regorafenib sensitivity, nominating <i>DDR2</i>-enriched papillary RCC for biomarker‑guided repurposing and motivating protein‑level and genetic validation.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"41-48"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the selective inhibitory effects of Flavoxate and its analogues on two chloride channels and neuronal action potentials.","authors":"Gaohua Zhang, Anmin Zhou, Junjiang Liu, Jiping Wang, Jixia Yang, Yan Cui, Yingtong Zhao, Yaxin Song, Yunxia Li, Honglin Li, Xuan Zhang, Yuanyuan Zhang","doi":"10.4196/kjpp.25.050","DOIUrl":"10.4196/kjpp.25.050","url":null,"abstract":"<p><p>Volume-regulated anion channels (VRACs) and TMEM16A calciumactivated chloride channels (CaCCs) are distinct but share some features and can co-immunoprecipitate. Currently, there are no specific inhibitors for these channels exist. Our prior research showed Flavoxate inhibits VRAC currents in HEK293 cells under hypotonic conditions. MFCA (3-methylflavone-8-carboxylic acid, a primary active metabolite of Flavoxate) and 3-methylflavone are two structural analogues of Flavoxate. To further elucidate the specific inhibitory effects of the three flavonoids on VRACs and TMEM16A/CaCCs, the current study used patch-clamp techniques to explore their effects on the two chloride channels. Additionally, we investigated the effects of the three flavonoids on action potential (AP) firing in small dorsal root ganglion (DRG) neurons utilizing the current-clamp technique. Our findings indicate that the inhibition rates of 30 μM Flavoxate, MFCA, and 3-methylflavone on VRAC currents approximately were 78%, 46%, and 35%, with corresponding half-maximal concentration (IC₅₀) values of 1.8 μM, 18.5 μM, and 37.2 μM, respectively. In contrast, the inhibition rates of these compounds on TMEM16A/CaCC currents approximately were 14%, 15%, and 24%, with IC₅₀ values of 32.8 μM, 28.3 μM, and 26.5 μM, respectively. These results suggest that Flavoxate is highly efficient and selective for VRAC inhibition, with the 8-substituent on its flavonoid core being crucial for this selectivity. All three flavonoids strongly inhibit AP firing, indicating that their core structure contributes to analgesic effects. In summary, Flavoxate is a selective VRAC inhibitor and a potential neuropathic pain inhibitor by suppressing AP firing in small DRG neurons.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"49-59"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145671058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}