Korean Journal of Physiology & Pharmacology最新文献

{"title":"Colla Carapacis et Plastri ameliorates postmenopausal osteoporosis and macrophage immunity by modulating the RANK/RANKL/OPG signaling pathway in ovariectomized rats.","authors":"Wenyuan Wan, Zhenling Peng, Juan Luo, Jie Luo, Yingying Zhu","doi":"10.4196/kjpp.24.248","DOIUrl":"10.4196/kjpp.24.248","url":null,"abstract":"<p><p>Postmenopausal osteoporosis (PMOP) is characterized by estrogen depletion, leading to skeletal demineralization and fractures. This study examines the impact of Colla Carapacis et Plastri (CCP) on PMOP in ovariectomized rats. Within this research, we replicated a rat model of PMOP through ovariectomy. The model rats were then intervened with low-dose CCP, high-dose CCP, and estrogen (positive control). The body weight was recorded, and the uterine index (UMI) was calculated. After intervention with CCP and the receptor activator of nuclear factor Κb (RANK) ligand (RANKL) inhibitor denosumab in PMOP rats, the bone microstructure, bone metabolism, macrophage M1/M2, and RANK/RANKL/Osteoprotegerin (OPG) signaling pathway-related factors were examined. These were conducted through hematoxylin and eosin staining, Biochemical kits and immunohistochemistry, respectively. The ovariectomized rat model was successfully established. Compared to the Sham group, rats in the Model group exhibited increased body weight, reduced UMI, and extensive damage to the microstructure of the femur. After intervention with CCP, the bone tissue microstructure of PMOP rats was repaired, as observed in increased levels of blood calcium level. Furthermore, CCP intervention led to reduced M1 macrophage levels (iNOS and CD86) and increased M2 macrophage levels (CD163 and CD206). Additionally, CCP treatment decreased RANK and RANKL expression levels and increased expression of OPG. The addition of denosumab further enhanced the effects of CCP. CCP can improve PMOP and regulate macrophage immunity in ovariectomized rats by modulating the RANK/RANKL/OPG signaling pathway.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"443-454"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042962","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":"Emerging role of circular RNAs in diabetic retinopathy.","authors":"Hyunjong Kim, Juhee Ryu","doi":"10.4196/kjpp.24.389","DOIUrl":"10.4196/kjpp.24.389","url":null,"abstract":"<p><p>Diabetic retinopathy (DR), a significant complication that affects the retina of individuals with diabetes, poses a severe threat to their visual health. DR is classified into stages ranging from non-proliferative to proliferative forms. As the disease progresses, pathological neovascularization and hemorrhage in the retina or vitreous can occur, potentially leading to vision impairment or blindness. Current treatments for DR include intravitreal injections of anti-vascular endothelial growth factor drugs and surgical interventions such as laser photocoagulation. However, these treatments are associated with various complications and side effects. Therefore, cellular and epigenetic studies are necessary to better understand the pathogenesis of DR, which may lead to the development of novel therapeutic strategies. Several studies have demonstrated the role of circular RNAs (circRNAs) in the pathogenesis and progression of DR. CircRNAs have been shown to regulate the expression of genes involved in the proliferation, differentiation, or angiogenesis of different retinal cells, thereby influencing their function. Therefore, this review aims to investigate the role of circRNAs in different retinal cell types in DR and evaluate their potential as diagnostic and therapeutic targets for the disease.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"385-397"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082083","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":"Quetiapine competitively inhibits 5-HT₃ receptor-mediated currents in NCB20 neuroblastoma cells.","authors":"Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung","doi":"10.4196/kjpp.24.363","DOIUrl":"10.4196/kjpp.24.363","url":null,"abstract":"<p><p>The 5-hydroxytryptamine type₃ (5-HT₃) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT₃ receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (E_max), suggesting a competitive inhibition. Quetiapine's IC₅₀ varied with 5-HT concentration and treatment condition. The IC₅₀ value of quetiapine was 0.58 μM with 3 μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC₅₀ from 25.23 μM to 0.20 μM. Interaction kinetics experiments revealed an IC₅₀ of 5.17 μM for an open state of the 5-HT₃ receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT₃ receptor by quetiapine was voltage-independent, and quetiapine exhibited no use-dependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT₃ receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"373-384"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848235","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":"Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells.","authors":"Hao Jin, Yu Ran Lee, Sungmin Kim, Eun-Ok Lee, Hee Kyoung Joo, Heon Jong Yoo, Cuk-Seong Kim, Byeong Hwa Jeon","doi":"10.4196/kjpp.24.273","DOIUrl":"10.4196/kjpp.24.273","url":null,"abstract":"<p><p>The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3. The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"293-305"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574687","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":"Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.","authors":"Jiaqi Ding, Shenjie Zhang, Qi Li, Boyu Xia, Jingjing Wu, Xu Lu, Chao Huang, Xiaomei Yuan, Qingsheng You","doi":"10.4196/kjpp.24.200","DOIUrl":"10.4196/kjpp.24.200","url":null,"abstract":"<p><p>Geraniin, a polyphenol derived from the fruit peel of <i>Nephelium lappaceum</i> L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue. Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in B-cell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells. These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"307-319"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689684","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":"Enhancing doxorubicin's anticancer impact in colorectal cancer by targeting the Akt/Gsk3β/mTOR-SREBP1 signaling axis with an HDAC inhibitor.","authors":"Huaxin Zhao, Yanling Wu, Soo Mi Kim","doi":"10.4196/kjpp.24.274","DOIUrl":"https://doi.org/10.4196/kjpp.24.274","url":null,"abstract":"<p><p>Colorectal cancer ranks third in global incidence and is the second leading cause of cancer-related mortality. Doxorubicin, an anthracycline chemotherapeutic drug, is integral to current cancer treatment protocols. However, toxicity and resistance to doxorubicin poses a significant challenge to effective therapy. Panobinostat has emerged as a critical agent in colorectal cancer treatment due to its potential to overcome doxorubicin resistance and enhance the efficacy of existing therapeutic protocols. This study aimed to evaluate the capability of panobinostat to surmount doxorubicin toxicity and resistance in colorectal cancer. Specifically, we assessed the efficacy of panobinostat in enhancing the therapeutic response to doxorubicin in colorectal cancer cells and explored the potential synergistic effects of their combined treatment. Our results demonstrate that the combination treatment significantly reduces cell viability and colony-forming ability in colorectal cancer cells compared to individual treatments. The combination induces significant apoptosis, as evidenced by increased levels of cleaved PARP and cleaved caspase-9, while also resulting in a greater reduction in p-Akt/p-GSK-3β/mTOR expression, along with substantial decreases in c-Myc and SREBP-1 levels, compared to monotherapies. Consistent with the <i>in vitro</i> experimental results, the combination treatment significantly inhibited tumor formation in colorectal cancer xenograft nude mice compared to the groups treated with either agent alone. In conclusion, our research suggests that the panobinostat effectively enhances the effect of doxorubicin and combination of two drugs significantly reduced colorectal cancer tumor growth by targeting the Akt/GSK-3β/mTOR signaling pathway, indicating a synergistic therapeutic potential of these two drugs in colorectal cancer treatment.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"29 3","pages":"321-335"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050860","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":"Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma.","authors":"Wenwen Yu, Yubo Shi, Xiaoqiong Bao, Xiangxiang Chen, Yangyang Ni, Jincong Wang, Hua Ye","doi":"10.4196/kjpp.24.275","DOIUrl":"10.4196/kjpp.24.275","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan- mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"337-347"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574618","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":"Haloperidol, a typical antipsychotic, inhibits 5-HT₃ receptor-mediated currents in NCB-20 cells: a whole-cell patch-clamp study","authors":"Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung","doi":"10.4196/kjpp.24.320","DOIUrl":"10.4196/kjpp.24.320","url":null,"abstract":"<p><p>Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT)₃ receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT₃ receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E_max) and an increase in EC₅₀ observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT₃ receptors. Haloperidol inhibited the activation of 5-HT₃ receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT₃ receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT₃ receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT₃ receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT₃ receptors and pharmacological actions of antipsychotics.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"349-358"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689686","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 telomere-related diagnostic markers in osteoarthritis based on bioinformatics analysis and machine learning.","authors":"Sheng Xu, Jia Ye, Xiaochong Cai","doi":"10.4196/kjpp.24.322","DOIUrl":"https://doi.org/10.4196/kjpp.24.322","url":null,"abstract":"<p><p>Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues. Finally, potential drugs targeting candidate genes were predicted. Three telomere-related genes, <i>PGD</i>, <i>SLC7A5</i>, and <i>TKT</i>, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with <i>PGD</i>, <i>SLC7A5</i>, and <i>TKT</i> was reduced. Recognizing telomere-related genes <i>PGD</i>, <i>SLC7A5</i>, and <i>TKT</i> as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"29 3","pages":"359-372"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026823","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":"Shikonin attenuates blood-brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/Nrf2/HO-1 signaling.","authors":"Guanghu Li, Yang'e Yi, Sheng Qian, Xianping Xu, Hao Min, Jianpeng Wang, Pan Guo, Tingting Yu, Zhiqiang Zhang","doi":"10.4196/kjpp.24.182","DOIUrl":"https://doi.org/10.4196/kjpp.24.182","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of <i>Lithospermum erythrorhizon</i>, on oxidative stress and blood-brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"29 3","pages":"283-291"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058064","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}