{"title":"穿心术内酯通过抑制JNK和NF-κB通路减少镉暴露的胶质母细胞瘤细胞因子释放和环氧合酶-2的表达","authors":"Thitima Kasemsuk, Pornpun Vivithanaporn, Pichsinee Woonfak, Phisit Khemawoot","doi":"10.2147/JEP.S506062","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is associated with brain cancer and several neurodegenerative diseases. At nontoxic concentrations, the environmental pollutant cadmium is known to increase the secretion of pro-inflammatory cytokines, including interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by activating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways. Andrographolide, a diterpenoid lactone, exhibits anti-inflammatory and antioxidant activity in vitro and in vivo. Hence, in this study, we aimed to determine the effects of andrographolide on cadmium-induced inflammation and the underlying mechanisms in U-87 MG glioblastoma cells.</p><p><strong>Methods: </strong>U-87 MG cells, obtained from American Type Culture Collection (ATCC), are adherent cells derived from malignant gliomas and express the astrocyte cell marker glial fibrillary acidic protein. Cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay. Human IL-6, IL-8, and CCL2 levels were measured using enzyme-linked immunosorbent assays (ELISAs). Cyclooxygenase-2 (COX-2) and the proteins involved in the MAPK and NF-κB pathways were detected via Western blotting.</p><p><strong>Results: </strong>Treating cells with andrographolide or cadmium alone or in combination did not alter cell viability. Andrographolide decreased cadmium-induced IL-6, IL-8, and CCL2 release and downregulated cadmium-induced COX-2 expression. Andrographolide also reduced the levels of cadmium-induced phospho-Jun N-terminal kinase (JNK) and phospho-p65.</p><p><strong>Conclusion: </strong>In this study, andrographolide exerted an anti-inflammatory effect on cadmium-induced inflammation by inhibiting the JNK and NF-κB pathways. These findings have implications for the development of therapies for cadmium poisoning since the efficacy of current therapeutic approaches is limited.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"169-179"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970311/pdf/","citationCount":"0","resultStr":"{\"title\":\"Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium.\",\"authors\":\"Thitima Kasemsuk, Pornpun Vivithanaporn, Pichsinee Woonfak, Phisit Khemawoot\",\"doi\":\"10.2147/JEP.S506062\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Neuroinflammation is associated with brain cancer and several neurodegenerative diseases. At nontoxic concentrations, the environmental pollutant cadmium is known to increase the secretion of pro-inflammatory cytokines, including interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by activating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways. Andrographolide, a diterpenoid lactone, exhibits anti-inflammatory and antioxidant activity in vitro and in vivo. Hence, in this study, we aimed to determine the effects of andrographolide on cadmium-induced inflammation and the underlying mechanisms in U-87 MG glioblastoma cells.</p><p><strong>Methods: </strong>U-87 MG cells, obtained from American Type Culture Collection (ATCC), are adherent cells derived from malignant gliomas and express the astrocyte cell marker glial fibrillary acidic protein. Cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay. Human IL-6, IL-8, and CCL2 levels were measured using enzyme-linked immunosorbent assays (ELISAs). Cyclooxygenase-2 (COX-2) and the proteins involved in the MAPK and NF-κB pathways were detected via Western blotting.</p><p><strong>Results: </strong>Treating cells with andrographolide or cadmium alone or in combination did not alter cell viability. Andrographolide decreased cadmium-induced IL-6, IL-8, and CCL2 release and downregulated cadmium-induced COX-2 expression. Andrographolide also reduced the levels of cadmium-induced phospho-Jun N-terminal kinase (JNK) and phospho-p65.</p><p><strong>Conclusion: </strong>In this study, andrographolide exerted an anti-inflammatory effect on cadmium-induced inflammation by inhibiting the JNK and NF-κB pathways. These findings have implications for the development of therapies for cadmium poisoning since the efficacy of current therapeutic approaches is limited.</p>\",\"PeriodicalId\":15846,\"journal\":{\"name\":\"Journal of Experimental Pharmacology\",\"volume\":\"17 \",\"pages\":\"169-179\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-03-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970311/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Experimental Pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/JEP.S506062\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/JEP.S506062","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium.
Background: Neuroinflammation is associated with brain cancer and several neurodegenerative diseases. At nontoxic concentrations, the environmental pollutant cadmium is known to increase the secretion of pro-inflammatory cytokines, including interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by activating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways. Andrographolide, a diterpenoid lactone, exhibits anti-inflammatory and antioxidant activity in vitro and in vivo. Hence, in this study, we aimed to determine the effects of andrographolide on cadmium-induced inflammation and the underlying mechanisms in U-87 MG glioblastoma cells.
Methods: U-87 MG cells, obtained from American Type Culture Collection (ATCC), are adherent cells derived from malignant gliomas and express the astrocyte cell marker glial fibrillary acidic protein. Cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay. Human IL-6, IL-8, and CCL2 levels were measured using enzyme-linked immunosorbent assays (ELISAs). Cyclooxygenase-2 (COX-2) and the proteins involved in the MAPK and NF-κB pathways were detected via Western blotting.
Results: Treating cells with andrographolide or cadmium alone or in combination did not alter cell viability. Andrographolide decreased cadmium-induced IL-6, IL-8, and CCL2 release and downregulated cadmium-induced COX-2 expression. Andrographolide also reduced the levels of cadmium-induced phospho-Jun N-terminal kinase (JNK) and phospho-p65.
Conclusion: In this study, andrographolide exerted an anti-inflammatory effect on cadmium-induced inflammation by inhibiting the JNK and NF-κB pathways. These findings have implications for the development of therapies for cadmium poisoning since the efficacy of current therapeutic approaches is limited.