Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium
Thitima Kasemsuk,1 Pornpun Vivithanaporn,2 Pichsinee Woonfak,2 Phisit Khemawoot2 1Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand; 2Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospi...
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Dove Medical Press
2025-03-01
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| author | Kasemsuk T Vivithanaporn P Woonfak P Khemawoot P |
| author_facet | Kasemsuk T Vivithanaporn P Woonfak P Khemawoot P |
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| description | Thitima Kasemsuk,1 Pornpun Vivithanaporn,2 Pichsinee Woonfak,2 Phisit Khemawoot2 1Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand; 2Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, 10540, ThailandCorrespondence: Pornpun Vivithanaporn; Phisit Khemawoot, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, 10540, Thailand, Email pornpun.viv@mahidol.ac.th; phisit.khe@mahidol.ac.thBackground: 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. Keywords: andrographolide, cadmium, inflammation, MAPK, NF-κB |
| format | Article |
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| spelling | doaj-art-b4f0892da13b415d89cf514ec08b0f022025-08-20T01:54:57ZengDove Medical PressJournal of Experimental Pharmacology1179-14542025-03-01Volume 17169179101642Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to CadmiumKasemsuk TVivithanaporn PWoonfak PKhemawoot PThitima Kasemsuk,1 Pornpun Vivithanaporn,2 Pichsinee Woonfak,2 Phisit Khemawoot2 1Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand; 2Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, 10540, ThailandCorrespondence: Pornpun Vivithanaporn; Phisit Khemawoot, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, 10540, Thailand, Email pornpun.viv@mahidol.ac.th; phisit.khe@mahidol.ac.thBackground: 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. Keywords: andrographolide, cadmium, inflammation, MAPK, NF-κBhttps://www.dovepress.com/andrographolide-reduces-cytokine-release-and-cyclooxygenase-2-expressi-peer-reviewed-fulltext-article-JEPandrographolidecadmiuminflammationmapknf-κb |
| spellingShingle | Kasemsuk T Vivithanaporn P Woonfak P Khemawoot P Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium Journal of Experimental Pharmacology andrographolide cadmium inflammation mapk nf-κb |
| title | Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium |
| title_full | Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium |
| title_fullStr | Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium |
| title_full_unstemmed | Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium |
| title_short | Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium |
| title_sort | andrographolide reduces cytokine release and cyclooxygenase 2 expression by inhibiting the jnk and nf kappa b pathways in glioblastoma cells exposed to cadmium |
| topic | andrographolide cadmium inflammation mapk nf-κb |
| url | https://www.dovepress.com/andrographolide-reduces-cytokine-release-and-cyclooxygenase-2-expressi-peer-reviewed-fulltext-article-JEP |
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