Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production
Laibin Zhang, Yuan Liu, Huanhuan Wang, Shuangyan Guo, Jieli Lv School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of ChinaCorrespondence: Laibin Zhang; Jieli Lv, School of Pharmacy, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, People...
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Dove Medical Press
2025-02-01
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| author | Zhang L Liu Y Wang H Guo S Lv J |
| author_facet | Zhang L Liu Y Wang H Guo S Lv J |
| author_sort | Zhang L |
| collection | DOAJ |
| description | Laibin Zhang, Yuan Liu, Huanhuan Wang, Shuangyan Guo, Jieli Lv School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of ChinaCorrespondence: Laibin Zhang; Jieli Lv, School of Pharmacy, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, People’s Republic of China, Email zhanglb@xxmu.edu.cn; jielilv2009@xxmu.edu.cnPurpose: Angesinenolide B (ASB), a phthalide dimer with a peroxy bridge, is uniquely isolated from Chinese medicine Angelica sinensis radix and demonstrates significant anti-inflammatory properties. The objective of the current study was to evaluate the anti-inflammatory function of ASB and the potential mechanism in lipopolysaccharide (LPS)-stimulated macrophages and CuSO4-induced zebrafish models.Methods: The level of nitric oxide (NO), a proinflammatory mediator, in LPS-stimulated RAW264.7 cells was quantified using Griess method. ELISA was employed to investigate the generation of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), while qRT-PCR was utilized to analyze the mRNA expressions of TNF-α, IL-6, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Fluorescence microscopy and flow cytometry were employed for the determination of ROS generation. Western blot and immunofluorescence techniques were utilized to assess the impact of ASB on iNOS and COX-2, and on the NF-κB, MAPK and STATs signaling pathways. Moreover, the affinities between ASB and the target proteins were verified by molecular docking analysis. In vivo, ROS generation was explored using fluorescent probe DCFH-DA, and the TNF-α and IL-6 mRNA expressions were also evaluated in CuSO4-induced zebrafish inflammation model.Results: ASB treatment was found to suppress the levels of NO, TNF-α, IL-6 and ROS, restrain the expressions of iNOS and COX-2 proteins and mRNA, as well as down-regulate MAPK and STATs signaling pathways in LPS-stimulated RAW264.7 cells. Furthermore, the administration of ASB effectively attenuated the overproduction ROS and the high mRNA expressions of TNF-α and IL-6 in a zebrafish model of inflammation induced by CuSO4.Conclusion: ASB has the potentiality to reduce the levels of proinflammatory mediators and cytokines, decrease ROS production, and also down-regulate the MAPK and STATs signaling pathways, thereby exerting an anti-inflammatory effect. This implies that ASB could potentially serve as a viable approach for addressing inflammatory conditions. Keywords: Angesinenolide B, anti-inflammation, signaling pathway, cytokine, ROS |
| format | Article |
| id | doaj-art-feeae84ae03747e4a9c4208b556f9bfa |
| institution | Kabale University |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
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| series | Journal of Inflammation Research |
| spelling | doaj-art-feeae84ae03747e4a9c4208b556f9bfa2025-02-04T17:15:40ZengDove Medical PressJournal of Inflammation Research1178-70312025-02-01Volume 181557157499815Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS ProductionZhang LLiu YWang HGuo SLv JLaibin Zhang, Yuan Liu, Huanhuan Wang, Shuangyan Guo, Jieli Lv School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of ChinaCorrespondence: Laibin Zhang; Jieli Lv, School of Pharmacy, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, People’s Republic of China, Email zhanglb@xxmu.edu.cn; jielilv2009@xxmu.edu.cnPurpose: Angesinenolide B (ASB), a phthalide dimer with a peroxy bridge, is uniquely isolated from Chinese medicine Angelica sinensis radix and demonstrates significant anti-inflammatory properties. The objective of the current study was to evaluate the anti-inflammatory function of ASB and the potential mechanism in lipopolysaccharide (LPS)-stimulated macrophages and CuSO4-induced zebrafish models.Methods: The level of nitric oxide (NO), a proinflammatory mediator, in LPS-stimulated RAW264.7 cells was quantified using Griess method. ELISA was employed to investigate the generation of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), while qRT-PCR was utilized to analyze the mRNA expressions of TNF-α, IL-6, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Fluorescence microscopy and flow cytometry were employed for the determination of ROS generation. Western blot and immunofluorescence techniques were utilized to assess the impact of ASB on iNOS and COX-2, and on the NF-κB, MAPK and STATs signaling pathways. Moreover, the affinities between ASB and the target proteins were verified by molecular docking analysis. In vivo, ROS generation was explored using fluorescent probe DCFH-DA, and the TNF-α and IL-6 mRNA expressions were also evaluated in CuSO4-induced zebrafish inflammation model.Results: ASB treatment was found to suppress the levels of NO, TNF-α, IL-6 and ROS, restrain the expressions of iNOS and COX-2 proteins and mRNA, as well as down-regulate MAPK and STATs signaling pathways in LPS-stimulated RAW264.7 cells. Furthermore, the administration of ASB effectively attenuated the overproduction ROS and the high mRNA expressions of TNF-α and IL-6 in a zebrafish model of inflammation induced by CuSO4.Conclusion: ASB has the potentiality to reduce the levels of proinflammatory mediators and cytokines, decrease ROS production, and also down-regulate the MAPK and STATs signaling pathways, thereby exerting an anti-inflammatory effect. This implies that ASB could potentially serve as a viable approach for addressing inflammatory conditions. Keywords: Angesinenolide B, anti-inflammation, signaling pathway, cytokine, ROShttps://www.dovepress.com/angesinenolide-b-a-phthalide-dimeric-peroxide-exerts-anti-inflammatory-peer-reviewed-fulltext-article-JIRangesinenolide banti-inflammationsignaling pathwaycytokineros |
| spellingShingle | Zhang L Liu Y Wang H Guo S Lv J Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production Journal of Inflammation Research angesinenolide b anti-inflammation signaling pathway cytokine ros |
| title | Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production |
| title_full | Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production |
| title_fullStr | Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production |
| title_full_unstemmed | Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production |
| title_short | Angesinenolide B, A Phthalide Dimeric Peroxide, Exerts Anti-Inflammatory Properties by Suppressing MAPK/STATs Signaling Pathways and ROS Production |
| title_sort | angesinenolide b a phthalide dimeric peroxide exerts anti inflammatory properties by suppressing mapk stats signaling pathways and ros production |
| topic | angesinenolide b anti-inflammation signaling pathway cytokine ros |
| url | https://www.dovepress.com/angesinenolide-b-a-phthalide-dimeric-peroxide-exerts-anti-inflammatory-peer-reviewed-fulltext-article-JIR |
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