Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation
Background: Cisplatin (CP) is a chemotherapeutic agent notorious for its cardiotoxic effects. Scopoletin, a natural coumarin, has shown potential due to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which may counteract CP-induced cardiotoxicity. Purpose: The study aimed to expl...
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Elsevier
2025-02-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031325000119 |
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| author | Esam Qnais Omar Gammoh Yousra Bsieso Mohammad Alqudah Mohammad Wedyan Sara Altaber Alaa A.A. Aljabali Abdelrahim Alqudah Taher Hatahet |
| author_facet | Esam Qnais Omar Gammoh Yousra Bsieso Mohammad Alqudah Mohammad Wedyan Sara Altaber Alaa A.A. Aljabali Abdelrahim Alqudah Taher Hatahet |
| author_sort | Esam Qnais |
| collection | DOAJ |
| description | Background: Cisplatin (CP) is a chemotherapeutic agent notorious for its cardiotoxic effects. Scopoletin, a natural coumarin, has shown potential due to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which may counteract CP-induced cardiotoxicity. Purpose: The study aimed to explore the cardioprotective effects of scopoletin against CP-induced damage in mice, focusing on histopathological changes, cardiac biomarkers, oxidative stress, inflammation, apoptosis, and the modulation of key signaling pathways. Study Design: A controlled experimental design was employed to evaluate scopoletin's efficacy in alleviating CP-induced cardiotoxicity, with dosing variations to assess dose dependency. Methods: Male mice were allocated into five groups: a control group, a cisplatin-only group, two groups treated with low (50 mg/kg/day) and high doses (150 mg/kg/day) of scopoletin in conjunction with cisplatin, and a scopoletin-only group. The interventions were administered over a period of one week, with cardiac damage assessed through histopathological examinations, serum cardiac biomarker measurements, and analyses of oxidative stress, inflammatory cytokines, and apoptosis-related proteins. The efficacy of scopoletin in modulating the p62/Keap1/Nrf2 pathway was also examined. Results: Histopathological assessments showed less tissue damage in scopoletin-treated groups (p < 0.01). Cardiac biomarkers were significantly lower in l- and H-scopoletin groups compared to the CP-only group (p < 0.05, p < 0.01). Scopoletin effectively reduced ROS and MDA levels while enhancing antioxidant enzymes like SOD, CAT, and GSH (p < 0.01). With scopoletin treatment, inflammatory cytokines TNF-α and IL-6 were notably reduced (p < 0.01). Apoptosis analysis revealed lower levels of pro-apoptotic proteins and higher levels of Bcl-2 in scopoletin groups (p < 0.05, p < 0.01). Significantly, scopoletin restored the function of the p62/Keap1/Nrf2 signaling pathway (p < 0.01). Conclusion: The findings suggest scopoletin's potential as an adjunctive therapy in cancer treatment to mitigate CP's adverse effects, warranting further clinical investigation. |
| format | Article |
| id | doaj-art-b1308d743a80470d8b75104376038bd9 |
| institution | Kabale University |
| issn | 2667-0313 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj-art-b1308d743a80470d8b75104376038bd92025-02-10T04:35:21ZengElsevierPhytomedicine Plus2667-03132025-02-0151100738Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammationEsam Qnais0Omar Gammoh1Yousra Bsieso2Mohammad Alqudah3Mohammad Wedyan4Sara Altaber5Alaa A.A. Aljabali6Abdelrahim Alqudah7Taher Hatahet8Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, JordanDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid 21163, JordanDepartment of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, JordanPhysiology Department, School of Medicine and Biomedical Sciences, Arabian Gulf University, Manama, BahrainDepartment of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, JordanDepartment of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, JordanDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid, 21163, JordanDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan; Corresponding author at: Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, the Hashemite University, 13133, Damascus highway, Zarqa, Jordan.School of Pharmacy, Queens University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UKBackground: Cisplatin (CP) is a chemotherapeutic agent notorious for its cardiotoxic effects. Scopoletin, a natural coumarin, has shown potential due to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which may counteract CP-induced cardiotoxicity. Purpose: The study aimed to explore the cardioprotective effects of scopoletin against CP-induced damage in mice, focusing on histopathological changes, cardiac biomarkers, oxidative stress, inflammation, apoptosis, and the modulation of key signaling pathways. Study Design: A controlled experimental design was employed to evaluate scopoletin's efficacy in alleviating CP-induced cardiotoxicity, with dosing variations to assess dose dependency. Methods: Male mice were allocated into five groups: a control group, a cisplatin-only group, two groups treated with low (50 mg/kg/day) and high doses (150 mg/kg/day) of scopoletin in conjunction with cisplatin, and a scopoletin-only group. The interventions were administered over a period of one week, with cardiac damage assessed through histopathological examinations, serum cardiac biomarker measurements, and analyses of oxidative stress, inflammatory cytokines, and apoptosis-related proteins. The efficacy of scopoletin in modulating the p62/Keap1/Nrf2 pathway was also examined. Results: Histopathological assessments showed less tissue damage in scopoletin-treated groups (p < 0.01). Cardiac biomarkers were significantly lower in l- and H-scopoletin groups compared to the CP-only group (p < 0.05, p < 0.01). Scopoletin effectively reduced ROS and MDA levels while enhancing antioxidant enzymes like SOD, CAT, and GSH (p < 0.01). With scopoletin treatment, inflammatory cytokines TNF-α and IL-6 were notably reduced (p < 0.01). Apoptosis analysis revealed lower levels of pro-apoptotic proteins and higher levels of Bcl-2 in scopoletin groups (p < 0.05, p < 0.01). Significantly, scopoletin restored the function of the p62/Keap1/Nrf2 signaling pathway (p < 0.01). Conclusion: The findings suggest scopoletin's potential as an adjunctive therapy in cancer treatment to mitigate CP's adverse effects, warranting further clinical investigation.http://www.sciencedirect.com/science/article/pii/S2667031325000119ScopoletinCisplatinCardiotoxicityNrf2Oxidative stressInflammation |
| spellingShingle | Esam Qnais Omar Gammoh Yousra Bsieso Mohammad Alqudah Mohammad Wedyan Sara Altaber Alaa A.A. Aljabali Abdelrahim Alqudah Taher Hatahet Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation Phytomedicine Plus Scopoletin Cisplatin Cardiotoxicity Nrf2 Oxidative stress Inflammation |
| title | Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation |
| title_full | Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation |
| title_fullStr | Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation |
| title_full_unstemmed | Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation |
| title_short | Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation |
| title_sort | scopoletin as a cardioprotective agent against cisplatin induced oxidative stress and inflammation |
| topic | Scopoletin Cisplatin Cardiotoxicity Nrf2 Oxidative stress Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2667031325000119 |
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