The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities
Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. <i>Carrichtera annua</i> extract proved to possess potent antioxidant...
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MDPI AG
2021-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/6/825 |
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| author | Enas E. Eltamany Sameh S. Elhady Mohamed S. Nafie Haidy A. Ahmed Dina M. Abo-Elmatty Safwat A. Ahmed Jihan M. Badr Asmaa R. Abdel-Hamed |
| author_facet | Enas E. Eltamany Sameh S. Elhady Mohamed S. Nafie Haidy A. Ahmed Dina M. Abo-Elmatty Safwat A. Ahmed Jihan M. Badr Asmaa R. Abdel-Hamed |
| author_sort | Enas E. Eltamany |
| collection | DOAJ |
| description | Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. <i>Carrichtera annua</i> extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on <i>C. annua</i> ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing <sup>1</sup>H- and <sup>13</sup>C-NMR spectral analyses. The isolated phytochemicals were <i>trans</i>-ferulic acid (<b>1</b>), kaempferol (<b>2</b>), <i>p</i>-coumaric acid (<b>3</b>), luteolin (<b>4</b>) and quercetin (<b>5</b>). Regarding our biological study, <i>C. annua</i> has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. <i>C. annua</i> has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—<i>C. annua</i> extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of <i>C. annua</i> constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that <i>C. annua</i> is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals. |
| first_indexed | 2024-03-10T11:10:07Z |
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| language | English |
| last_indexed | 2024-03-10T11:10:07Z |
| publishDate | 2021-05-01 |
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| spelling | doaj.art-359f0326426b4b44a50ed12f8bdaf9122023-11-21T20:48:23ZengMDPI AGAntioxidants2076-39212021-05-0110682510.3390/antiox10060825The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal ToxicitiesEnas E. Eltamany0Sameh S. Elhady1Mohamed S. Nafie2Haidy A. Ahmed3Dina M. Abo-Elmatty4Safwat A. Ahmed5Jihan M. Badr6Asmaa R. Abdel-Hamed7Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptCisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. <i>Carrichtera annua</i> extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on <i>C. annua</i> ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing <sup>1</sup>H- and <sup>13</sup>C-NMR spectral analyses. The isolated phytochemicals were <i>trans</i>-ferulic acid (<b>1</b>), kaempferol (<b>2</b>), <i>p</i>-coumaric acid (<b>3</b>), luteolin (<b>4</b>) and quercetin (<b>5</b>). Regarding our biological study, <i>C. annua</i> has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. <i>C. annua</i> has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—<i>C. annua</i> extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of <i>C. annua</i> constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that <i>C. annua</i> is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.https://www.mdpi.com/2076-3921/10/6/825<i>Carrichtera annua</i>cisplatinhepatotoxicitynephrotoxicityphenolic acidsflavonoids |
| spellingShingle | Enas E. Eltamany Sameh S. Elhady Mohamed S. Nafie Haidy A. Ahmed Dina M. Abo-Elmatty Safwat A. Ahmed Jihan M. Badr Asmaa R. Abdel-Hamed The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities Antioxidants <i>Carrichtera annua</i> cisplatin hepatotoxicity nephrotoxicity phenolic acids flavonoids |
| title | The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities |
| title_full | The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities |
| title_fullStr | The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities |
| title_full_unstemmed | The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities |
| title_short | The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities |
| title_sort | antioxidant i carrichtera annua i dc ethanolic extract counteracts cisplatin triggered hepatic and renal toxicities |
| topic | <i>Carrichtera annua</i> cisplatin hepatotoxicity nephrotoxicity phenolic acids flavonoids |
| url | https://www.mdpi.com/2076-3921/10/6/825 |
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