<i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling
Despite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether <i>Marrubium alysson</i> L. (<i>M. alysson</i> L.) methanolic extract an...
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MDPI AG
2022-09-01
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| Series: | Plants |
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| Online Access: | https://www.mdpi.com/2223-7747/11/17/2309 |
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| author | Reda F. A. Abdelhameed Asmaa I. Ali Sameh S. Elhady Hend E. Abo Mansour Eman T. Mehanna Sarah M. Mosaad Salma A. Ibrahim Rawan H. Hareeri Jihan M. Badr Nermeen A. Eltahawy |
| author_facet | Reda F. A. Abdelhameed Asmaa I. Ali Sameh S. Elhady Hend E. Abo Mansour Eman T. Mehanna Sarah M. Mosaad Salma A. Ibrahim Rawan H. Hareeri Jihan M. Badr Nermeen A. Eltahawy |
| author_sort | Reda F. A. Abdelhameed |
| collection | DOAJ |
| description | Despite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether <i>Marrubium alysson</i> L. (<i>M. alysson</i> L.) methanolic extract and its polyphenol fraction could protect mouse testicles from MTX-induced damage. We also investigated the protective effects of three selected pure flavonoid components of <i>M. alysson</i> L. extract. Mice were divided into seven groups (n = 8): (1) normal control, (2) MTX, (3) Methanolic extract + MTX, (4) Polyphenolic fraction + MTX, (5) Kaempferol + MTX, (6) Quercetin + MTX, and (7) Rutin + MTX. Pre-treatment of mice with the methanolic extract, the polyphenolic fraction of <i>M. alysson</i> L. and the selected pure compounds ameliorated the testicular histopathological damage and induced a significant increase in the serum testosterone level and testicular antioxidant enzymes along with a remarkable decline in the malondialdehyde (MDA) level <i>versus</i> MTX alone. Significant down-regulation of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), p53 and miRNA-29a testicular expression was also observed in all the protected groups. Notably, the polyphenolic fraction of <i>M. alysson</i> L. displayed a more pronounced decline in the testicular levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and MDA, with higher testosterone levels relative to the methanolic extract. Further improvements in the Johnsen score, histopathological results and all biochemical assays were achieved by pre-treatment with the three selected pure compounds kaempferol, quercetin and rutin. In conclusion, <i>M. alysson</i> L. could protect against MTX-induced testicular injury by its antioxidant, anti-inflammatory, antiapoptotic activities and through the regulation of the miRNA-29a testicular expression. The present study also included chemical profiling of <i>M. alysson</i> L. extract, which was accomplished by LC-ESI-TOF-MS/MS analysis. Forty compounds were provisionally assigned, comprising twenty compounds discovered in the positive mode and seventeen detected in the negative mode. |
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| spelling | doaj.art-8fac93de93824af7bbd927cdac23d5cb2023-11-23T13:56:31ZengMDPI AGPlants2223-77472022-09-011117230910.3390/plants11172309<i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic ProfilingReda F. A. Abdelhameed0Asmaa I. Ali1Sameh S. Elhady2Hend E. Abo Mansour3Eman T. Mehanna4Sarah M. Mosaad5Salma A. Ibrahim6Rawan H. Hareeri7Jihan M. Badr8Nermeen A. Eltahawy9Department of Pharmacognosy, Faculty of Pharmacy, Galala University, New Galala 43713, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Misr International University, Cairo 12585, EgyptDepartment of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin El-Koum 32511, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDivision of Pharmacology and Therapeutics, Department of Continuous Medical Education, General Authority of Healthcare, Ismailia 41522, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Misr International University, Cairo 12585, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDespite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether <i>Marrubium alysson</i> L. (<i>M. alysson</i> L.) methanolic extract and its polyphenol fraction could protect mouse testicles from MTX-induced damage. We also investigated the protective effects of three selected pure flavonoid components of <i>M. alysson</i> L. extract. Mice were divided into seven groups (n = 8): (1) normal control, (2) MTX, (3) Methanolic extract + MTX, (4) Polyphenolic fraction + MTX, (5) Kaempferol + MTX, (6) Quercetin + MTX, and (7) Rutin + MTX. Pre-treatment of mice with the methanolic extract, the polyphenolic fraction of <i>M. alysson</i> L. and the selected pure compounds ameliorated the testicular histopathological damage and induced a significant increase in the serum testosterone level and testicular antioxidant enzymes along with a remarkable decline in the malondialdehyde (MDA) level <i>versus</i> MTX alone. Significant down-regulation of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), p53 and miRNA-29a testicular expression was also observed in all the protected groups. Notably, the polyphenolic fraction of <i>M. alysson</i> L. displayed a more pronounced decline in the testicular levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and MDA, with higher testosterone levels relative to the methanolic extract. Further improvements in the Johnsen score, histopathological results and all biochemical assays were achieved by pre-treatment with the three selected pure compounds kaempferol, quercetin and rutin. In conclusion, <i>M. alysson</i> L. could protect against MTX-induced testicular injury by its antioxidant, anti-inflammatory, antiapoptotic activities and through the regulation of the miRNA-29a testicular expression. The present study also included chemical profiling of <i>M. alysson</i> L. extract, which was accomplished by LC-ESI-TOF-MS/MS analysis. Forty compounds were provisionally assigned, comprising twenty compounds discovered in the positive mode and seventeen detected in the negative mode.https://www.mdpi.com/2223-7747/11/17/2309sustainability of natural resourcesdrug discovery<i>Marrubium alysson</i> L.metabolomic profilingmethotrexatetesticular damage |
| spellingShingle | Reda F. A. Abdelhameed Asmaa I. Ali Sameh S. Elhady Hend E. Abo Mansour Eman T. Mehanna Sarah M. Mosaad Salma A. Ibrahim Rawan H. Hareeri Jihan M. Badr Nermeen A. Eltahawy <i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling Plants sustainability of natural resources drug discovery <i>Marrubium alysson</i> L. metabolomic profiling methotrexate testicular damage |
| title | <i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling |
| title_full | <i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling |
| title_fullStr | <i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling |
| title_full_unstemmed | <i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling |
| title_short | <i>Marrubium alysson</i> L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling |
| title_sort | i marrubium alysson i l ameliorated methotrexate induced testicular damage in mice through regulation of apoptosis and mirna 29a expression lc ms ms metabolic profiling |
| topic | sustainability of natural resources drug discovery <i>Marrubium alysson</i> L. metabolomic profiling methotrexate testicular damage |
| url | https://www.mdpi.com/2223-7747/11/17/2309 |
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