Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies
Many routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of ten di...
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MDPI AG
2020-01-01
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| author | Mohammed S. Hifnawy Mahmoud A. Aboseada Hossam M. Hassan Asmaa M. AboulMagd Adel F. Tohamy Samraa H. Abdel-Kawi Mostafa E. Rateb El Moataz Bellah El Naggar Miaomiao Liu Ronald J. Quinn Hani A. Alhadrami Usama Ramadan Abdelmohsen |
| author_facet | Mohammed S. Hifnawy Mahmoud A. Aboseada Hossam M. Hassan Asmaa M. AboulMagd Adel F. Tohamy Samraa H. Abdel-Kawi Mostafa E. Rateb El Moataz Bellah El Naggar Miaomiao Liu Ronald J. Quinn Hani A. Alhadrami Usama Ramadan Abdelmohsen |
| author_sort | Mohammed S. Hifnawy |
| collection | DOAJ |
| description | Many routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of ten different plant extracts on testicular spermatogenesis. The correlation between the chemical profile of these extracts and their in vivo effect on male reproductive system was evaluated using various techniques. Approximately 10% of LD<sub>50</sub> of hydro-methanolic extracts were orally administrated to rats for 60 days. Semen parameters, sexual organ weights, and serum levels of male sex hormones in addition to testes histopathology, were evaluated. Moreover, metabolomic analysis using (LC-HRESIMS), multivariate analysis (PCA), immunohistochemistry (caspase-3 and β-catenin), and a docking study were performed. Results indicated that three plant extracts significantly decreased epididymal sperm density and motility. Moreover, their effects on testicular cells were also assured by histopathological evaluations. Metabolomic profiling of the bioactive plant extracts showed the presence of diverse phytochemicals, mostly oleanane saponins, phenolic diterpenes, and lupane triterpenes. A docking study on caspase-3 enzyme showed that oleanane saponins possessed the highest binding affinity. An immunohistochemistry assay on β-catenin and caspase-3 indicated that <i>Albizzia lebbeck</i> was the most active extract for decreasing immunoexpression of β-catenin, while <i>Rosmarinus officinalis</i> showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of <i>A. lebbeck, Anagallis arvensis,</i> and <i>R. officinalis</i> can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells. |
| first_indexed | 2024-12-10T13:44:40Z |
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| spelling | doaj.art-1e22866e291348a080df2527e14c15282022-12-22T01:46:29ZengMDPI AGMetabolites2218-19892020-01-011013110.3390/metabo10010031metabo10010031Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking StudiesMohammed S. Hifnawy0Mahmoud A. Aboseada1Hossam M. Hassan2Asmaa M. AboulMagd3Adel F. Tohamy4Samraa H. Abdel-Kawi5Mostafa E. Rateb6El Moataz Bellah El Naggar7Miaomiao Liu8Ronald J. Quinn9Hani A. Alhadrami10Usama Ramadan Abdelmohsen11Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11865, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62513, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, EgyptDepartment of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Cairo 11865, EgyptDepartment of Medical Histology and Cell Biology, Faculty of Medicine, Beni-Suef University, Beni-Suef 62513, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62513, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Damanhur University, Elbehira 22511, EgyptGriffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, AustraliaFaculty of Applied Medical Sciences, Department of Medical Laboratory Technology, King Abdulaziz University, P. O. Box 80402, Jeddah 21589, Saudi ArabiDepartment of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, EgyptMany routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of ten different plant extracts on testicular spermatogenesis. The correlation between the chemical profile of these extracts and their in vivo effect on male reproductive system was evaluated using various techniques. Approximately 10% of LD<sub>50</sub> of hydro-methanolic extracts were orally administrated to rats for 60 days. Semen parameters, sexual organ weights, and serum levels of male sex hormones in addition to testes histopathology, were evaluated. Moreover, metabolomic analysis using (LC-HRESIMS), multivariate analysis (PCA), immunohistochemistry (caspase-3 and β-catenin), and a docking study were performed. Results indicated that three plant extracts significantly decreased epididymal sperm density and motility. Moreover, their effects on testicular cells were also assured by histopathological evaluations. Metabolomic profiling of the bioactive plant extracts showed the presence of diverse phytochemicals, mostly oleanane saponins, phenolic diterpenes, and lupane triterpenes. A docking study on caspase-3 enzyme showed that oleanane saponins possessed the highest binding affinity. An immunohistochemistry assay on β-catenin and caspase-3 indicated that <i>Albizzia lebbeck</i> was the most active extract for decreasing immunoexpression of β-catenin, while <i>Rosmarinus officinalis</i> showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of <i>A. lebbeck, Anagallis arvensis,</i> and <i>R. officinalis</i> can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells.https://www.mdpi.com/2218-1989/10/1/31testicular spermatogenesisβ-catenincaspase-3<i>albizzia lebbeck</i><i>anagallis arvensis</i><i>rosmarinus officinalis</i>metabolomic profilingdocking |
| spellingShingle | Mohammed S. Hifnawy Mahmoud A. Aboseada Hossam M. Hassan Asmaa M. AboulMagd Adel F. Tohamy Samraa H. Abdel-Kawi Mostafa E. Rateb El Moataz Bellah El Naggar Miaomiao Liu Ronald J. Quinn Hani A. Alhadrami Usama Ramadan Abdelmohsen Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies Metabolites testicular spermatogenesis β-catenin caspase-3 <i>albizzia lebbeck</i> <i>anagallis arvensis</i> <i>rosmarinus officinalis</i> metabolomic profiling docking |
| title | Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies |
| title_full | Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies |
| title_fullStr | Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies |
| title_full_unstemmed | Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies |
| title_short | Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies |
| title_sort | testicular caspase 3 and β catenin regulators predicted via comparative metabolomics and docking studies |
| topic | testicular spermatogenesis β-catenin caspase-3 <i>albizzia lebbeck</i> <i>anagallis arvensis</i> <i>rosmarinus officinalis</i> metabolomic profiling docking |
| url | https://www.mdpi.com/2218-1989/10/1/31 |
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