Testicular caspase-3 and β-catenin regulators predicted via comparative metabolomics and docking studies

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

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Abstract

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 LD50 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 Albizzia lebbeck was the most active extract for decreasing immunoexpression of β-catenin, while Rosmarinus officinalis showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of A. lebbeck, Anagallis arvensis, and R. officinalis can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells.

Original languageEnglish
Article number31
Number of pages23
JournalMetabolites
Volume10
Issue number1
DOIs
Publication statusPublished - 11 Jan 2020

Fingerprint

Catenins
Metabolomics
Caspase 3
Plant Extracts
Rosmarinus
Saponins
Spermatogenesis
Anagallis
Testis
Female Contraceptive Agents
Albizzia
Immunohistochemistry
Triterpenes
Passive Cutaneous Anaphylaxis
Organ Size
Diterpenes
Sperm Motility
Lethal Dose 50
Gonadal Steroid Hormones
Phytochemicals

Keywords

  • Testicular spermatogenesis
  • β-catenin
  • Caspase-3
  • Albizzia lebbeck
  • Anagallis arvensis
  • Rosmarinus officinalis
  • Metabolomic profiling
  • Docking

Cite this

Hifnawy, M. S., Aboseada, M. A., Hassan, H. M., AboulMagd, A. M., Tohamy, A. F., Abdel-Kawi, S. H., ... Abdelmohsen, U. R. (2020). Testicular caspase-3 and β-catenin regulators predicted via comparative metabolomics and docking studies. Metabolites, 10(1), [31]. https://doi.org/10.3390/metabo10010031
Hifnawy, Mohammed S. ; Aboseada, Mahmoud A. ; Hassan, Hossam M. ; AboulMagd, Asmaa M. ; Tohamy, Adel F. ; Abdel-Kawi, Samraa H. ; Rateb, Mostafa E. ; El Naggar, El Moataz Bellah ; Liu, Miaomiao ; Quinn, Ronald J. ; Alhadrami, Hani A. ; Abdelmohsen, Usama Ramadan. / Testicular caspase-3 and β-catenin regulators predicted via comparative metabolomics and docking studies. In: Metabolites. 2020 ; Vol. 10, No. 1.
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Hifnawy, MS, Aboseada, MA, Hassan, HM, AboulMagd, AM, Tohamy, AF, Abdel-Kawi, SH, Rateb, ME, El Naggar, EMB, Liu, M, Quinn, RJ, Alhadrami, HA & Abdelmohsen, UR 2020, 'Testicular caspase-3 and β-catenin regulators predicted via comparative metabolomics and docking studies', Metabolites, vol. 10, no. 1, 31. https://doi.org/10.3390/metabo10010031

Testicular caspase-3 and β-catenin regulators predicted via comparative metabolomics and docking studies. / Hifnawy, Mohammed S.; Aboseada, Mahmoud A.; Hassan, Hossam M.; AboulMagd, Asmaa M.; Tohamy, Adel F.; Abdel-Kawi, Samraa H.; Rateb, Mostafa E.; El Naggar, El Moataz Bellah; Liu, Miaomiao; Quinn, Ronald J.; Alhadrami, Hani A.; Abdelmohsen, Usama Ramadan.

In: Metabolites, Vol. 10, No. 1, 31, 11.01.2020.

Research output: Contribution to journalArticle

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AU - Hifnawy, Mohammed S.

AU - Aboseada, Mahmoud A.

AU - Hassan, Hossam M.

AU - AboulMagd, Asmaa M.

AU - Tohamy, Adel F.

AU - Abdel-Kawi, Samraa H.

AU - Rateb, Mostafa E.

AU - El Naggar, El Moataz Bellah

AU - Liu, Miaomiao

AU - Quinn, Ronald J.

AU - Alhadrami, Hani A.

AU - Abdelmohsen, Usama Ramadan

PY - 2020/1/11

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N2 - 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 LD50 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 Albizzia lebbeck was the most active extract for decreasing immunoexpression of β-catenin, while Rosmarinus officinalis showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of A. lebbeck, Anagallis arvensis, and R. officinalis can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells.

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KW - Albizzia lebbeck

KW - Anagallis arvensis

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KW - Metabolomic profiling

KW - Docking

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Hifnawy MS, Aboseada MA, Hassan HM, AboulMagd AM, Tohamy AF, Abdel-Kawi SH et al. Testicular caspase-3 and β-catenin regulators predicted via comparative metabolomics and docking studies. Metabolites. 2020 Jan 11;10(1). 31. https://doi.org/10.3390/metabo10010031