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.

Marine sponges create a wide range of bioactive secondary metabolites, as documented throughout the year. Several bioactive secondary metabolites were isolated from different members of Callyspongia siphonella species. This study aimed for isolation and structural elucidation of major metabolites in order to investigate their diverse bioactivities such as antimicrobial and anti-biofilm activities. Afterwards, a molecular docking study was conducted, searching for the possible mechanistic pathway of the most bioactive metabolites. Extraction, fractionation, and metabolomics analysis of different fractions was performed in order to obtain complete chemical profile. Moreover, in vitro assessment of different bioactivities was performed, using recent techniques. Additionally, purification, structural elucidation of high features using recent chromatographic and spectroscopic techniques was established. Finally, AutoDock Vina software was used for the Pharmacophore-based docking-based analysis. As a result, DCM (dichloromethane) fraction exerted the best antibacterial activity using disc diffusion method; particularly against S. aureus with an inhibition zone of 6.6 mm. Compound 11 displayed a considerable activity against both MRSA (Methicillin-resistant Staphyllococcus aureus) and Staphyllococcus aureus with inhibition ratios of 50.37 and 60.90%, respectively. Concerning anti-biofilm activity, compounds 1 and 2 displayed powerful activity with inhibition ratios ranging from 39.37% to 70.98%. Pharmacophore-based docking-based analysis suggested elongation factor G (EF-G) to be a probable target for compound 11 (siphonellinol C) that showed the best in vitro antibacterial activity, offering unexplored potential for new drugs and treatment candidates.

Origanum majoranum L. is a Lamiaceae medicinal plant with culinary and ethnomedical applications. Its biological and phytochemical profiles have been extensively researched. Accordingly, this study aimed to investigate the chemical composition and the antibacterial and antioxidant properties of O. majoranum high features, as well as to search for techniques for activity optimization. A metabolomics study of the crude extract of O. majoranum using liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC ± HR ± ESI ± MS) was conducted. Five fractions (petroleum ether, dichloromethane, ethyl acetate, n-butanol, and aqueous) were derived from the total extract of the aerial parts. Different chromatographic methods and NMR analysis were utilized to purify and identify the isolated phenolics (high features). Moreover, the antimicrobial, antibiofilm, and antioxidant activity of phenolics were performed. Results showed that metabolomic profiling of the crude extract of O. majoranum aerial parts revealed the presence of a variety of phytochemicals, predominantly phenolics, resulting in the isolation and identification of seven high-feature compounds comprising two phenolic acids, rosmarinic and caffeic acids, one phenolic diterpene, 7-methoxyepirosmanol, in addition to four flavonoids, quercetin, hesperitin, hesperidin, and luteolin. On the other hand, 7-methoxyepirosmanol (OM₁) displayed the most antimicrobial and antioxidant potential. Such a phenolic principal activity improvement seems to be established after loading on gold nanoparticles.

The anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV–vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and anti-biofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli. In conclusion, depending on their bioactive metabolites, P. lamellosa-derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads.