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  • Title: Unraveling the mechanisms of Fenugreek seed for managing different gynecological disorders: steroidal saponins and isoflavones revealed as key bioactive metabolites.
    Author: Shawky E, Nassra RA, El-Alkamy AMT, Sallam SM, El Sohafy SM.
    Journal: J Pharm Biomed Anal; 2024 Jan 20; 238():115865. PubMed ID: 38000191.
    Abstract:
    This study employed network pharmacology-based analysis and reverse molecular docking to investigate the molecular targets and pathways associated with gynecological disorders, particularly those related to steroidal hormones and their receptors, and the potential therapeutic effects of fenugreek (Trigonella foenum-graecum L.) constituents. The STITCH 5.0 database was utilized to identify potential molecular targets, and a compound-target network was constructed. The main targets associated with gynecological disorders included estrogen receptor beta (ESR2), estrogen-related receptor gamma (GPER1), oxytocin receptor (OXTR), progesterone receptor (PGR), prolactin receptor (PRLR), and several enzymes involved in sex hormone biosynthesis. Additionally, network topological analysis revealed that specific compounds, such as quercetin, luteolin, genistein, and vitexin, had significant interactions with the identified targets. Reverse molecular docking analysis confirmed the interactions between the identified compounds and target proteins where quercetin, luteolin, genistein, 4'-methylgenistein, trigoneoside IIB, diosgenin, and vitexin possessed the highest combined docking scores, indicating their multi-target nature. The results highlighted the potential of steroidal saponins, isoflavones, and flavones as active constituents of fenugreek with implications for lactation, reproductive processes, and estrogenic activity. The chemical profiling of saponin-enriched and flavonoid-enriched fractions using UPLC/MS/MS further supported the presence of these bioactive compounds. In an animal model study, the steroidal saponins-enriched fraction of fenugreek seed exhibited a significant increase in the body weight of lactating female rats and serum prolactin levels while the flavonoids-enriched fraction showed an increase in serum estradiol levels and improved the histological structure of ovaries.
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