Unraveling the mechanisms of Fenugreek seed for managing different gynecological disorders: steroidal saponins and isoflavones revealed as key bioactive metabolites

Shawky, Eman; Nassra, Rasha A.; El-Alkamy, Aliaa M.T.; Sallam, Shaimaa M.; El Sohafy, Samah M.

doi:10.1016/j.jpba.2023.115865

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…43 Also, luteolin could increase serum estradiol levels and improve the histological structure of ovaries in lactating female rats. 44 Kaempferol has been shown to have antioxidant effects, scavenge reactive oxygen species (ROS), inhibit apoptosis, and contribute to cellular protection. 45,46 Topological analysis confirmed that MAPK14, MYC, ESR1, IL2, HIF1A, AKT1, STAT1, CDKN1A, MAPK1, EGFR, JUN, and HSP90AA1 were the hub genes associated with ZYBYF treatment of DOR.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and In Vivo Validation to Explore the Potential Active Ingredients and Mechanisms of Ziyin Buyang Formula in Diminished Ovarian Reserve

Wang,

Huang,

et al. 2024

Natural Product Communications

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The incidence rate of diminished ovarian reserve (DOR) is increasing, which is a difficult problem in the field of reproductive biology. The Ziyin Buyang Formula (ZYBYF), an empirical prescription for traditional Chinese medicine, is often used to improve the ovarian function of women with DOR. However, the underlying mechanism of this phenomenon remains unclear. This study was designed to identify the active components of ZYBYF and to further investigate the mechanism by which ZYBYF treats DOR through network pharmacological analysis and in vivo experiments. The network-based relationships between drug targets and disease-related proteins were screened, predicted, and constructed using a database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using R software. AutoDock Vina 1.1.2 was used to perform the molecular docking analysis. In vivo experimental verification was carried out by enzyme-linked immunosorbent assay, histological observation and reverse transcription-polymerase chain reaction. A total of 137 common targets were identified between ZYBYF and DOR. GO and KEGG enrichment analyses suggested that these compounds were associated with the PI3K/AKT signaling pathway and MAPK signaling pathway. Furthermore, the molecular docking analysis revealed that quercetin strongly binds to MAPK1, AKT1, MYC, EGFR, and BCL2; luteolin strongly binds to EGFR, AKT1, and MAPK1; and kaempferol strongly binds to AKT1 and BCL2. In addition, in vivo experiments confirmed that ZYBYF can regulate the serum sex hormone levels, improve the ovarian function of DOR model rats, downregulate the expression of Mapk1 and Mapk14, and increase the levels of Akt1, Egfr, Myc, and Bcl2. ZYBYF improved ovarian function in DOR model rats by regulating the MAPK and PI3K/AKT signaling pathways. This study provides objective evidence that supports the use of ZYBYF in the clinical application of DOR.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology and In Vivo Validation to Explore the Potential Active Ingredients and Mechanisms of Ziyin Buyang Formula in Diminished Ovarian Reserve

Wang,

Huang,

et al. 2024

Natural Product Communications

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“…Although some studies have reported that fenugreek has pharmacological effects on some human diseases [ 24 , 25 ], few reports have comprehensively explored the medicinal compounds present in fenugreek. It was reported that flavones, isoflavones, steroidal saponins, and diosgenin in fenugreek were used in reproductive processes, lactation, estrogenic activity, and diabetes [ 26 , 27 ]. According to our transcriptome and metabolome analyses and previous reports, flavonoids, isoflavonoids, and alkaloids are thought to be important components in fenugreek fruits and should receive increased attention.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic and Transcriptomic Analyses Reveal the Molecular Mechanism Underlying the Massive Accumulation of Secondary Metabolites in Fenugreek (Trigonella foenum-graecum L.) Seeds

Zhao,

Wu,

Yang

et al. 2024

Genes

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Fenugreek (Trigonella foenum-graecum L.) is a traditional medicinal plant for treating human diseases that is widely cultivated in many countries. However, the component and related metabolic pathways are still unclear. To understand the changes in expression of the component and related genes during seed development, this study employed metabolomic and transcriptomic analyses and integrative analysis to explore the metabolites and pathways involved in the growth of fenugreek. The antifungal activity of the fenugreek seeds was also analyzed. A total of 9499 metabolites were identified in the positive ion mode, and 8043 metabolites were identified in the negative ion mode. Among them, the main components were fatty acyls, prenol lipids, steroids, steroid derivatives, flavonoids, and isoflavonoids. Among these enriched pathways, the top 20 pathways were “flavone and flavonol biosynthesis”, “isoflavonoid biosynthesis”, and “flavonoid biosynthesis”. 3,7-Di-O-methylquercetin, flavonoids, pseudobaptigenin, isoflavonoids, methylecgonine, alkaloids, and derivatives were the most significantly upregulated metabolites. There were 38,137 differentially expressed genes (DEGs) identified via transcriptomic analysis. According to the KEGG pathway enrichment analysis, 147 DEGs were significantly enriched in “flavonoid biosynthesis”. Ten DEGs of the six key enzymes were found to be involved in three pathways related to flavonoid and alkaloid synthesis in fenugreek. The antifungal activity test revealed the inhibitory effect of the ethanol extract of fenugreek seeds on Alternaria tenuissima (Kunze)Wiltshire and Magnaporthe oryzae. These findings further prove that the use of botanical pesticides in fenugreek fruit has research value.

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Unraveling the mechanisms of Fenugreek seed for managing different gynecological disorders: steroidal saponins and isoflavones revealed as key bioactive metabolites

Cited by 2 publications

References 45 publications

Network Pharmacology and In Vivo Validation to Explore the Potential Active Ingredients and Mechanisms of Ziyin Buyang Formula in Diminished Ovarian Reserve

Network Pharmacology and In Vivo Validation to Explore the Potential Active Ingredients and Mechanisms of Ziyin Buyang Formula in Diminished Ovarian Reserve

Metabolomic and Transcriptomic Analyses Reveal the Molecular Mechanism Underlying the Massive Accumulation of Secondary Metabolites in Fenugreek (Trigonella foenum-graecum L.) Seeds

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