Network pharmacology and molecular docking study for biological pathway detection of cytotoxicity of the yellow jasmine flowers.

BACKGROUND: The yellow jasmine flower (Jasminum humile L.) is a fragrant plant belonging to the Oleaceae family with promising phytoconstituents and interesting medicinal uses. The purpose of this study was to characterize the plant metabolome to identify the potential bioactive agents with cytotoxic effects and the underlying mechanism of cytotoxic activity. METHODS: First, HPLC-PDA-MS/MS was used to identify the potential bioactive compounds in the flowers. Furthermore, we assessed the cytotoxic activity of the flower extract against breast cancer (MCF-7) cell line using MTT assay followed by the cell cycle, DNA-flow cytometry, and Annexin V-FITC analyses alongside the effect on reactive oxygen species (ROS). Finally, Network pharmacology followed by a molecular docking study was performed to predict the pathways involved in anti-breast cancer activity. RESULTS: HPLC-PDA-MS/MS tentatively identified 33 compounds, mainly secoiridoids. J. humile extract showed a cytotoxic effect on MCF-7 breast cancer cell line with IC50 value of 9.3 ± 1.2 µg/mL. Studying the apoptotic effect of J. humile extract revealed that it disrupts G2/M phase in the cell cycle, increases the percentage of early and late apoptosis in Annexin V-FTIC, and affects the oxidative stress markers (CAT, SOD, and GSH-R). Network analysis revealed that out of 33 compounds, 24 displayed interaction with 52 human target genes. Relationship between compounds, target genes, and pathways revealed that J. humile exerts its effect on breast cancer by altering, Estrogen signaling pathway, HER2, and EGFR overexpression. To further verify the results of network pharmacology, molecular docking was performed with the five key compounds and the topmost target, EGFR. The results of molecular docking were consistent with those of network pharmacology. CONCLUSION: Our findings suggest that J. humile suppresses breast cancer proliferation and induces cell cycle arrest and apoptosis partly by EGFR signaling pathway, highlighting J. humile as a potential therapeutic candidate against breast cancer.

Protective effects of Balanites aegyptiaca extract, Melatonin and Ursodeoxycholic acid against hepatotoxicity induced by Methotrexate in male rats.

OBJECTIVE: To compare the degree of ameliorative effects of Melatonin (MEL), Ursodeoxycholic acid (UDCA) and Balanites aegyptiaca (BA) against hepatotoxicity induced by MTX for one month. METHODS: Eighty adult male rats (Sprague Dawely) weighing (190 ± 10 g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX + MEL, MTX + BA, MTX + UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor (TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. RESULTS: MTX showed significant increase in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione (GSSG), malodialdehyde (MDA) and nitric oxide (NO). Whereas total protein, albumin, total antioxidant capacity, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. CONCLUSIONS: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.