Dataset Information

From seeds to survival rates: investigating Linum usitatissimum's potential against ovarian cancer through network pharmacology.

ABSTRACT: Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan-Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics.

SUBMITTER: Islam MM

PROVIDER: S-EPMC10642394 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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From seeds to survival rates: investigating <i>Linum usitatissimum</i>'s potential against ovarian cancer through network pharmacology.

Islam Mohammed Monirul MM Sreeharsha Nagaraja N Alshabrmi Fahad M FM Asif Afzal Haq AH Aldhubiab Bandar B Anwer Md Khalid MK Krishnasamy Rajendiran R Rehman Abdur A

Frontiers in pharmacology 20231030

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of <i>Linum usitatissimum</i> against ovarian cancer, but the specific molecular mechanisms remain elusive. T ...[more]

PMID: 37964873

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Project description:BackgroundOxidative stress (OS) is one of the major causes of ovarian aging and dysfunction. Indole-3-propionic acid (IPA) is an indole compound derived from tryptophan with free radical scavenging and antioxidant properties, and thus may have potential applications in protecting ovarian function, although the exact mechanisms are unknown. This study aims to preliminarily elucidate the potential mechanisms of IPA that benefit ovarian reserve function through network pharmacology, molecular docking, and experimental verification.MethodsThe related protein targets of IPA were searched on SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. The potential targets of diminished ovarian reserve (DOR) were identified from OMIM, GeneCards, DrugBank, and DisGeNET databases. The common targets were uploaded directly to the STRING database to construct PPI networks. We then performed GO and KEGG enrichment analysis on the targets. Subsequently, molecular docking and molecular dynamics simulation were used to validate the binding conformation of IPA to candidate targets. Furthermore, we carried out in vitro experiments to validate the prediction results of network pharmacology.ResultsWe identified a total of 61 potential targets for the interaction of IPA with DOR. The PPI network topological parameter analysis yielded 13 hub genes for DOR treatment. The GO biological process enrichment analysis identified 293 entries, mainly enriched in aging, signal transduction, response to hypoxia, negative regulation of apoptotic process, and positive regulation of cell proliferation. The KEGG enrichment analysis mainly included lipid and atherosclerosis, progesterone-mediated oocyte maturation, AGE-RAGE, relaxin, estrogen, and other signaling pathways. The molecular docking further revealed the direct binding of IPA with six hub proteins including NOS3, AKT1, EGFR, PPARA, SRC, and TNF. In vitro experiments showed that IPA pretreatment attenuated H2O2-induced cellular oxidative stress damage, while IPA exerted cytoprotective and antioxidant damage effects by regulating the six hub genes and antioxidant proteins.ConclusionWe systematically illustrated the potential protective effects of IPA against DOR through multiple targets and pathways using network pharmacology, and further verified the cytoprotective effect and antioxidant properties of IPA through in vitro experiments. These findings provide new insights into the targets and molecular mechanisms whereby IPA improves DOR.

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Dataset Information

From seeds to survival rates: investigating Linum usitatissimum's potential against ovarian cancer through network pharmacology.

Publications

From seeds to survival rates: investigating <i>Linum usitatissimum</i>'s potential against ovarian cancer through network pharmacology.

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