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Network pharmacology-based study on apigenin present in the methanolic fraction of leaves extract of Cestrum nocturnum L. to uncover mechanism of action on hepatocellular carcinoma

Medical Oncology volume 39, Article number: 155 (2022) Cite this article

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer in the world. It is the third leading cause of cancer-related mortality. In more than 80% of people liver cancer-related death is due to its poor prognosis. The flavonoids obtained from natural sources have potent therapeutic effects on HCC. The flavonoid rich methanolic fraction obtained from ethyl acetate extract of leaf of Cestrum nocturnum (MFLCN) was analyzed by UPLC-QTOFMS/MS for the presence of different flavonoids. The physiochemical and pharmacokinetics properties of the identified flavonoids were performed by absorption, distribution, metabolism, excretion, and toxicity (ADMET). It was selected on the basis of Lipinski rule and hepatotoxicity evaluations. The potential gene dataset of HCC were taken from gene card database and targets compounds were selected from target net prediction. Gene ontology and pathway enrichment analysis of HCC was performed via enricher and David web tools. Cytoscape was used to visualize targets and network pathways. MFLCN contains 33 flavonoids. Among these flavonoids, apigenin was selected as principal active compound on the basis of their pharmacokinetic and ADMET properties. Apigenin has 92 targets out of 627 total targets related to HCC, while there was13 pathways in the target-pathway network. Results revealed that apigenin regulates cell proliferation and survival, primarily through different signaling pathways like estrogen, VEGF, PI3K/AKT1, TNF, FoXO, and Ras signaling pathways. Thus, integrating network pharmacology prediction with m-RNA and human protein atlas validation could be an effective method for understanding the molecular mechanism of apigenin on HCC.

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Data availability

The data that support the findings of this study are available from public databases.

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Acknowledgements

The author Pradeep Kumar gratefully acknowledged to UGC, New Delhi (F-1-17-1/2014-15/RGNF-2014-15-SC-UTT-58260) for financial support as a JRF and SRF. Author Kavindra Nath Tiwari acknowledges to Institute of Eminence (IoE) Banaras Hindu University, Varanasi, India for financial support for research work (Scheme No.6031).

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This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Botany, MMV, Banaras Hindu University, Varanasi, 221005, UP, India

    Pradeep Kumar, Pooja Verma & Kavindra Nath Tiwari

  2. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005, UP, India

    Amit Kumar Singh & Sunil Kumar Mishra

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  1. Pradeep Kumar
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KNT and SKM: developed the concept and design of work, PK and AKS: Data collection, analysis and interpretation of results, PV: fractionation and manuscript preparation.

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Correspondence to Kavindra Nath Tiwari.

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Kumar, P., Singh, A.K., Verma, P. et al. Network pharmacology-based study on apigenin present in the methanolic fraction of leaves extract of Cestrum nocturnum L. to uncover mechanism of action on hepatocellular carcinoma. Med Oncol 39, 155 (2022). https://doi.org/10.1007/s12032-022-01759-z

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  • DOI: https://doi.org/10.1007/s12032-022-01759-z

Keywords

  • Hepatocellular carcinoma (HCC)
  • UPLC-QTOFMS/MS
  • Hub gene
  • ADMET
  • MFLCN