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Network pharmacology-based anti-colorectal cancer activity of piperlonguminine in the ethanolic root extract of Piper longum L

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Abstract

Colorectal cancer (CRC) has the second highest incidence and fatality rates of any malignancy, at 10.2 and 9.2%, respectively. Plants and plants-based products for thousands of years have been utilized to treat cancer along with other associated health issues. Alkaloids are a valuable class of chemical compounds with great potential as new medicine possibilities. Piper longum Linn contains various types of alkaloids. In this research, the ethanolic root extract of P. longum (EREPL) is the subject of study based on network pharmacology. Two alkaloids were chosen from the gas chromatography mass spectrometry (GC–MS) analysis. However, only piperlonguminine received preference because it adhered to Lipinski's rule and depicted no toxicity. Web tools which are available online, like, Swiss ADME, pkCSMand ProTox-II were used to evaluate the pharmacokinetics and physiochemical properties of piperlonguminine. The database that SwissTargetPrediction and TCMSP maintain contains the targets for piperlonguminine. Using DisGeNET, GeneCards and Open Targets Platform databases, we were able to identify targets of CRC. The top four hub genes identified by Cytoscape are SRC, MTOR, EZH2, and MAPK3. The participation of hub genes in colorectal cancer-related pathways was examined using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The colorectal cancer pathway, the ErbB signaling pathway and the mTOR signaling pathway emerged to be important. Our findings show that the hub genes are involved in the aforementioned pathways for tumor growth, which calls for their downregulation. Additionally, piperlonguminine has the potential to become a successful medicine in the future for the treatment of CRC.

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Data availability

The information that helps to back up the conclusions drawn from this study can be found in public databases.

Abbreviations

GC–MS:

Gas chromatography–mass spectrometry

EREPL:

Ethanolic root extract of Piper longum

KEGG:

Kyoto encyclopedia of genes and genomes

PPI:

Protein–protein interaction

ADME:

Absorption, distribution, metabolism, and excretion

HBD:

Hydrogen bond donor

HBA:

Hydrogen bond acceptor

TPSA:

Topological polar surface area

DL:

Druglikeness

MR:

Molar refractivity

HIA:

Human intestinal absorption

BBB:

Blood–brain barrier

CYP2D6:

CYP2D6 cytochrome P450 2D6

CYP3A4:

Cytochrome P450 3A4

hERG:

Human ether-a-go-go related gene

LOAEL:

Lowest-observed adverse-effect level

TCMSP:

Traditional Chinese medicine systems pharmacology database and analysis platform

STRING:

Search tool for the retrieval of interacting genes/proteins

GO:

Gene ontology

DAVID:

Database for annotation, visualization and integrated discovery

GEPIA:

Gene expression profiling interactive analysis

MW:

Molecular weight

ADMET:

Absorption, distribution, metabolism, excretion, and toxicity

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Acknowledgements

The Fellow Indrajeet Singh thankfully recognized to CSIR, New Delhi and Rama University, Kanpur for given that the amenities to carry out research.

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No government, business, or nonprofit organization provided specific support for this study.

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Engineering and Technology, Rama University, G.T. Road, Mandhana, Kanpur, Uttar Pradesh, 209217, India

    Indrajeet Singh & Ajay Kumar

  2. Department of Biotechnology, Parul Institute of Applied Science, Parul University, Vadodara, Gujarat, 391760, India

    Richa Das

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IS and AK created the idea and layout for the work,which IS, RD, and AK completed gathering information, analyzing it, and interpreting the findings, fractionation, and preparing the manuscript for submission. The manuscript has been read and approved by all of the authors.

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Correspondence to Ajay Kumar.

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Singh, I., Das, R. & Kumar, A. Network pharmacology-based anti-colorectal cancer activity of piperlonguminine in the ethanolic root extract of Piper longum L. Med Oncol 40, 320 (2023). https://doi.org/10.1007/s12032-023-02185-5

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