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Network pharmacology-based anti-pancreatic cancer potential of kaempferol and catechin of Trema orientalis L. through computational approach

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Abstract

In pancreatic cancer, healthy cells in the pancreas begin to malfunction and proliferate out of control. According to our conventional knowledge, many plants contain several novel bioactive compounds, having pharmaceutical applications for the treatment of disease like pancreatic cancer. The methanolic fraction of fruit extract of Trema orientalis L. (MFETO) was analysed through HRMS. In this in silico study, pharmacokinetic and physicochemical properties of the identified flavonoids from MFETO were screened out by ADMET analysis. Kaempferol and catechin followed Lipinski rules and showed no toxicity in Protox II. Targets of these compounds were taken from SwissTarget prediction and TCMSP whilst targets for pancreatic cancer were taken from GeneCards and DisGeNET databases. The protein–protein interaction (PPI) network of common genes was generated through STRING and then exported to the Cytoscape to get top 5 hub genes (AKT1, SRC, EGFR, TNF, and CASP3). The interaction between compounds and hub genes was analysed using molecular docking, and high binding affinity between them can be visualised by Biovia discovery studio visualizer. Our study shows that, five hub genes related to pancreatic cancer play an important role in tumour growth induction, invasion and migration. Kaempferol effectively check cell migration by inhibiting ERK1/2, EGFR-related SRC, and AKT pathways by scavenging ROS whilst catechin inhibited TNFα-induced activation and cell cycle arrest at G1 and G2/M phases by induction of apoptosis of malignant cells. Kaempferol and catechin containing MFETO can be used for formulation of potent drugs for pancreatic cancer treatment in future.

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Acknowledgements

The author Shreni Agrawal gratefully acknowledged to Department of Pharmaceutical Engineering and Technology, Indian Institute of technology, Banaras Hindu University and Parul Institute of Applied science, Parul University for their immense support.

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

    Shreni Agrawal, Richa Das & Indrani Bhattacharya

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

    Amit Kumar Singh & Sunil Kumar Mishra

  3. School of Basic and Applied Science, Galgotias University, Gautam Budha Nagar, Greater Noida, 203201, UP, India

    Amit Kumar Tripathi

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

    Pradeep Kumar, Praveen Kumar Shukla & Kavindra Nath Tiwari

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SKM, PK and AKS developed the concept and design of work, SA, and RD: Data collection, analysis, interpretation of results and manuscript preparation, IB and PKS: Methodology and fractionation, AKT and KNT: Manuscript review.

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Correspondence to Sunil Kumar Mishra.

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Agrawal, S., Das, R., Singh, A.K. et al. Network pharmacology-based anti-pancreatic cancer potential of kaempferol and catechin of Trema orientalis L. through computational approach. Med Oncol 40, 133 (2023). https://doi.org/10.1007/s12032-023-01996-w

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