Network pharmacology and molecular modelling study of Enhydra fluctuans for the prediction of the molecular mechanisms involved in the amelioration of nephrolithiasis

Abstract

In view of the ethno medicinal use of Enhydra fluctuans for the treatment of kidney stones; the present study aimed to elucidate the molecular mechanisms involved in the amelioration of nephrolithiasis through a network pharmacology approach. The phytoconstituents were queried in DIGEP-Pred to identify the regulated proteins. The modulated proteins were then enriched in the STRING to predict the protein-protein interactions and the probably regulated pathways were traced in the Kyoto Encyclopedia of Genes and Genomes. Further, the network was constructed using Cytoscape ver 3.5.1. Results showed that β-carotene was found to be regulating maximum targets i.e. 26. In addition, 63 proteins were triggered by the components in which the vitamin D receptor was targeted by the maximum phytoconstituents i.e. 16. The enrichment analysis identified the regulation of 67 pathways in which fluid shear stress and atherosclerosis-associated pathways (KEGG entry hsa05418) regulated ten genes. Further, protein kinase C-α was traced in 23 different pathways. In addition, the majority of the regulated genes were identified from the extracellular space via the modulation of 43 genes. Also, nuclear receptor activity had the maximum molecular function via the regulation of 7 genes. Likewise, the response to organic substance was predicted to trigger the top genes i.e. 43. In contrast, Stigmasterol, Baicalein-7-o-glucoside, and Kauran-16-ol were found to have a high affinity to bind with the VDR receptor confirmed by the molecular modelling and the dynamics. Hence, the study elucidated the probable molecular mechanisms of E. fluctuans in managing nephrolithiasis and identified the lead molecules, their targets, and possible pathways.

Communicated by Ramaswamy H. Sarma

Keywords:

• Enhydra fluctuans
• in silico study
• kidney stones
• nephrolithiasis
• network pharmacology

Acknowledgment

The authors are thankful to Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi for providing facilities for the research work (Project File number SRG/2021/001631).

Authors’ contributions

YND: Conceptualization, Supervision, Formal Analysis, Writing (Review and Editing). BC, PK, AN, AD and AS: Data Collection, Investigation, Writing; SM: Revision.

Consent to participate

All authors agree mutually with the participation in this work and declare that this is original research.

Consent to publish

All authors read and approved the final manuscript for publication.

Disclosure statement

The authors declare there are no conflicts of interest.

Additional information

Funding

This study is supported by Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi (Project File number SRG/2021/001631).