Exploring the therapeutic potential of Rhododendron anthopogon D.Don essential oil constituents against lung cancer: A network pharmacology-based analysis with molecular docking and experimental studies

Abstract

Rhododendron anthopogon D.Don is an evergreen shrub used by Himalayan healers to treat many ailments most notably lung problems. However, the mechanism by which R. anthopogon essential oil fights lung cancer has not been well studied. Here, in the present study, we used network pharmacology in combination with chemical profiling, molecular docking, and in-vitro experimental studies to uncover the mechanism of R. anthopogon essential oil constituents against lung cancer. By employing network pharmacology-based analysis, a total of 266 potential target genes obtained for 12 active components of R. anthopogon interacted with 260 common targets and 17,731 disease targets associated with lung cancer were retrieved. Using protein-protein interaction network (PPI), search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization, and integrated discovery (DAVID) databases, we predicted that the main signaling pathways involved in the association of lung cancer with R. anthopogon essential oil constituents are the cancer signaling pathway and vascular endothelial growth factor and its receptor (VEGFR) cancer signalling pathway. Using TIMER 2.0 analysis and University of Alabama Cancer Database (UALCAN) findings, the expression pattern of EGFR was investigated across all TCGA (The cancer genome atlas) datasets. The study revealed that EGFR expression was elevated in various cancers especially in lung adenocarcinoma. Molecular docking analysis revealed that linalool, α-bisabolol, and guaiol possessed strong binding affinity with TNF-α, MAPK3, and EGFR protein drug targets. Our results predicted that TNF-α, MAPK3, and EGFR may be potential molecular targets of R. anthopogon essential oil constituents for the treatment of lung cancer. Furthermore, our study verified that R. anthopogon essential oil constituents inhibit proliferation, and induces apoptosis in lung cancer cell lines. Therefore, the present study highlights anti-lung cancer activity of the constituents of R. anthopogon essential oil and its potential involvement in comprehending therapeutic mechanism that may be applied in the lung cancer therapy.

Keywords: Anti-lung cancer activity; GC/MS; Lung cancer; Molecular docking; Network pharmacology; Rhododendron anthopogon.