International Journal of Drug Delivery Technology
Volume 16, Issue 2s

Unraveling Multi-Target Interactions of Nilgirianthus ciliatus (Nees) Bremek. Triterpenoids Against Pulmonary Disease via Network Pharmacology, Docking, and Molecular Dynamics

Pavan Kumar Katukukke1, Collince Omondi Awere2, Venkatramanan Varadharajan3, Manikandan Ramesh4*

1PhD scholar, Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, Tamilnadu-630003, India
orcid id: 0000-0003-2170-144X
2PhD scholar, Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, Tamilnadu-630003, India
orcid id: 0000-0002-7763-0997
3Assistant Professor, Department of Biotechnology, PSG College of Technology, Peelamedu, Coimbatore, India
orcid id: 0000-0002-5608-7737
4*Professor, Department of Biotechnology, PSG College of Technology, Peelamedu, Coimbatore, India
orcid id: 0000-0002-7969-4935

ABSTRACT

Pulmonary inflammation (PI), pulmonary fibrosis (PF), and lung cancer (LC) manifest a progressive disease continuum driven by chronic immune activation, oxidative stress, and aberrant tissue remodeling. Given the limited effectiveness of single-target therapies in modulating these interlinked pathways, plant-derived multi-target compounds represent a plausible therapeutic option. This study systematically explored the multi-target potential of Nilgirianthus ciliatus (Nees) Bremek (NC). phytoconstituents against pulmonary diseases using integrated network pharmacology, molecular docking, toxicity assessment, and molecular dynamics simulations. A total of 821 NC phytocompounds-related genes and over 22,000 disease-associated genes were mined, revealing 157 common molecular targets. Protein–protein interaction analysis revealed STAT3, SRC, JUN, AKT1, and ESR1 as major hub nodes governing inflammatory and fibrotic signaling. GO and KEGG enrichment displayed significant involvement of oxidative stress responses, cytokine signaling, PI3K–Akt, MAPK, TNF, and IL-17 pathways, which indicates molecular relevance to pulmonary injury and remodeling. Docking analysis revealed outstanding STAT3 binding affinities for triterpenoids like lupeol, β-amyrin, and squalene; in particular, squalene was found to possess good stability and predicted low toxicity (Class V). Molecular Dynamic simulation of the STAT3–squalene complex revealed stable binding, with minimal conformational drift and consistent hydrophobic interaction involving key residues, thus indicating sustained inhibitory potential therein. Collectively, these findings underpin the potential of NC terpenoids—especially squalene to modulate multiple pathogenic targets and axes implicated in pulmonary inflammation, fibrosis, and carcinogenesis. This computational evidence positions NC as a promising candidate for further experimental validation and development of multi-target therapeutics against chronic lung disorders.

Keywords: Phytoconstituents; Terpenoids; Multi-target therapy; pulmonary disease; Network pharmacology; Molecular docking.

How to cite this article: Katukukke PK, Awere CO, Varadharajan V, Ramesh M, Unraveling Multi-Target Interactions of Nilgirianthus ciliatus (Nees) Bremek. Triterpenoids Against Pulmonary Disease via Network Pharmacology, Docking, and Molecular Dynamics. Int J Drug Deliv Technol. 2026;16(2s): 897-908; DOI: 10.25258/ijddt.16.897-908