Prediction of Nephrolepis cordifolia (L.) K. Presl Mechanism as Hyperlipidemia Using Network Pharmacology, Docking and DFT Method

Samsul Hadi1*, Deni Setiawan2, Noer Komari3, Askur Rahman4, Kunti Nastiti5

1Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Lambung Mangkurat University, Banjarbaru, South Kalimantan, Indonesia, 70714
3Department of Chemistry, Faculty of Mathematics and Natural Sciences, Lambung Mangkurat University, Banjarbaru, South Kalimantan, Indonesia, 70714
4Departement Agricultural Industrial Technology, Faculty of Agriculture, Trunojoyo Madura Universiy, Bankalan, East Java, Indonesia, 69162
5Department of Pharmacy, Faculty of Health, Sari Mulia University, Banjarmasin, South Kalimantan, Indonesia, 70127

Received: 11th Sep, 2025; Revised: 28th Oct 2025; Accepted: 5th Nov, 2025; Available Online: 1st December, 2025

ABSTRACT

As the prevalence of hyperlipidemia, a major risk factor for cardiovascular disease, continues to rise, there is a pressing need for safer and more effective alternative treatments. The molecular mechanism by which Nephrolepis cordifolia (L.) K. Presl exerts its antihyperlipidemic action is unknown, however reports of this activity have been made. Using a mix of network pharmacology, molecular docking, and density functional theory (DFT) analysis, this study sought to explain how active chemicals in N. cordifolia against hyperlipidemia work. Various methods were employed, such as pharmacophore- and Lipinski-based active compound selection, disease prediction using bioinformatics databases, protein-protein interaction (PPI) analysis, Enrichr signaling pathway screening, and docking and density-functional theory (DFT) against the primary target proteins. Seven compounds out of sixty-two made it through the selection process, according to the results. Additionally, ellagic acid, gallic acid, and 6-methyl-2-pyridinemethanol were the three primary chemicals that had the most promise for interacting with hyperlipidemia target proteins, including EGFR, AKT1, and IGF1R. Based on DFT studies, ellagic acid exhibited the lowest HOMO-LUMO energy and docking score of any of these molecules, suggesting the strongest affinity and most stable contact. According to the signal pathway analysis, the compound's mode of action was largely influenced by the following pathways: endocrine resistance, PI3K-Akt, and MAPK signaling, all of which are involved in regulating lipid metabolism. Through the appropriate multi-target molecular processes, this work demonstrates that N. cordifolia may be a natural source of therapy for hyperlipidemia.

Keywords: Hiperlipidemia, Nephrolepis cordifolia, network pharmacology, molecular docking, DFT

How to cite this article: Hadi S, Setiawan D, Komari N, Rahman A, Nastiti K, Prediction of Nephrolepis cordifolia (L.) K. Presl Mechanism as Hyperlipidemia Using Network Pharmacology, Docking and DFT Method. Int J Drug Deliv Technol. 2026;16(1): 352-360. DOI: 10.25258/ijddt.16.1.38