Computational Investigation of Phyllanthus niruri Phytoconstituents Against Iron Homeostasis and Thalassemia-Associated Molecular Targets Using Molecular Docking and Network Pharmacology

Abstract

Thalassemia is a hereditary condition that affects haemoglobin formation, leading to ineffective erythropoiesis, anaemia, and iron overload, resulting in serious complications and reduced quality of life. While modern medical care, such as blood transfusions and iron chelation, has considerably extended patients' lifespan, prolonged therapy has been accompanied by various side effects, financial burden, and low compliance. In addition, due to the complex pathogenesis of thalassemia, which includes oxidative stress, inflammation, disrupted iron homeostasis, and cellular damage, there is a need to develop new methods that can address all these processes simultaneously. This fact has led researchers to show great interest in plant-based remedies containing naturally active biological substances. In this study, we explored the therapeutic efficacy of the plant Phyllanthus niruri by investigating its association with target proteins and biological pathways related to iron homeostasis in thalassemic patients, employing a comprehensive bioinformatics approach. Active compounds found in Phyllanthus niruri were recognized and filtered. Then, target identification, along with disease-gene associations, was performed for common diseases and compounds. For biological insights, targets associated with thalassemia and phytoconstituents were analysed employing network pharmacology, protein-protein interaction networks, Gene Ontology enrichment, and KEGG pathway analyses. In vitro molecular docking experiments to predict interactions between phytoconstituents and their targets were performed, and ADMET analysis was conducted to assess pharmacokinetics and drug likeness. Among the identified hub genes were those associated with iron metabolism, oxidative stress, inflammation, and erythrocyte formation. The pathways enriched in the functional enrichment analysis included those associated with iron metabolism, cytokine signalling, apoptosis, and cellular responses to stress. The molecular docking study revealed favourable interactions between the phytoconstituents, particularly corilagin, geraniin, and quercetin, and the target proteins. ADMET predictions indicated favourable pharmacokinetics for some compounds. All in all, the results demonstrate the multitarget potential of Phyllanthus niruri as an important source of bioactive substances that can address complications of thalassemia, especially in cases of iron overload. The study lays an important foundation for the subsequent experimental verification of the results.