In silico Decoding of the Antidiabetic Potential of Sphaeranthus indicus Linn.: A Network Pharmacology and Molecular Docking Integration

Abstract

Diabetes mellitus is a chronic disease that leads to persistent high blood sugar along with dysfunction of various metabolic systems. Though effective, the latest drug therapies still have some problems like causing side effects and not being able to stop the progression of the loss of cell mass. To study the anti-diabetic potential of Sphaeranthus indicus Linn., a plant that is highly valued in Ayurvedic medicine, this research employs a computational framework linking network pharmacology, molecular docking, and ADME analysis. Screening showed 57 phytochemicals of which 14 significantly interacted with 123 genes associated with Type 2 Diabetes. Through network analysis, the central hub genes ACE, GSK3B, PTGS2, and PTPN1 were identified. 1-triacontanol and beta-sitosterol, two compounds from molecular docking, were found to have strong binding affinity to the major targets PPARgamma, GSK3beta, and ACE with the former having a comparable or even better affinity than the reference drug rosiglitazone. Besides, they exhibited high binding potential for EphA4, which might unveil a pathway for the control of hyperglucagonemia. ADME analysis showed these lead compounds to be drug-like candidates but with a caveat of somewhat limited solubility. These results justify the use of S. indicus as an effective multi, target medicine for not only diabetes but also its vascular complications at the molecular level.

Keywords: Ayurveda; Diabetes Mellitus; In silico; Reverse Pharmacology; Sphaeranthus indicus