QSAR, docking and in vivo studies for immunomodulatory activity of isolated triterpenoids from Eucalyptus tereticornis and Gentiana kurroo

Two triterpenoids ursolic acid (1) and lupeol (2) isolated and characterized from Eucalyptus tereticornis and Gentiana kurroo were subjected to in silico QSAR modeling and docking studies and later the predicted results were confirmed through in vivo experiments. QSAR modeling results showed that both the triterpenoids possess immunomodulatory and anti-inflammatory activity comparable to boswellic and cichoric acids, but were less active than levamisol. Docking results suggested that both the triterpenoids (1 and 2) showed immune modulatory and anti-inflammatory activity due to high binding affinity to human receptors viz., NF-kappaB p52 (−50.549 kcal/mol), tumor necrosis factor (TNF-alpha) (−47.632 kcal/mol), nuclear factor NF-Kappa-B P50 (−16.798 kcal/mol) and cyclooxygenase-2 (−55.244 kcal/mol). Further both the triterpenoids (1 and 2) were subjected to in vivo immunomodulatory activity in female Swiss albino mice. The experimental mice were divided into nine groups, each comprised of six mice. These received oral treatment for a period of 28 days. The triterpenoids (1 and 2) showed significant increased in humoral immune function, but no significant changes were observed in cell mediated immune response and hematological parameters. The in silico and in vivo experimental data suggested that both the triterpenoids 1 and 2 may be considered as potential immunomodulatory drug-like molecules.

Lupeol (7, triterpenoid-2) docked on cyclooxygenase (1CX2) receptor with high affinity docking score −49.433 kcal/mol.Figure optionsDownload high-quality image (81 K)Download as PowerPoint slide