Drug metabolism and personalized therapy · 2025
Pharmaco-informatics screening of Zingiber officinale biomolecules targeting FOXO6 for chronic kidney disease therapy.
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Kabilan Shanmugampillai Jeyarajaguru, Kunjiappan Selvaraj, Pavadai Parasuraman, Sankaranarayanan Murugesan, Sundar Krishnan
Аннотация
OBJECTIVES: Ginger, scientifically known as Zingiber officinale, is a plant root that has a variety of therapeutic applications, including the treatment of nausea, inflammation, digestive problems, and management of renal function in chronic kidney disease (CKD). CKD is a life-threatening condition that, if untreated, leads to organ damage and is acknowledged as a global health concern. The present study aims at predicting bioactive compounds from Z. officinale that were identified through gas chromatography-mass spectroscopy (GC-MS), with the potential against a selected target of CKD, and was investigated using a pharmaco-informatics approach.
METHODS: The compounds from GC-MS analysis were screened, and the structures of identified compounds were drawn through ACD/Chemsketch 2021.2.1. Based on graph theoretical network analysis, forkhead box protein (FOXO6) was chosen as a potential target for CKD. The Swiss model was used to predict the structure of FOXO6, and the active site details were obtained. Docking was performed against the active sites of FOXO6 using 22 compounds, along with the standard drug, dapagliflozin. Pharmacokinetic, physicochemical and toxicity parameters were predicted for the selected high binders and dapagliflozin. The stability and intermolecular interactions of high binders and dapagliflozin protein-ligand complexes were studied using molecular dynamics simulation.
RESULTS: The binding affinity ranges from -3.5 to -6.7 kcal × mol-1. Abietic acid and dehydroabietic acid had a higher binding affinity with a score of -6.7 kcal × mol-1, similar to the standard drug, dapagliflozin (-6.4 kcal × mol-1). Both abietic acid and dehydroabietic acid also have good bioavailability scores. MD simulation studies indicated greater stability for abietic acid-FOXO6 and dehydroabietic acid-FOXO6 complexes.
CONCLUSIONS: This investigation has shed light on the significance of the compounds of Z. officinale R. as potential FOXO6 inhibitors, which could further be used as a lead compound for developing alternative therapy for CKD.
METHODS: The compounds from GC-MS analysis were screened, and the structures of identified compounds were drawn through ACD/Chemsketch 2021.2.1. Based on graph theoretical network analysis, forkhead box protein (FOXO6) was chosen as a potential target for CKD. The Swiss model was used to predict the structure of FOXO6, and the active site details were obtained. Docking was performed against the active sites of FOXO6 using 22 compounds, along with the standard drug, dapagliflozin. Pharmacokinetic, physicochemical and toxicity parameters were predicted for the selected high binders and dapagliflozin. The stability and intermolecular interactions of high binders and dapagliflozin protein-ligand complexes were studied using molecular dynamics simulation.
RESULTS: The binding affinity ranges from -3.5 to -6.7 kcal × mol-1. Abietic acid and dehydroabietic acid had a higher binding affinity with a score of -6.7 kcal × mol-1, similar to the standard drug, dapagliflozin (-6.4 kcal × mol-1). Both abietic acid and dehydroabietic acid also have good bioavailability scores. MD simulation studies indicated greater stability for abietic acid-FOXO6 and dehydroabietic acid-FOXO6 complexes.
CONCLUSIONS: This investigation has shed light on the significance of the compounds of Z. officinale R. as potential FOXO6 inhibitors, which could further be used as a lead compound for developing alternative therapy for CKD.