In-silico exploration of Attukal Kizhangu L. compounds: Promising candidates for periodontitis treatment

Abstract

A medicinal pteridophyte known as Attukal Kizhangu L. has been used to cure patients for centuries by administering plant parts based on conventional and common practices. Regarding its biological functions, significant use and advancement have been made. Extract of Attukal Kizhangu L. is the subject of the current study, which uses network pharmacology as its foundation. Three targeted compounds such as α-Lapachone, Dihydrochalcone, and Piperine were chosen for additional research from the 17 Phytoconstituents that were filtered out by the Coupled UPLC-HRMS study since they followed to Lipinski rule and showed no toxicity. The pharmacokinetics and physicochemical properties of these targeted compounds were analyzed by using three online web servers pkCSM, Swiss ADME, and Protox-II. This is the first in silico study to document these compound's effectiveness against the standard drug DOX in treating Periodontitis. The Swiss target prediction database was used to retrieve the targets of these compounds. DisGeNET and GeneCards were used to extract the targets of periodontitis. The top five hub genes were identified by Cytoscape utilizing the protein-protein interaction of common genes, from which two hub genes and three binding proteins of collagenase enzymes were used for further studies AA2, PGE2, PI2, TNFA, and PGP. The minimal binding energy observed in molecular docking, indicative of the optimal docking score, corresponds to the highest affinity between the protein and ligand. To corroborate the findings of the docking study, molecular dynamics (MD) simulations, and MMPBSA calculations were conducted for the complexes involving AA2-α-LPHE, AA2-DHC, and AA2-PPR. This research concluded that AA2-DHC was the most stable complex among the investigated interactions, surpassing the stability of the other complexes examined in comparison with the standard drug DOX. Overall, the findings supported the promotion of widespread use of Attukal Kizhangu L. in clinics as a potential therapeutic agent or may be employed for the treatment of acute and chronic Periodontitis.