Network Pharmacology and Molecular Docking to Elucidate the Anti-Dermatitic Mechanism of Phytocompounds in Thespesia Populnea Flowers.

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by chronic inflammation, immune dysregulation, and compromised skin barrier function. Thespesia populnea is found to be a rich source of polyphenols and flavonoids and it provides various therapeutic applications in dermatology. The pharmacological action of phytocompounds present in the flower part of Thespesia populnea in treating the skin inflammation is largely unknown. In the present study, we have employed a network pharmacology and molecular docking approach to explore the therapeutic potential of Thespesia populnea in treating AD and to understand the molecular mechanism of action of phytocompounds present in the flower part of Thespesia populnea. The phytochemical data of Thespesia populnea were extracted from the IMPPAT database, which includes 16 phytocompounds: gossypol, kaempferol, quercetin, lupenone, lupeol, quercetin-3-glucoside, beta-sitosterol, etc. Based on the SEA database search, 226 targets were identified to have binding affinity with the phytocompounds present in Thespesia populnea flowers. A total of 1538 AD-associated targets were retrieved and out of which 71 were identified to be ligand-associated AD targets and were further used for network construction. The AD network revealed the multi-targeted mechanism of phytocompounds present in Thespesia populnea against AD targets responsible for its anti-dermatitic activity. The top 15 potential protein targets in the network were found to be AKT1, NFKB1, MMP9, STAT3, EGFR, BCL2, PPARG, ESR1, MMP2, IL2, TLR2, GSK3B, KDR, CREB1, and ALOX5. Based on virtual screening and SwissADME prediction, eight docking complexes with high binding affinity and favorable pharmacokinetic properties were selected for AutoDock analysis. Among the selected docking complexes, beta-sitosterol and glycogen synthase kinase-3 beta (GSK3B) complex were found to possess the maximum binding energy of -8.3 kcal/mol with interacting amino acids GLU B:290, PRO A:212, PRO B:286, and TYR B:288. Other potent interactions that signify the anti-dermatitic potential of Thespesia populnea include kaempferol-GSK3B, lupeol-GSK3B, beta-sitosterol-GSK3B, herbacetin-ALOX5, gossypetin-ALOX5, quercetin-ALOX5, lupenone-ALOX5, and lupeol-ALOX5. The GSK3B complex and arachidonate 5-lipoxygenase were found to be the key anti-dermatitic targets for the phytocompounds present in Thespesia populnea flowers. The network pharmacological study revealed the mechanism of action of the phytocompounds present in Thespesia populnea flowers against potential dermatitis targets and molecular docking analysis highlighted the potent interactions responsible for its anti-dermatitic property. The present study offers valuable insights into the anti-dermatitic property of Thespesia populnea flowers (Supporting information).