Holarrhena pubescens (Kutaj) bark extract mitigates SDS-induced IBD-like pathologies in Drosophila melanogaster by preserving barrier integrity and antioxidant defense

Inflammatory bowel disease (IBD) is a group of chronic conditions characterized by relapsing inflammation of gastrointestinal tract. Conventional treatments for IBD are confronted with various challenges including treatment failure, a therapeutic ceiling that restricts effectiveness and associated adverse effects. Present study employed Drosophila melanogaster as a model organism to investigate the protective effect of Holarrhena pubescens Wall. ex G. Don (Kutaj) Bark Extract (HpBE) against sodium dodecyl sulfate (SDS)-induced IBD-like etiologies. Ultra-high performance liquid chromatography (UHPLC) identified Epigallocatechin (EGC), Epicatechin (EC) and Protocatechuic acid as key phytometabolites in HpBE. On LCMS/MS-TQ analysis, these phytometabolites were also detected in whole body lysates of Drosophila treated with HpBE, confirming their absorption. HpBE was tolerated well in Drosophila , enhanced survival and mitigated SDS-induced intestinal injury, as demonstrated by smurf and trypan blue dye exclusion assays. Importantly, treatment with HpBE improved feed uptake, restored excretory function and prevented weight loss. Notably, HpBE also prevented the general sickness associated with inflamed gut, as evident from enhanced climbing activity. SDS-exposed flies that received HpBE, exhibited enhanced antioxidant defence and preserved cytoskeletal integrity of gut, as evidenced by increased GSH levels, SOD activity and phalloidin staining. These effects of HpBE were found to be associated with the modulation in gene expression related to Wnt/β-Catenin and JAK-STAT signalling. Overall, present study underlines the protective potential of HpBE against SDS-induced IBD-like etiologies in D. melanogaster model, and lays a foundation for further research to correlate these findings with clinical observations.