Mechanism-based antidiabetic activity of Fructo- and isomalto-oligosaccharides: Validation by in vivo, in silico and in vitro interaction potential

• Aspergillus oryzae (MTCC5154) culture was conditioned to produce FOS.
• Out of FOSs, IMOs and FOS + IMO; FOS + IMO demonstrated better antidiabetic action in T2D rats.
• Nystose showed DPP-IV inhibition at IC50 = 146.8 μM.
• Panose at 20.2 μM showed 50% binding to PPAR-γ-LBD.
• Combination index of Nys25 + Pan25 were found to be 0.123.

This study evaluates the relative beneficial effects of 10% dietary intake of fructooligosaccharides (FOSs) and isomaltooligosaccharides (IMOs) and combination of FOS + IMO in poloxamer-407 (PX-407) induced type 2 diabetic Wistar rats. FOSs was produced from Aspergillus oryzae (MTCC5154) while IMOs and standards of 1-kestose, 1-nystose, 1-fructofuranosyl nystose and panose were procured. In silico docking studies were performed by GLIDE program for each of the FOSs and IMOs for PPAR-γ activation and DPP-IV inhibition. Diabetic rats treated with FOS + IMO showed relatively more amelioration of glycemic and lipid dysmetabolism, remarkable reduction in oxidative markers, increased GLP-1 content as well as Bifidobacteria/Lactobacilli population in caecum than lone FOSs/IMOs treatment. Out of nine oligosaccharides docked from FOS and IMO; panose, nystose and kestose showed highest ranking binding mode with DPP-IV and PPAR-γ and were selected for in vitro study either alone or in combinations. On its own nystose showed potent DPP-IV inhibitory activity with an IC50 of 146.8 μM while panose at 20.2 μM concentrations showed 50% binding ability to PPAR-γ-LBD. Combinations of oligosaccharides tested namely Nys + Pan, Nys + Kes and Pan + Kes demonstrated significant (p < 0.001) effect on PPAR-γ/DPP-IV bioassay. The results provide pharmacological evidence of FOSs and IMOs as antihyperglycemic mediated by their interaction with multiple targets operating in diabetes particularly nystose and pannose.

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