Antidiabetic activity and molecular docking of fructooligosaccharides produced by Aureobasidium pullulans in poloxamer-407-induced T2DM rats.

This study evaluated the beneficial effects of fructooligosaccharide (FOS) intake from Aureobasidium pullulans using poloxamer-407 (PX-407) induced type 2 diabetes mellitus (T2DM) in rat. Administration of FOS enhanced enzymatic activities of catalase and glutathione reductase in a dose-dependent manner. Significant reduction in fasting plasma triacylglycerol and very low-density lipoprotein level coupled with slight increase in fasting plasma insulin level was observed. Significant decrease in severe glucosuria, proteinuria, blood creatinine, urea and advanced glycation end products was also observed. Supplementation of FOS increased glucagon like peptide-1 content as well as Bifidobacteria and Lactobacilli populations in the caecum. Molecular docking by Gold and Glide software revealed that three sugar types present in the FOS (1-kestose, nystose, and 1-ß-fructofuranosyl nystose) are potent dipeptidyl peptidase-IV inhibitors as well as peroxisome proliferator-activated receptor-gamma agonists. This work indicates that FOS can be positioned as a nutraceutical product, beneficial in diabetes-associated metabolic abnormalities.

Antihyperglycemic activity with DPP-IV inhibition of alkaloids from seed extract of Castanospermum australe: Investigation by experimental validation and molecular docking.

The antidiabetic actions of Castanospermum australe Cunn., seed (CAS) extract were evaluated in Poloxamer-407 (PX-407) induced T2DM rats. The CAS extract (100 and 150 mg/kg body weight) was administered orally once a day for 5 weeks after the animals were confirmed diabetic. A significant increase in blood glucose, HbA1c and serum insulin levels were observed in T2DM rats in comparison to citrate control rats. Treatment with CAS extract in T2DM rats reduced the elevated levels of blood glucose, HbA1c and insulin with significant (p≤0.001) improvement in OGT. The CAS extract treatment also increased (p≤0.001) the K(ITT) and prevented increase in HOMA-R level in T2DM rats. The DPP-IV inhibitory potential of CAS extract showed IC50 value of 13.96 µg/ml whilst the standard Diprotin A displayed the IC50 value of 1.543 µg/ml. Molecular docking of the three reported alkaloids from the seeds of C. australe showed comparable DPP-IV inhibition with berberine. Our data suggest that CAS extract (150 mg/kg body weight) normalizes hyperglycemia in T2DM rats with strong DPP-IV inhibitory potential. The molecular docking showed that among the three alkaloids of seed extract 7-Deoxy-6-epi-castanospermine is a potent DPP-IV inhibitor similar to berberine.