ANTI-DIABETIC STUDIES OF Chromolena odrata FLAVONOID FRACTION IN STREPTOZOCIN-TREATED RATS: INVOLVEMENT OF TGR5/INSULIN/PDX 1 PATHWAY
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Date
2021-11-11
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Adekunle Ajasin University Akungba
Abstract
The results showed that CoF up-regulated the expression of insulin and pancreatic duodenal
homeobox-1 genes in the pancreas, and GLP-1 in the intestine. In the kidney, BUN/SC levels
were restored to pre-STZ treatment states following CoF treatment. Inflammatory and kidney
injury molecule -1 genes were equally significantly down-regulated (p<0.05) in STZ-CoF
treated group in comparison with STZ-only group. In the aorta, the significant increase of
inflammatory genes as a result of STZ treatment, were down-regulated by CoF intervention.
CoF also significantly increased antioxidant genes that were down-regulated in the STZ-only
group. Histo-structural alterations associated with STZ treatment were completely reversed in
STZ-CoF group in the pancreas, kidney and aorta. NOAEL experiments revealed that CoF is
relatively safe up to doses of 100 mg/kg b.w. Moleculardynamics simulation confirmed TGR5
as the putative target, where it evolved active state conformation from a starting intermediate
state conformation when bound to CoF. Further studies revealed that the performance ofCoF
was highly comparable with metformin (an anti-diabetic drug).