Abstract:
The chronic metabolic disorder known as diabetes mellitus severely deteriorates memory
function and learning while damaging hippocampal tissue. Given that impaired
hippocampal insulin signaling leads to memory deficits, insulin resistance and
hyperinsulinemia are considered critical links between type 2 diabetes mellitus (T2DM)
and AD. This study utilized streptozotocin (STZ)-induced diabetic rat model to evaluate
the therapeutic potential of indole propionate (IPA) and Shikonin as treatments for
cognitive impairment. Male albino rats were divided into seven groups, three control
groups receiving ddH₂O, IPA, and Shikonin, respectively, and four experimental groups
treated with a high-fat diet and intraperitoneal (IP) injections of STZ (25 mg/kg) to
induce diabetes. Following disease induction, diabetic rats were treated with IPA (40
mg/kg), Shikonin (10 mg/kg), and metformin (200 mg/kg) for 28 days. The study
measured three critical parameters which included body weight assessment together with
blood glucose levels and evaluation of hippocampal and cortical gene expression analysis
related to cognitive impairment. Real-time quantitative PCR (RT-qPCR) was utilized to
evaluate mRNA expression levels of genes implicated in these deficits. Our findings
demonstrate that the elevated expression of Tau and APP in diabetic rats was
substantially reduced with IPA treatment (p < 0.0001). Additionally, PDIA3 (ERp57), an
endoplasmic reticulum (ER)-resident chaperone, was significantly downregulated in the
T2DM group but restored with IPA treatment. Dysregulated expression of the
mitochondrial chaperone Hsp60 was also improved with both IPA and Shikonin. Insulindegrading enzyme (IDE), a key protein linking T2DM and AD, showed substantial
restoration in the T2DM+IPA-treated group. IPA and Shikonin treatments improved the
body weight and blood glucose levels of diabetic rats who experienced notable decreases
in both parameters initially. The results of the study demonstrate how IPA and Shikonin
show promise as treatments for reducing cognitive problems in diabetes patients.
However, the clinical deployment of these compounds needs confirmation through
additional studies at the cellular and molecular levels.
