Abstract :
Background: chromium-D-phenylalanine [Cr(D-phe)3] is known to be anti-diabetic, anti-inflammatory
and antioxidant complex. Our preliminary work reveals the beneficial effect of Cr(D-phe)3 in indomethacininduced
enterocolitis.
Aim: The present work was intended to explore the effect of Cr(D-phe)3 in acetic acid-induced ulcerative
colitis in rats. Further, molecular docking simulation experiments were performed.
Methodology: Colitis was induced through intra-rectal instillation of acetic acid (3% v/v) and the
effectiveness of Cr(D-phe)3 (30, 60 and 90 mg/kg) and sulphasalazine was measured using clinical,
macroscopic, biochemical, contractility and histopathological studies. In addition, drug likeliness,
molecular docking and dynamic studies of Cr(D-phe)3 and sulphasalazine with NF-kappa B (1NFK) were
carried out.
Results: Pretreatment of different doses of Cr(D-phe)3 showed significant reduction (P
in clinical, macroscopic score, oxidative stress and elevated biochemical parameters. Protective nature of
Cr(D-phe)3was further confirmed by histopathological examination and colonic contractility studies. In
silico studies reveals that Cr(D-phe)3 exhibited better docking score (-14.121) compared to sulphasalazine
(-5.654). Dug likeliness studies showed that Cr(D-phe)3 passes lipinski’s rule and exhibited better
bioavailability properties with negligible hepatotoxicity compared to standard. Molecular dynamic studies
reveal that Cr(D-phe)3 showed better stability compared to standard compound, while interacting with
1NFK for 10 ns.
Conclusion: The observed beneficial activity of Cr(D-phe)3 could be due to its anti-oxidative and antiinflammation
by preventing NF-kB activity.
Keyword :
Inflammatory Bowel Disease, Cr(D-phe)3, Colonic contractility, Oxidative stress, Drug likeliness, 1NFK.