Polydatin ameliorates dextran sulfate sodium-induced colitis by decreasing oxidative stress and apoptosis partially via Sonic hedgehog signaling pathway.

Abstract

BACKGROUND:

Inflammation, oxidative stress and epithelial barrier dysfunction have been implicated in inflammatory bowel disease (IBD) pathology. The targeted inhibition of these features may represent a promising therapeutic strategy for IBD. Polydatin is an effective natural antioxidant that possesses strong antioxidant and anti-apoptotic properties. Thus, we studied the protective effects of polydatin treatments on a mouse model of experimental colitis.

METHODS:

Acute colitis was experimentally induced by adding 3% dextran sulfate sodium (DSS) to the drinking water provided to mice for 7 days and by administering different doses of polydatin (15, 30, or 45 mg/kg) during the same period. Mice were also treated with the Sonic hedgehog (Shh) pathway inhibitor cyclopamine to estimate the efficacy of polydatin and Shh inhibitors on colitis. The disease activity index (DAI), colon length, histology, levels of oxidative and apoptotic mediators and levels of Shh pathway components were evaluated.

RESULTS:

The polydatin treatment significantly attenuated the DAI, colon shortening and histological damage. In addition, polydatin administration effectively decreased malondialdehyde (MDA) levels and increased the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Polydatin also inhibited apoptosis in mice with colitis by downregulating the expression of the pro-apoptotic proteins Bax, caspase 3 and cleaved caspase 3 and increasing the expression of the anti-apoptotic protein Bcl-2. Furthermore, polydatin modulated Shh signaling pathway activation. After polydatin treatment, the main components of the Shh pathway, including Shh, Patched (Ptc), Smoothened (Smo), and glioblastoma-1 (Gli1), were upregulated at the mRNA and protein levels. Blockade of the Shh pathway using cyclopamine abolished the effects of polydatin on mice with colitis.

CONCLUSION:

Based on these observations, polydatin may suppress experimental colitis at least partially by regulating the Shh signaling pathway.

• Authors: Tingting Lv, Lei Shen, Lei Yang, Wenxiu Diao, Zhenming Yang, Ying Zhang, Shijie Yu, Yanxia Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 64 Pg. 256-263 (Nov 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30218952 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Glucosides
• Hedgehog Proteins
• Shh protein, mouse
• Stilbenes
• Dextran Sulfate
• polydatin

Topics

• Animals
• Apoptosis (drug effects)
• Colitis (chemically induced, drug therapy, metabolism)
• Dextran Sulfate
• Glucosides (pharmacology, therapeutic use)
• Hedgehog Proteins (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• Signal Transduction (drug effects)
• Stilbenes (pharmacology, therapeutic use)